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Recent evidence demonstrated CIN4 as a predictive marker of anthracycline benefit in early breast cancer. An analysis of the NCIC CTG MA.21 clinical trial was performed to test the role of existing CIN gene expression signatures as prognostic and predictive markers in the context of taxane based chemotherapy.RNA was extracted from patients in cyclophosphamide, epirubicin and flurouracil (CEF) and epirubicin, cyclophosphamide and paclitaxel (EC/T) arms of the NCIC CTG MA.21 trial and analysed using NanoString technology.After multivariate analysis both high CIN25 and CIN70 score was significantly associated with an increased in RFS (HR 1.76, 95%CI 1.07-2.86, p=0.0018 and HR 1.59, 95%CI 1.12-2.25, p=0.0096 respectively). Patients whose tumours had low CIN4 gene expression scores were associated with an increase in RFS (HR: 0.64, 95% CI 0.39-1.03, p=0.06) when treated with EC/T compared to patients treated with CEF.In conclusion we have demonstrated CIN25 and CIN70 as prognostic markers in breast cancer and that CIN4 is a potential predictive maker of benefit from taxane treatment.

Chromosome instability (CIN) in solid tumours results in multiple numerical and structural chromosomal aberrations and is associated with poor prognosis in multiple tumour types. Recent evidence demonstrated CEP17 duplication, a CIN marker, is a predictive marker of anthracycline benefit. An analysis of the BR9601 and MA.5 clinical trials was performed to test the role of existing CIN gene expression signatures as predictive markers of anthracycline sensitivity in breast cancer. Univariate analysis demonstrated, high CIN25 expression score was associated with improved distant relapse free survival (DRFS) (HR: 0.74, 95% CI 0.54-0.99, p = 0.046). High tumour CIN70 and CIN25 scores were associated with aggressive clinicopathological phenotype and increased sensitivity to anthracycline therapy compared to low CIN scores. However, in a prospectively planned multivariate analysis only pathological grade, nodal status and tumour size were significant predictors of outcome for CIN25/CIN70. A limited gene signature was generated, patients with low tumour CIN4 scores benefited from anthracycline treatment significantly more than those with high CIN4 scores (HR 0.37, 95% CI 0.20-0.56, p = 0.001). In multivariate analyses the treatment by marker interaction for CIN4/anthracyclines demonstrated hazard ratio of 0.35 (95% CI 0.15-0.80, p = 0.012) for DRFS. This data shows CIN4 is independent predictor of anthracycline benefit for DRFS in breast cancer.

PurposeTo provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.MethodsPubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts.ResultsOf the 53 publications identified and reviewed, none prompted a change in the 2013 recommendations.RecommendationsMost hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

Background: The Quality Initiative in Rectal Cancer (QIRC) trial targeted surgeon intraoperative technique and not radiation therapy (RT) use. We performed a post hoc analysis of RT use among patients in the QIRC trial, not by arm of trial but rather for the entire group. We wished to identify associations between local recurrence risk and use of preoperative, postoperative or no RT Methods: We compared demographic, tumour and process of care measures among patients receiving preoperative, postoperative or no RT. A multivariable Cox regression model assessed local recurrence risk. Results: The QIRC trial enrolled 1015 patients at 16 hospitals between 2002 and 2004. Radiation therapy use did not differ between trial arms, and median follow-up was 3.6 years. For the preoperative, postoperative and no RT groups, respectively, the percentage of patients was 12.8%, 19.3% and 67.9%; the percentage of stage II/III tumours was 57.0%, 88.7% and 48.1%; and the local recurrence rate was 5.3%, 10.2% and 5.5% (p = 0.05). After controlling for patient and tumour characteristics, including tumour stage, the hazard ratio (HR) for local recurrence was increased in the postoperative RT versus the no RT group (HR 1.64, 95% confidence interval 1.04-2.58, p = 0.027). Conclusion: Use of preoperative RT was low; most patients with stage II/III disease did not receive RT and, as expected, the postoperative RT group had the highest risk of local recurrence. Our results suggest opportunities to improve rectal cancer RT use in Ontario. Contexte: L'essai QIRC (Quality Initiative in Rectal Cancer) portait sur la technique peroperatoire des chirurgiens et non sur l'utilisation de la radiotherapie (RT). Nous avons effectue une analyse retrospective de l'utilisation de la RT chez les patients inclus dans l'essai QIRC, non pas en fonction des differents groupes de l'essai, mais en fonction de sa population entiere. Nous avons voulu verifier les liens entre le risque de recurrences locales et l'utilisation preoperatoire ou postoperatoire de la RT ou l'abstention de toute RT. Methodes: Nous avons compare les parametres demographiques, les caracteristiques de la tumeur et le processus de soins chez les patients soumis a une RT preoperatoire ou postoperatoire, ou non traites par RT. Un modele de regression multivariee de Cox a permis d'evaluer le risque de recurrences locales. Resultats: L'essai QIRC a regroupe 1015 patients de 16 hopitaux entre 2002 et 2004. Le recours a la radiotherapie n'a pas differe entre les groupes de l'essai, et le suivi median a ete de 3,6 ans. Pour ce qui est des groupes soumis a une RT preoperatoire ou postoperatoire, ou non soumis a la RT, respectivement, le pourcentage de patients etait de 12,8 %, 19,3 % et 67,9 %; le pourcentage de tumeurs de stade II/III etait de 57,0 %, 88,7 % et 48,1 %, et le taux de recurrences locales, de 5,3 %, 10,2 % et 5,5 % (p = 0,05). Apres ajustement pour tenir compte des caracteristiques des patients et des tumeurs, y compris le stade de la tumeur, le risque relatif (RR) de recurrences locales a augmente dans le groupe soumis a une RT postoperatoire par rapport au groupe non soumis a la RT (RR 1,64; intervalle de confiance de 95 %, 1,04-2,58, p = 0,027). Conclusion: Le recours a la RT preoperatoire a ete faible; la plupart des patients atteints d'une maladie de stade II/III n'ont pas recu de RT et comme prevu, le groupe soumis a une RT postoperatoire a presente le risque le plus eleve de recurrences locales. Nos resultats indiquent qu'il serait possible d'ameliorer l'utilisation de la RT pour le cancer rectal en Ontario., A negative outcome following rectal cancer surgery is local tumour recurrence in the pelvis. Prospective randomized trials have demonstrated that pelvic radiation can reduce postsurgical rates of local recurrence and [...]

Background: Theory suggests the uptake of a medical innovation is influenced by how potential adopters perceive innovation characteristics and by characteristics of potential adopters. Innovation adoption is slow among the first 20% of individuals in a target group and then accelerates. The Quality Initiative in Rectal Cancer (QIRC) trial assessed if rectal cancer surgery outcomes could be improved through surgeon participation in the QIRC strategy. We tested if traditional uptake of innovation concepts applied to surgeons in the experimental arm of the trial. Methods: The QIRC strategy included workshops, access to opinion leaders, intraoperative demonstrations, postoperative questionnaires, and audit and feedback. For intraoperative demonstrations, a participating surgeon invited an outside surgeon to demonstrate optimal rectal surgery techniques. We used surgeon timing in a demonstration to differentiate early and late adopters of the QIRC strategy. Surgeons completed surveys on perceptions of the strategy and personal characteristics. Results: Nineteen of 56 surgeons (34%) requested an operative demonstration on their first case of rectal surgery. Early and late adopters had similar perceptions of the QIRC strategy and similar characteristics. Late adopters were less likely than early adopters to perceive an advantage for the surgical techniques promoted by the trial (p = 0.023). Conclusion: Most traditional diffusion of innovation concepts did not apply to surgeons in the QIRC trial, with the exception of the importance of perceptions of comparative advantage. Contexte: Selon une theorie, 2 facteurs influencent l'adoption de nouvelles pratiques en medecine, soit la facon dont les adeptes potentiels percoivent les caracteristiques novatrices et les caracteristiques propres aux adeptes potentiels eux-memes. L'adoption des nouvelles pratiques se fait lentement chez les premiers 20 % des individus d'un groupe cible, puis va en s'accelerant. L'etude QIRC (Quality Initiative in Rectal Cancer) a voulu verifier si la participation des chirurgiens a la strategie QIRC pouvait ameliorer l'issue de la chirurgie pour cancer du rectum. Nous avons verifie si les modes habituels d'adoption des nouvelles pratiques s'appliquaient aux chirurgiens dans le groupe experimental de l'etude. Methodes: La strategie QIRC incluait des ateliers, l'acces a des meneurs d'opinion, des demonstrations peroperatoires et des questionnaires postoperatoires, suivis de verifications et de commentaires. Pour les demonstrations peroperatoires, un chirurgien participant invitait un chirurgien de l'exterieur a faire une demonstration de techniques chirurgicales rectales optimales. Nous avons utilise les delais d'adoption des nouvelles pratiques par les chirurgiens pour faire ressortir la distinction entre les adeptes precoces et tardifs de la strategie QIRC. Les chirurgiens ont repondu a des questionnaires sur leurs perceptions a l'endroit de la strategie et sur leurs caracteristiques personnelles. Resultats: Dix-neuf chirurgiens sur 56 (34 %) ont demande une demonstration operatoire lors de leur premier cas de chirurgie rectale. Les adeptes precoces et tardifs avaient des perceptions similaires de la strategie QIRC et des caracteristiques personnelles similaires. Les adeptes tardifs etaient moins susceptibles que les adeptes precoces de percevoir l'avantage des techniques chirurgicales preconisees dans le cadre de l'etude (p= 0,023). Conclusion: La plupart des modes habituels de diffusion des nouvelles pratiques ne s'appliquaient pas aux chirurgiens de l'essai QIRC, a l'exception de l'importance des perceptions a l'endroit des avantages comparatifs., Researchers suggest that the uptake of a medical innovation depends on how potential adopters perceive the characteristics of the innovation, the characteristics of the potential adopters and contextual factors that [...]

The study attempts to evaluate and compare the efficacy of a 3-week schedule of hypofractionated radiation therapy as against a 5-week schedule for treatment of breast cancer. The results indicate that there was no difference in efficacy between the two following ten years of treatment.

Background: There has been minimal research on the influence of delays for cancer treatments on patient outcomes. We measured the influence of delays to nonemergent colon cancer surgery on operative mortality, disease-specific survival and overall survival. Methods: We used the linked Surveillance, Epidemiology and End Results (SEER)-Medicare databases (1993-1996) to identify patients who underwent nonemergent colon cancer surgery. We assessed 2 time intervals: surgeon consult to hospital admission for surgery and first diagnostic test for colon cancer to hospital admission. Follow-up data were available to the end of 2003. We selected the time intervals to create patient groups with clinical relevance and they did not extend past 120 days. Results: We identified 7989 patients who underwent nonemergent colon cancer surgery. Median delays from surgeon consult to admission and from first diagnostic test to admission were 7 and 17 days, respectively. The odds of operative mortality were similar if the consult-to-admission interval was 22 days or more versus 1-7 days (odds ratio [OR] 1.0, 95% confidence interval [CI] 0.6-1.8, p = 0.91) or if the test-to-admission interval was 43 days or more versus 1-14 days (OR 0.8, 95% CI 0.4-1.5, p = 0.51), respectively. For these same respective interval comparisons, disease-specific survival was not influenced by the consult-to-admission wait (hazard ratio [HR] 1.0, 95% CI 0.9-1.2, p = 0.91) or the test-to-admission wait (HR 1.0, 95% CI 0.8-1.1, p = 0.63). The risk of death was slightly greater if the consult-to-admission interval was 22 or more days versus 1-7 days (HR 1.1, 95% CI 1.0-1.2, p = 0.013) and if the test-to-admission interval was 43 days or more versus 1-14 days (HR 1.2, 95% CI 1.1-1.3, p = 0.003). Conclusion: It is unlikely that delays to nonemergent colon cancer surgery longer than 3 weeks from initial surgical consult or longer than 6 weeks from first diagnostic test negatively impact operative mortality, disease-specific survival or overall survival. Contexte : Quelle influence le retard de traitement du cancer a-t-il sur le pronostic des patients? Peu de recherches ont porte sur cette question. Nous avons voulu mesurer l'influence du retard a operer les cas de cancer du colon juges non urgents sur la mortalite operatoire, la survie specifique a la maladie et la survie globale. Methodes : Nous avons utilise les bases de donnees reliees Medicare-SEER (Surveillance, Epidemiology and End Results) de 1993 a 1996 afin de recenser les patients ayant subi une chirurgie non urgente pour cancer du colon. Nous avons evalue 2 intervalles : soit le temps ecoule entre la consultation du chirurgien et l'hospitalisation pour chirurgie et le temps ecoule entre le premier test diagnostique pour cancer du colon et l'hospitalisation. Nous disposions de donnees de suivi s'echelonnant jusqu'a la fin de 2003. Nous avons selectionne les intervalles de facon a creer des groupes de patients cliniquement pertinents et ces intervalles ne depassaient pas 120 jours. Resultats : Nous avons recense 7989 patients qui ont subi une chirurgie non urgente pour cancer du colon. Les delais medians entre la consultation du chirurgien et l'hospitalisation et entre le premier test diagnostique et l'hospitalisation ont ete respectivement de 7 et 17 jours. Le risque de mortalite operatoire etait semblable si l'intervalle entre la consultation et l'hospitalisation etait de 22 jours ou plus c. 1 a 7 jours (rapport des cotes [RC] 1,0; intervalle de confiance [IC] a 95 %, 0,6-1,8, p = 0,91) ou si l'intervalle entre le premier test diagnostique et l'hospitalisation etait de 43 jours ou plus c. 1 a 14 jours (RC 0,8; IC a 95 %, 0,4-1,5, p = 0,51), respectivement. Pour ces memes comparaisons d'intervalles respectifs, la survie specifique a la maladie n'a pas ete affectee par le delai entre la consultation et l'hospitalisation (risque relatif [RR] 1,0; IC a 95 %, 0,9-1,2, p = 0,91) ni par le delai entre le premier test diagnostique et l'hospitalisation (RR 1,0; IC a 95 %, 0,8-1,1, p = 0,63). Un intervalle entre la consultation et l'hospitalisation de 22 jours ou plus plutot que de 1 a 7 jours (RR 1,1; IC a 95 % 1,0-1,2, p = 0,013) et un intervalle entre le premier test diagnostique et l'hospitalisation de 43 jours ou plus plutot que de 1 a 14 jours (RR 1,2; IC a 95 %, 1,1-1,3, p = 0,003) etaient associes a un risque global de deces legerement superieur. Conclusion : Il semble peu probable que les retards de plus de 3 semaines avant une chirurgie non urgente pour un cancer du colon a compter de la consultation avec le chirurgien, ou de plus de 6 semaines a compter du premier test diagnostique, aient un impact negatif sur le risque de mortalite operatoire, sur la survie specifique a la mala--die ou sur la survie globale., Lengthy waits for cancer services may harm patients by causing psychological distress (1-3) or lessening the effectiveness of treatments. (4-7) Waiting times for surgery are of particular relevance since surgical [...]

Objective: We sought to assess whether the specialty of the surgeon or the hospital involved in the initial management of women with ovarian cancer determined the likelihood of unnecessary repeated [...]

Formalin-fixed, paraffin-embedded specimens from patients enrolled in Mammary.5 (MA.5) randomized trial are studied to determine whether amplification of human epidermal growth factor receptor type 2 (HER2), overexpression of HER2, or both in breast-cancer cells identifies women who could benefit from cyclophosphosphamide, epirubicin and fluorouracil (CEF), as compared with cyclophosphamide, methotrexate and fluorouracil (CMF). The results have shown that amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracyckine-containing chemotherapy.