Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

Trimodal therapy for invasive bladder cancer: is it really equal to radical cystectomy?

PURPOSE OF REVIEW: Trimodal therapy (TMT) is considered the most effective bladder-sparing approach for muscle-invasive urothelial carcinoma of the bladder (MIBC) and an alternative to radical cystectomy. The purpose of this article was to review and summarize the current knowledge on the equivalence of TMT and radical cystectomy based on the recent literature. RECENT FINDINGS: TMT consists of a maximal transuretral resection of the bladder, followed by a concurrent radiotherapy and chemotherapy, limiting salvage radical cystectomy to nonresponder tumors or muscle-invasive recurrence. In large population studies, less than 6% of the patients with nonmetastatic MIBC receive a chemoradiation therapy and this rate is stable. A growing body of evidence exists that TMT provides good oncologic outcomes with low morbidity when compared with radical cystectomy. TMT requires, however, a close follow-up because of the high risk of local recurrence and salvage radical cystectomy in up to 30% of the patients. Salvage radical cystectomy can be performed with adequate results but does not offer the same opportunity of reconstruction and functional outcomes than primary radical cystectomy. SUMMARY: Although radical cystectomy is still the treatment of reference for most of the patients with localized MIBC, TMT represents a reasonable alternative in highly selected patients. Any firm conclusion on the equivalence or superiority of one treatment to the other is still limited by the lack of randomized controlled trials and the heterogeneity of the available literature. Future studies and multidisciplinary approach are mandatory to optimize the patient selection and regimen of TMT.

Nouveautés et perspectives dans la prise en charge des cancers colorectaux et gastriques avancés [News and perspectives in the treatment of advanced gastric and colorectal cancers].

Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future.

International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus.

BACKGROUND: Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2011, the first German expert consensus guideline defined the evidence for diagnosis and treatment of early and locally advanced esophagogastric cancers. Here, we compare this guideline with other national guidelines as well as current literature. METHODS: The German S3-guideline used an approved development process with de novo literature research, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were compared with German recommendations. RESULTS: In the German S3 and other Western guidelines, adenocarcinomas of the esophagogastric junction (AEG) are classified according to formerly defined AEG I-III subgroups due to the high surgical impact. To stage local disease, computed tomography of the chest and abdomen and endosonography are reinforced. In contrast, laparoscopy is optional for staging. Mucosal cancers (T1a) should be endoscopically resected "en-bloc" to allow complete histological evaluation of lateral and basal margins. For locally advanced cancers of the stomach or esophagogastric junction (≥T3N+), preferred treatment is preoperative and postoperative chemotherapy. Preoperative radiochemotherapy is an evidence-based alternative for large AEG type I-II tumors (≥T3N+). Additionally, some experts recommend treating T2 tumors with a similar approach, mainly because pretherapeutic staging is often considered to be unreliable. CONCLUSIONS: The German S3 guideline represents an up-to-date European position with regard to diagnosis, staging, and treatment recommendations for patients with locally advanced esophagogastric cancer. Effects of perioperative chemotherapy versus chemoradiotherapy are still to be investigated for adenocarcinoma of the cardia and the lower esophagus.

Arterial Therapies of Non-Colorectal Liver Metastases.

BACKGROUND: The unique situation of the liver with arterial and venous blood supply and the dependency of the tumor on the arterial blood flow make this organ an ideal target for intrahepatic catheter-based therapies. Main forms of treatment are classical bland embolization (TAE) cutting the blood flow to the tumors, chemoembolization (TACE) inducing high chemotherapy concentration in tumors, and radioembolization (TARE) without embolizing effect but very high local radiation. These different forms of therapies are used in different centers with different protocols. This overview summarizes the different forms of treatment, their indications and protocols, possible side effects, and available data in patients with non-colorectal liver tumors. METHODS: A research in PubMed was performed. Mainly clinical controlled trials were reviewed. The search terms were 'embolization liver', 'TAE', 'chemoembolization liver', 'TACE', 'radioembolization liver', and 'TARE' as well as 'chemosaturation' and 'TACP' in the indications 'breast cancer', 'neuroendocrine', and 'melanoma'. All reported studies were analyzed for impact and reported according to their clinical relevance. RESULTS: The main search criteria revealed the following results: 'embolization liver + breast cancer', 122 results, subgroup clinical trials 16; 'chemoembolization liver + breast cancer', 62 results, subgroup clinical trials 11; 'radioembolization liver + breast cancer', 37 results, subgroup clinical trials 3; 'embolization liver + neuroendocrine', 283 results, subgroup clinical trials 20; 'chemoembolization liver + neuroendocrine', 202 results, subgroup clinical trials 9; 'radioembolization liver + neuroendocrine', 64 results, subgroup clinical trials 9; 'embolization liver + melanoma', 79 results, subgroup clinical trials 15; 'chemoembolization liver + melanoma', 60 results, subgroup clinical trials 14; 'radioembolization liver + melanoma', 18 results, subgroup clinical trials 3. The term 'chemosaturation liver' was tested without indication since only few publications exist and provided us with five results and only one clinical trial. CONCLUSION: Despite many years of clinical use and documented efficacy on intra-arterial treatments of the liver, there are still only a few prospective multicenter trials with many different protocols. To guarantee the future use of these efficacious therapies, especially in the light of many systemic or surgical therapies in the treatment of non-colorectal liver metastases, further large randomized trials and transparent guidelines need to be established.

Prévention et dépistage du cancer en Suisse : fréquence et déterminants

Contexte : Après les maladies cardiovasculaires, le cancer est la deuxième cause de mortalité en Suisse. Les cancers de la prostate, du sein, du côlon-rectum, du col utérin et le mélanome cutané représentent, en termes d'incidence et de mortalité, la moitié du fardeau du cancer en Suisse. Des moyens de prévention primaire et/ou secondaire contribuent à réduire la fréquence et la mortalité due à ces cinq cancers. Cependant, l'attitude face à la prévention diffère selon les individus et dépend de multiples facteurs socio-économiques, environnementaux, culturels et comportementaux. Objectif : Évaluer la fréquence et identifier les déterminants des pratiques de dépistage des cancers de la prostate, du sein, du côlon-rectum, du col utérin et du mélanome cutané en Suisse. Matériel et méthode : Les données utilisées sont issues de l'Enquête suisse sur la santé 2007. Une pondération statistique permet d'extrapoler les résultats à la population générale. Des modèles de régression logistique multivariée ont été construits afin de décrire l'association entre pratique du dépistage et facteurs sociodémographiques, style de vie, état de santé, recours aux prestations de santé et soutien social. Résultats : En 2007, selon les méthodes et fréquences recommandées en Suisse et dans les tranches d'âge concernées, 49% des hommes ont effectué un dépistage du cancer prostatique, 13% du cancer colorectal et 33,7% du mélanome cutané. Chez les femmes, 17,9% ont réalisé un dépistage du cancer du sein, 8,7% du cancer colorectal, 36,8% du mélanome cutané et 50,2% du cancer du col utérin. Globalement et pour les deux sexes, l'âge, le lieu de résidence, le niveau de formation, la classe socioprofessionnelle, le revenu d'équivalence du ménage, la pratique d'autres dépistages des cancers, le nombre de visites médicales et de jours d'hospitalisation au cours des 12 mois précédents déterminent le recours au dépistage des cancers d'intérêt. Chez les hommes, la présence d'un médecin de famille et, chez les femmes, la franchise annuelle, influencent aussi la pratique du dépistage. Conclusion : Les prévalences du dépistage varient notablement selon le type de cancer. Le recours aux dépistages des cancers dépend de facteurs sociodémographiques, de l'utilisation des services de santé et de la pratique d'autres dépistages, mais peu, voire pas, du style de vie, de l'état de santé et de la sécurité et du soutien sociaux. Les facteurs identifiés sont souvent communs aux différents types de cancer et rendent possible l'établissement d'un profil général d'utilisateurs du dépistage des cancers. Les stratégies visant à améliorer la compliance aux examens de dépistage devraient considérer les facteurs qui en déterminent le recours et mieux cibler les segments de la population qui les sous-utilisent.

Role of ErbB2 and ErbB4 in Cancer Growth, Prognosis and as Targets for Immunotherapy

ErbB receptors (EGFR, ErbB2, ErbB3 and ErbB4) are growth factor receptors that regulate signals of cell differentiation, proliferation, migration and survival. Inappropriate activation of these receptors is associated with the development and severity of many cancers and has prognostic and predictive value in cancer therapy. Drugs, such as therapeutic antibodies, targeted against EGFR and ErbB2, are currently used in therapy of breast, colorectal and head and neck cancers. The role of ErbB4 in tumorigenesis has remained relatively poorly understood. Alternative splicing produces four different isoforms of one ErbB4 gene. These isoforms (JM-a, JM-b, CYT-1 and CYT-2) are functionally dissimilar and proposed to have different roles in carcinogenesis. The juxtamembrane form JM-a undergoes regulated intramembrane proteolysis producing a soluble receptor ectodomain and an intracellular domain that translocates into the nucleus and regulates transcription. Nuclear signaling via JM-a isoform stimulates cancer cell proliferation. This study aimed to develop antibodies targeting the proposed oncogenic ErbB4 JM-a isoform that show potential in inhibiting ErbB4 dependent tumorigenesis. Also, the clinical relevance of ErbB4 shedding in cancer was studied. The currently used monoclonal antibody trastuzumab, targeting ErbB2, has shown efficacy in breast cancer therapy. In this study novel tissues with ErbB2 amplification and trastuzumab sensitivity were analyzed. The results of this study indicated that a subpopulation of breast cancer patients demonstrate increased shedding and cleavage of ErbB4. A JM-a isoform-specific antibody that inhibited ErbB4 shedding and consequent activation of ErbB4 had anti-tumor activity both in vitro and in vivo. Thus, ErbB4 shedding associates with tumor growth and specific targeting of the cleavable JM-a isoform could be considered as a strategy for developing novel ErbB-based cancer drugs. In addition, it was demonstrated that ErbB2 amplification is common in intestinal type gastric cancers with poor clinical outcome. Trastuzumab inhibited growth of gastric and breast cancer cells with equal efficacy. Thus, ErbB2 may be a useful target in gastric cancer.

Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer

We determined the effect of long-term aerobic swimming training regimens of different intensities on colonic carcinogenesis in rats. Male Wistar rats (11 weeks old) were given 4 subcutaneous injections (40 mg/kg body weight each) of 1,2-dimethyl-hydrazine (DMH, dissolved in 0.9% NaCl containing 1.5% EDTA, pH 6.5), at 3-day intervals and divided into three exercise groups that swam with 0% body weight (EG1, N = 11), 2% body weight (EG2, N = 11), and 4% body weight of load (EG3, N = 10), 20 min/day, 5 days/week for 35 weeks, and one sedentary control group (CG, N = 10). At sacrifice, the colon was removed and counted for tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat was weighed. The mean number of aberrant crypt foci was reduced only for EG2 compared to CG (26.21 ± 2.99 vs 36.40 ± 1.53 crypts; P < 0.05). Tumor incidence was not significantly different among groups (CG: 90%; EG1: 72.7%; EG2: 90%; EG3: 80%). Swimming training did not affect either tumor multiplicity (CG: 2.30 ± 0.58; EG1: 2.09 ± 0.44; EG2: 1.27 ± 0.19; EG3: 1.50 ± 0.48 tumors) or size (CG: 1.78 ± 0.24; EG1: 1.81 ± 0.14; EG2: 1.55 ± 0.21; EG3: 2.17 ± 0.22 cm³). Intra-abdominal fat was not significantly different among groups (CG: 10.54 ± 2.73; EG1: 6.12 ± 1.15; EG2: 7.85 ± 1.24; EG3: 5.11 ± 0.74 g). Aerobic swimming training with 2% body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

Decision analysis of the effectiveness of lung cancer screening using autofluorescence bronchoscopy and computed tomography

Background: Lung cancer (LC) is the leading cause of cancer death in the developed world. Most cancers are associated with tobacco smoking. A primary hope for reducing lung cancer has been prevention of smoking and successful smoking cessation programs. To date, these programs have not been as successful as anticipated. Objective: The aim of the current study was to evaluate whether lung cancer screening combining low dose computed tomography with autofluorescence bronchoscopy (combined CT & AFB) is superior to CT or AFB screening alone in improving lung cancer specific survival. In addition, the extent of improvement and ideal conditions for combined CT & AFB screening were evaluated. Methods: We applied decision analysis and Monte Carlo simulation modeling using TreeAge Software to evaluate our study aims. Histology- and stage specific probabilities of lung cancer 5-year survival proportions were taken from Surveillance and Epidemiologic End Results (SEER) Registry data. Screeningassociated data was taken from the US NCI Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), National Lung Screening Trial (NLST), and US NCI Lung Screening Study (LSS), other relevant published data and expert opinion. Results: Decision Analysis - Combined CT and AFB was the best approach at Improving 5-year survival (Overall Expected Survival (OES) in the entire screened population was 0.9863) and in lung cancer patients only (Lung Cancer Specific Expected Survival (LOSES) was 0.3256). Combined screening was slightly better than CT screening alone (OES = 0.9859; LCSES = 0.2966), and substantially better than AFB screening alone (OES = 0.9842; LCSES = 0.2124), which was considerably better than no screening (OES = 0.9829; LCSES = 0.1445). Monte Carlo simulation modeling revealed that expected survival in the screened population and lung cancer patients is highest when screened using CT and combined CT and AFB. CT alone and combined screening was substantially better than AFB screening alone or no screening. For LCSES, combined CT and AFB screening is significantly better than CT alone (0.3126 vs. 0.2938, p< 0.0001). Conclusions: Overall, these analyses suggest that combined CT and AFB is slightly better than CT alone at improving lung cancer survival, and both approaches are substantially better than AFB screening alone or no screening.

Associations Between Personal Cancer History and Lung Cancer Risk

The study aim was to investigate the relationship between factors related to personal cancer history and lung cancer risk as well as assess their predictive utility. Characteristics of interest included the number, anatomical site(s), and age of onset of previous cancer(s). Data from the Prostate, Lung, Colorectal and Ovarian Screening (PLCO) Cancer Screening Trial (N = 154,901) and National Lung Screening Trial (N = 53,452) were analysed. Logistic regression models were used to assess the relationships between each variable of interest and 6-year lung cancer risk. Predictive utility was assessed through changes in area-under-the-curve (AUC) after substitution into the PLCOall2014 lung cancer risk prediction model. Previous lung, uterine and oral cancers were strongly and significantly associated with elevated 6-year lung cancer risk after controlling for confounders. None of these refined measures of personal cancer history offered more predictive utility than the simple (yes/no) measure already included in the PLCOall2014 model.

Predicting the Risk of Lung Cancer in Never-smokers

Despite being considered a disease of smokers, approximately 10-15% of lung cancer cases occur in never-smokers. Lung cancer risk prediction models have demonstrated excellent ability to discriminate cases from non-cases, and have been shown to be more efficient at selecting individuals for future screening than current criteria. Existing models have primarily been developed in populations of smokers, thus there was a need to develop an accurate model in never-smokers. This study focused on developing and validating a model using never-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cox regression analysis, with six-year follow-up, was used for model building. Predictors included: age, body mass index, education level, personal history of cancer, family history of lung cancer, previous chest X-ray, and secondhand smoke exposure. This model achieved fair discrimination (optimism corrected c-statistic = 0.6645) and good calibration. This represents an improvement on existing neversmoker models, but is not suitable for individual-level risk prediction.

Prévalence du VPH dans le cancer ORL localement avancé et impact sur le pronostic et l'efficacité de la chimio-radiothérapie concomitante

Problématique : Bien que le tabac et l’alcool soient les facteurs causaux principaux des cancers épidermoïdes de l’oropharynx, le virus du papillome humain (VPH) serait responsable de l’augmentation récente de l’incidence de ces cancers, particulièrement chez les patients jeunes et/ou non-fumeurs. La prévalence du VPH à haut risque, essentiellement de type 16, est passée de 20% à plus de 60% au cours des vingt dernières années. Certaines études indiquent que les cancers VPH-positifs ont un meilleur pronostic que les VPH- négatifs, mais des données prospectives à cet égard sont rares dans la littérature, surtout pour les études de phase III avec stratification basée sur les risques. Hypothèses et objectifs : Il est présumé que la présence du VPH est un facteur de bon pronostic. L’étude vise à documenter la prévalence du VPH dans les cancers de l’oropharynx, et à établir son impact sur le pronostic, chez des patients traités avec un schéma thérapeutique incluant la chimio-radiothérapie. Méthodologie : Les tumeurs proviennent de cas traités au CHUM pour des cancers épidermoïdes de la sphère ORL à un stade localement avancé (III, IVA et IVB). Elles sont conservées dans une banque tumorale, et les données cliniques sur l’efficacité du traitement et les effets secondaires, recueillies prospectivement. La présence du VPH est établie par biologie moléculaire déterminant la présence du génome VPH et son génotype. Résultats: 255 spécimens ont été soumis au test de génotypage Linear Array HPV. Après amplification par PCR, de l’ADN viral a été détecté dans 175 (68.6%) échantillons tumoraux ; le VPH de type 16 était impliqué dans 133 cas (52.25 %). Conclusion: Une proportion grandissante de cancers ORL est liée au VPH. Notre étude confirme que la présence du VPH est fortement associée à une amélioration du pronostic chez les patients atteints de cancers ORL traités par chimio-radiothérapie, et devrait être un facteur de stratification dans les essais cliniques comprenant des cas de cancers ORL.

Probiotics and cancer: from in vitro to human studies

Studies in cell cultures and animal models provide evidence that probiotics can beneficially influence various stages in development of colon cancer including tumor initiation, promotion and metastasis. For example, oral administration of Lactobacillus and Bifidobacterium strains can prevent genotoxic damage to the colonic epithelium (considered to be an early stage of the carcinogenic process). Administration to rats of probiotics reduced the incidence of carcinogen-induced pre-cancerous lesions (aberrant crypt foci) in the colon. Furthermore a combination of Bifidobacterium longum and inulin (a prebiotic) was more effective than either treatment alone. In this latter study, the dietary treatments were given after exposure to the carcinogen, which suggests that the protective effects were being exerted at the promotional phase of carcinogenesis. L. acidophilus feeding has been shown to decrease the incidence of colon tumors in rats challenged with a carcinogen and B. longum reduced the incidence of carcinogeninduced colon, liver and mammary tumors. There is limited evidence from epidemiological studies for protective effects of products containing probiotics in humans, but a number of recent dietary intervention studies in healthy subjects and in polyp and cancer patients have yielded promising results on the basis of biomarkers of cancer risk and grade of colorectal tumors.

A comparison of the anticancer properties of isoxanthohumol and 8-prenylnaringenin using in vitro models of colon cancer

The hops plant (Humulus lupulus L.) is an essential ingredient in beer and contains a number of potentially bioactive prenylflavonoids, the predominant being the weakly estrogenic isoxanthohumol (Ix), which can be converted to the more strongly estrogenic 8-PN by the colonic microbiota. The aim of this study was to investigate the biological activity of 8-PN and Ix using in vitro models representing key stages of colorectal carcinogenesis, namely cell growth and viability (MTT assay), cell-cycle progression (DNA content assay), DNA damage (Comet assay), and invasion (Matrigel assay). A significant decrease in Caco-2 cell viability was noted after both 8-PN and Ix treatments at the higher doses (40 and 50 μM, respectively) although the impact on cell cycle differed between the two compounds. The decreased cell viability observed after Ix treatment was associated with a concentration-dependent increase in G2/M and an increased sub-G1 cell-cycle fraction, whereas treatment with 8-PN was associated with an elevated G0/G1 and an increased sub-G1 cell-cycle fraction. Significant antigenotoxic activity was noted at all 8-PN concentrations tested (5-40 μM). Although significant antigenotoxic activity was also noted with Ix treatment at ≤25 μM, at a higher dose, Ix itself exerted genotoxic activity. In a dose-dependent manner, both compounds inhibited HT115 cell invasion with reductions up to 52 and 46% for Ix and 8-PN, respectively, in comparison to untreated cells. This study demonstrated that both Ix and its gut microbial metabolite 8-PN exert anticancer effects on models of key stages of colon tumourigenesis.