Search

Background This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). Methods In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. Results The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. Conclusions The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation.

Background Primary leiomyosarcoma (LMS) of the gastrointestinal (GI) tract is rare. Limited literature exists regarding the clinical characteristics and outcome for patients with localised and metastatic disease. Methods A retrospective chart review was performed for patients greater than 18 years of age diagnosed with GI LMS at The Royal Marsden Hospital between 1 January 2000–1 May 2020. Descriptive statistics were performed. Patients were censored at data cut-off date of 27 June 2020. Results Forty-six patients with a median age at diagnosis of 54 years (range 25–85) were identified. Fifteen percent (n = 7) of patients previously received abdominal radiation for an unrelated cancer. All patients with localised disease (n = 36) had resection with oncological margins. For patients who underwent potentially curative surgery, median recurrence-free survival (mRFS) was 13 months (0.4–183 months), and half of these patients (n = 18) developed recurrent disease post resection (distant n = 16, local n = 2). Median overall survival (mOS) was 27 months for patients with distant recurrence. Twenty-one percent (n = 10) of patients presented with synchronous metastatic disease and their mOS was 19 months. Median progression-free survival (mPFS) for patients treated with conventional chemotherapy ranged from 2.0 to 8.0 months. Conclusion The risk of recurrence is significant, and recurrence-free survival was short even with complete oncologic resection. The relationship of prior abdominal radiotherapy to the development of GI LMS warrants further investigation. Outcomes with systemic therapy for metastatic disease were poor and there is a need for the development of more effective systemic therapies.

Administration of chemotherapy before breast surgery has the potential to reduce the risk of distant recurrence by targeting micrometastasis as well as allowing a more minimalistic approach to surgical intervention. We performed a systematic review to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT).The primary outcome was to determine whether the timing of surgery post NACT impacted overall survival (OS) and disease-free survival (DFS). We compared patient outcomes between those who had surgery within 8 weeks of completion of NACT to those that had surgery after 8 weeks. An outcome comparison between4 weeks and 4-8 weeks was also performed. Secondary outcome included complete pathological response (pCR) post NACT. A meta-analysis was performed using the Mantel-Haenszel method.Five studies, including 8794 patients were eligible for inclusion. Patients that had surgery within 8 weeks of completion of NACT had a statistically significant improved OS(OR 0.47, 95% c. i 0.34-0.65) and DFS(OR 0.71 (95% c. i 0.52-0.98, P = 0.04). There were no survival advantages associated with having surgery less than 4 weeks post completion of NACT (OR 0.78, 95% c. i 0.46-1.33, P = 0.37). There was no difference in pCR rate between those that had surgery4 weeks and 4-8 weeks (OR 1.01, 95% c. i 0.80-1.28, P = 0.93).This meta-analysis shows that the optimum timing of surgery post completion of NACT is 4-8 weeks as it is associated with increased OS and DFS.

Background No consensus exists regarding adequacy of margins after mastectomy. To determine if pathological margin proximity is associated with local (LR) or distant recurrence after mastectomy for early invasive breast cancer or ductal carcinoma in situ. Methods A systematic review of literature published from 1980 to 2019 and meta-analysis was conducted. Unpublished data were sought from authors (PROSPERO (CRD42019127541)). Thirty-four studies comprising 34,833 breast cancer patients were included in the quantitative synthesis. Eligible studies reported on patients undergoing curative mastectomy for cancer allowing estimation of outcomes in relation to margin status/width. The association between pathological margin status and local (LR) and distant recurrence was considered using random effects modelling. PRISMA guidelines were followed. Results Positive margins were associated with increased LR on multivariable analyses (HR, 2·64, (95%CI 2·01–3·46)) and LR was higher regardless of the distance of tumour from the margin defined as positive. After skin-sparing mastectomy, positive margins were associated with increased LR (HR 3·40, (95%CI 1·9–6·2)). In the 4 studies reporting distant recurrence, patients with involved margins had a higher risk (HR 1·53, (95%CI 1·03–2·25)). Conclusions Failure to achieve clear margins after mastectomy may increase the risks of local and distant recurrence. Adequate margin clearance should be recommended to minimize recurrence after mastectomy in National and International Guidelines.

Background/objective Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS). Methods Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS). Results Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6 cm. In non-LMS patients, median age was 58 and median tumor size was 8 cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5 cm and high-grade, n = 49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p = 0.39), D-RFS (53vs63%, p = 0.27), and DSS (67vs91%, p = 0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p = 0.030) and DSS (77vs65%,p = 0.007) in non-LMS patients who received radiation. Conclusions In our cohort, patients with LMS have a low local recurrence rate (12–15%) and modest distant recurrence rate (29–35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.

Background Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and “biological downstaging” in chemoradiation therapy (CRT) for pancreatic cancer (PC). Methods A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. “Biological downstaging” was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). Results The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). Conclusions Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated “biological downstaging” in b-BR in the preoperative CRT strategy.

Treatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS.To compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS.A retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in "functional planned excision" (fPE) group (n = 30) and "functional unplanned excision" (fUPE) group (n = 29) were compared.There was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13).Even though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.

Managing patients with incidental gallbladder cancer requires stratifying patients risk for recurrence and an appreciation for the recurrence patterns characterizing this malignancy. Although standard management includes reresection to remove sites at risk of harboring residual disease and to achieve negative resection margin status, the decision to perform surgery is tempered by an early and frequent distant recurrence, the most common cause of surgical failure. High-risk patients may benefit from neoadjuvant chemotherapy before reresection. The goal of curative-intent reresection is achieving R0 margin status and optimal staging while limiting morbidity and mortality.

Background Colon cancer outcomes are now inferior to rectal cancer outcomes. The sigmoid colon is the most common site of colonic cancer. The aim of this review was to investigate the oncological outcomes for sigmoid cancer. Methods A systematic review and meta-analysis was performed. We included any study of the oncological outcomes for sigmoid cancer such as local recurrence, distant recurrence and disease free survival. A systematic search was conducted in Medline from inception to November 2016. Study quality was evaluated with the Newcastle-Ottawa Scale. The study was registered on PROSPERO (CRD42017069326). Results The search terms returned 1323 results. We identified a total of 17 eligible studies including 5953 patients. The pooled local recurrence rate was 10.5% in 15 studies with 5148 patients (95% CI 0.07–0.14) and heterogeneity measured by I2 was 94%. The pooled distant recurrence rate was 19.5% (7 studies, 2040 patients, 95% CI (0.14–0.25), I2 90%). The pooled disease free survival at 5 years was 80.4% (5 studies, 2336 patients, 95% CI 78.6%–82.1%, I2 11.5%.). The median Newcastle-Ottawa score was 4 out of 9. R1 and R2 resections were excluded or not described in 16/17 studies. Two studies described R1 and R2 rates of 15–20%. Conclusion The pooled local recurrence rate of sigmoid cancer of 10.5% is higher than contemporary rates of local recurrence of rectal cancer. A large number of papers fail to describe or include R1 resections of sigmoid cancer, which are frequently described as palliative.

espanolObjetivo Los sarcomas uterinos son tumores raros con mal pronostico debido a las altas tasas de recurrencia. El papel actual de la 18F-FDG PET/TC en la vigilancia posterior a la terapia aun no esta establecido. Material y metodos Cuarenta y una mujeres con sarcoma uterino se sometieron a 73 estudios 18F-FDG PET/TC para la reestadificacion en la presunta recurrencia o durante el seguimiento en pacientes asintomaticos. Los resultados histopatologicos y/o el seguimiento clinico/de imagenes durante al menos 12 meses se consideraron el estandar de referencia. Se calculo la precision diagnostica y el impacto clinico de la 18F-FDG PET/TC. Resultados treinta y tres estudios 18F-FDG PET/TC fueron positivos, mientras que los 40 estudios restantes fueron negativos. La sensibilidad general, la especificidad, el valor predictivo positivo (VP+), el valor predictivo negativo (VP-) y la precision de la 18F-FDG PET/TC fueron del 88%, 98%, 97%, 91% y 93%. Considerando pacientes con sospecha clinica o radiologica de recidiva (n = 47) y durante el seguimiento (n = 26) la sensibilidad y especificidad, VP+, VP− y precision de 18F-FDG PET/TC fueron del 89%, 100%, 100%, 86% y 94%, y 80%, 95%, 80%, 95% y 92% respectivamente. La 18F-FDG PET/TC tuvo un impacto clinico positivo en 9/73 (12%) estudios y cambio el manejo clinico en 8/41 (20%) pacientes. Conclusion La 18F-FDG PET/TC es un metodo preciso para la deteccion y localizacion de recidivas a distancia en pacientes con sarcoma uterino con buena sensibilidad y especificidad e impacto significativo en la toma de decisiones clinicas. EnglishPurpose Uterine sarcomas are rare tumors with poor prognosis due to the high recurrence rates. The current role of 18F-FDG PET/CT in the post-therapy surveillance is not established yet. Materials and Methods Forty-one women with uterine sarcoma underwent 73 18F-FDG PET/CT for restaging in suspected recurrence or during follow-up in asymptomatic patients. Histopathology results and/or clinical/imaging follow-up for at least 12 months were considered the reference standard. The diagnostic accuracy and clinical impact of 18F-FDG PET/CT was calculated. Results Thirty-three 18F-FDG PET/CT were positive, while the remaining 40 studies were negative. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 18F-FDG PET/CT were 88%, 98%, 97%, 91% and 93%, respectively. Considering patients with clinical or radiological suspicion of recurrence (n = 47) and those during follow-up (n = 26), sensitivity, specificity, PPV, NPV and accuracy of 18F-FDG PET/CT were 89%, 100%, 100%, 86% and 94%, and 80%, 95%, 80%, 95% and 92%, respectively. 18F-FDG PET/CT had a positive clinical impact in 9/73 (12%) studies and changed the clinical management in 8/41 (20%) patients. Conclusions 18F-FDG PET/CT seems to be an accurate method for detection and localization of local and distant recurrence in patients with uterine sarcoma with good sensitivity and specificity and significant impact on clinical decision making.

Highlights • Machine learning models might be a better analytic approach in cervical cancer prognostic prediction than traditional methods. • Our models can provide multitask predictions, which can estimate the individual probability of overall survival, overall recurrence, and site-specific recurrence as well as RFS and OS times at the same time. • A web-based calculator was developed and externally validated to predict prognosis for cervical cancer., Background Machine learning (ML) has been gradually integrated into oncologic research but seldom applied to predict cervical cancer (CC), and no model has been reported to predict survival and site-specific recurrence simultaneously. Thus, we aimed to develop ML models to predict survival and site-specific recurrence in CC and to guide individual surveillance. Methods We retrospectively collected data on CC patients from 2006 to 2017 in four hospitals. The survival or recurrence predictive value of the variables was analyzed using multivariate Cox, principal component, and K-means clustering analyses. The predictive performances of eight ML models were compared with logistic or Cox models. A novel web-based predictive calculator was developed based on the ML algorithms. Results This study included 5112 women for analysis (268 deaths, 343 recurrences): (1) For site-specific recurrence, larger tumor size was associated with local recurrence, while positive lymph nodes were associated with distant recurrence. (2) The ML models exhibited better prognostic predictive performance than traditional models. (3) The ML models were superior to traditional models when multiple variables were used. (4) A novel predictive web-based calculator was developed and externally validated to predict survival and site-specific recurrence. Conclusion ML models might be a better analytic approach in CC prognostic prediction than traditional models as they can predict survival and site-specific recurrence simultaneously, especially when using multiple variables. Moreover, our novel web-based calculator may provide clinicians with useful information and help them make individual postoperative follow-up plans and further treatment strategies.

Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of CRC patients, we find that the increased levels of PV-1, a marker of impaired GVB, is associated with liver bacteria dissemination and metachronous distant metastases. Thus, PV-1 is a prognostic marker for CRC distant recurrence and vascular impairment, leading to liver metastases. Copyright © 2021 Elsevier Inc. All rights reserved.

In developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables.Multinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes.3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08-1.43, p = 0.003). Females70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51-0.94, p 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45-69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78-0.96, p 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years.Age, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.

Background LRR after neoadjuvant chemotherapy (NACT) for BC may impact patient's outcome. This study aimed to evaluate the rates of LRR as first event after NACT and to identify independent predictors of LRR. Methods A total of 10075 women with primary BC and available follow-up from 9 prospective neoadjuvant trials were included in the pooled analysis. The main endpoint was cumulative incidence rates of LRR as first event after NACT; distant recurrence, secondary malignancy or death was defined as competing event. To identify predictors of LRR, surgery type, pathological complete response (pCR=ypT0 ypN0), BC subtypes and other risk factors were evaluated using Fine-Gray's regression model. The two-sided significance level was set to α=0.05. Results After a median follow-up in the entire cohort of 67 months (range 0-215 months), 959 (9.5%) LRRs as first event were observed. Age ( 50 years; p Conclusions Young age, node-positive and G3 tumours as well as non-pCR status and TNBC were found to significantly increase the risk of LRR as first event after NACT. Pts with HR-/HER2+ and TNBC not achieving pCR were at highest risk of LRR. Hence, these BC subtypes might be considered for additional post-neoadjuvant treatment approaches. Legal entity responsible for the study German Breast Group (GBG). Funding Has not received any funding. Disclosure M. Untch: Honoraria (institution), non-financial support: Abbvie; Honoraria (institution), non-financial support: Amgen GmbH; Honoraria (institution), non-financial support: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), non-financial support: Celgene GmbH; Honoraria (institution), non-financial support: Daiji Sankyo; Honoraria (institution), non-financial support: Eisai GmbH; Honoraria (institution), non-financial support: Janssen Cilag; Honoraria (institution), non-financial support: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution): Lilly Deutschland; Honoraria (institution), non-financial support: Sividon Diagnostics; Honoraria (institution), non-financial support: MSD Merck; Honoraria (institution), non-financial support: Mundipharma; Honoraria (institution), non-financial support: Myriad Genetics; Honoraria (institution), non-financial support: Odonate; Honoraria (institution), non-financial support: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), non-financial support: Novartis; Honoraria (institution), non-financial support: Roche Pharma AG; Honoraria (institution), non-financial support: Sanofi Aventis Deutschland GmbH. C. Hanusch: Honoraria (self), Outside the submitted work: Roche; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Celgene; Honoraria (self), Outside the submitted work: Lilly; Honoraria (self), Outside the submitted work: AstraZeneca. P.A. Fasching: Research grant / Funding (institution), The Work Under Consideration for Publication: Novartis; Research grant / Funding (institution), The Work Under Consideration for Publication: Biontech; Honoraria (self), The Work Under Consideration for Publication: Novartis; Honoraria (self), The Work Under Consideration for Publication: Roche; Honoraria (self), The Work Under Consideration for Publication: Pfizer; Honoraria (self), The Work Under Consideration for Publication: Celgene; Honoraria (self), The Work Under Consideration for Publication: Daiichi-Sankyo; Honoraria (self), The Work Under Consideration for Publication: TEVA; Honoraria (self), The Work Under Consideration for Publication: AstraZeneca; Honoraria (self), The Work Under Consideration for Publication: Merck Sharp & Dohme; Honoraria (self), The Work Under Consideration for Publication: Myelo Therapeutics; Honoraria (self), The Work Under Consideration for Publication: Macrogenics; Honoraria (self), The Work Under Consideration for Publication: Eisai; Honoraria (self), The Work Under Consideration for Publication: Puma; Research grant / Funding (institution), The Work Under Consideration for Publication: Cepheid. S. Seiler: Honoraria (self), presentations: Roche; Advisory / Consultancy: Amgen GmbH; Advisory / Consultancy: Hexal; Honoraria (self): Mundipharma; Non-remunerated activity/ies: Novartis. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. H. Tesch: Honoraria (self): Vifor; Honoraria (self): Roche; Honoraria (self): Amgen. C. Jackisch: Honoraria (self), Travel / Accommodation / Expenses: Celgene; Honoraria (self): Roche. A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly. T. Link: Honoraria (self): Amgen; Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Pfizer; Non-remunerated activity/ies: Pharma Mar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self), Non-remunerated activity/ies: Roche. J. Huober: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: MSD Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy: Abbvie. K. Rhiem: Honoraria (self): Tesaro; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca. S. Loibl: Honoraria (institution), Research grant / Funding (institution), The Work Under Consideration for Publication: Roche; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: AbbVie; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Amgen; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: AstraZeneca; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Celgene; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Novartis; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Pfizer; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Seattle Genetics; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Teva; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Vifor; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: PRIME; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Daiichi; Licensing / Royalties, Intellectual Property - Patents & Copyrights: EP14153692.0 pending. All other authors have declared no conflicts of interest.

Oncotype DX (Genomic Health, Redwood City, CA, USA, current list price $4,350.00) is a multigene quantitative reverse transcription-polymerase chain reaction-based assay that estimates the risk of distant recurrence and predicts chemotherapy benefit for patients with estrogen receptor (ER)-positive breast cancers. Studies have suggested that standard histologic variables can provide similar information. Klein and Dabbs et al have shown that Oncotype DX recurrence scores can be estimated by incorporating standard histologic variables into equations (Magee equations). Using a simple modification of the Magee equation, we predict the Oncotype DX recurrence score in an independent set of 283 cases. The Pearson correlation coefficient (r) for the Oncotype DX and average modified Magee recurrence scores was 0.6644 (n=283; P0.0001). 100% of cases with an average modified Magee recurrence score30 (n=8) or an average modified Magee recurrence score9 (with an available Ki-67, n=5) would have been correctly predicted to have a high or low Oncotype DX recurrence score, respectively. 86% (38/44) of cases with an average modified Magee recurrence score≤12, and 89% (34/38) of low grade tumors (NS6) with an ER and PR≥150, and a Ki-6710%, would have been correctly predicted to have a low Oncotype DX recurrence score. Using an algorithmic approach to eliminate high and low risk cases, between 5% and 23% of cases would potentially not have been sent by our institution for Oncotype DX testing, creating a potential cost savings between $56,550.00 and $282,750.00. The modified Magee recurrence score along with histologic criteria may be a cost-effective alternative to the Oncotype DX in risk stratifying certain breast cancer patients. The information needed is already generated by many pathology laboratories during the initial assessment of primary breast cancer, and the equations are free.

Local excision alone is not adapted for cT2T3 rectal cancer, because it is associated with a high local recurrence rate (23% for T2 and 38% for T3) and postoperative therapy after local excision is not efficient to prevent local recurrence. By contrast, neoadjuvant therapy proposes to permit local excision for cT2T3 because the patients are selected by the tumor response. Patients with cT2N0 and small cT3 tumors ≤4 cm are the best indications for this strategy. Local excision permits to select the good pathologic responders ypT0–1 as the optimal candidate for surveillance and to propose radical surgery for the bad responders. Retrospective series of local excision after neoadjuvant therapy for cT2T3 showed 7% local recurrence and 8% distant recurrence. These promising results will be validated after the long-term results of the multicenter trials.

Oncologists have used clinicopathologic features to guide treatment decisions for their breast cancer patients; however, more recently, results of multigene assays are also being considered. A popular assay, Oncotype DX (Genomic Health), stratifies node-negative breast cancer patients into groups that are at low, intermediate, or high risk for distant recurrence and guides decisions about adjuvant chemotherapy utilization.We studied the impact of Oncotype DX recurrence score (ODxRS) compared with that of clinicopathologic features on adjuvant chemotherapy utilization in node-negative breast cancer patients and in node-positive breast cancer patients, and we evaluated whether clinicopathologic features impact the decision for adjuvant chemotherapy utilization in a subset of node-negative breast cancer patients with an intermediate-risk ODxRS.A retrospective study from a single academic institution was performed on 425 patients with invasive breast carcinoma.Adjuvant chemotherapy utilization most significantly correlated with a high-risk ODxRS (P .0001) and, to a lesser degree, patient's age and tumor size. No statistically significant association was found between ODxRS and adjuvant chemotherapy utilization in a subset of patients. In the 156 node-negative breast cancer patients with intermediate-risk ODxRS, high tumor grade most significantly correlated with adjuvant chemotherapy utilization (P .0001).ODxRS, if available, heavily impacts adjuvant chemotherapy utilization and more so than any clinicopathologic factor in node-negative breast cancer patients. Node-negative breast cancer patients in the intermediate-risk group whose tumors were high grade were more likely to receive adjuvant chemotherapy.

Nonrhabdomyosarcoma soft-tissue sarcomas (NRSTS) represent a subgroup of sarcomas that encompass more than 50 distinct histologies. All are rare, but some are more common in patients younger than 20 years of age. The management of patients with many histologies overlap. However, this review will focus on issues unique to a select few NRSTS that are most common in pediatric and adolescent patients. Here, we will discuss the recent advances in the diagnosis, surgical management, and treatment of NRSTS. Adequate surgical local control of the primary tumor is a critical component of the treatment strategy will be emphasized in this review because it determines local and distant recurrence.

Primary cardiac tumors are rare, with an incidence of 0.001%to 0.28% in autopsy series.(1) The third most common primary tumor, although likely under diagnosed, is the cardiac papillary fibroelastoma (CPF).(2) These tumors are benign, do not exhibit local infiltration on histopathologic examination, and carry a low likelihood of recurrence.(3) After excision, recurrence is rare, with a total of4 reported cases of recurrence. Tamin and colleagues2re-ported 3 cases, occurring at 1, 5, and 6 years after initial surgery, that they described as at or near the previous surgical excision site. Kammerer and associates (3) described a case of mitral valve recurrence after 3 years but hypothesized that incomplete resection in attempt to preserve the valve was the likely underlying mechanism. We report a unique case of recurrent CPF after previous resection,occurring at multiple alternate sites throughout the left ventricle (LV).

Background: OncoMasTR is a new multigene prognostic test that was discovered via a novel transcriptional network analysis method that identified upstream Master Transcription Regulators (MTRs), which regulate previously identified prognostic biomarkers. The optimised OncoMasTR signature incorporating clinicopathological information has been shown to be significantly prognostic for predicting distant recurrence in two independent cohorts (TransATAC & a subset of TAILORx from participating Irish centres). The analytical performance characteristics of the OncoMasTR test, comprising solely three prognostic MTRs, were determined. Methods: Relative gene expression levels were measured by RT-qPCR. Assay precision and input ranges were determined using a panel of samples representative of low and high recurrence risk tested across a number of runs incorporating different sources of variation. Serial dilutions of a pooled patient RNA sample was used to establish the linear range and efficiency of the individual gene assays. Results: The overall standard deviation of the OncoMasTR risk score was 0.15, which represents less than 2% of the 10-unit risk score range. The majority of the variability in OncoMasTR results was related to within-run variation (78.2%) with other between-run variation sources contributing relatively little (PCR instrument (0.6%), assay operator (5.2%), reagent lots (7.3%) or loading position (8.7%)). Consistent risk scores were measured for individual samples from 40ng down to 500-fold RNA input range corresponding to CT values of 23 – 36, demonstrating the ability of the test to reliably detect low level expression of the OncoMasTR panel. Importantly, PCR efficiencies were similar for the individual MTR and reference gene assays which ranged from 79 – 95%. Conclusions: The OncoMasTR prognostic test displays robust analytical and clinical performance and is being launched as a CE-marked test. The concise nature of the three gene signature and a simplified workflow that can be readily adopted using standard laboratory equipment will enable convenient qualification by local laboratories for decentralised use. (Less)

Introduction Most adjuvant lung cancer trials only report first sites of failure. The relative timing of local (i.e., local/regional) versus distant recurrence after surgery could potentially affect reported rates of local failure. We assessed this phenomenon in a large group of patients undergoing surgery for early-stage lung cancer. Methods This institutional review board-approved retrospective study identified all patients who underwent surgery at Duke University Medical Center for pathologic stages I to II non-small cell lung cancer between 1995 and 2005. Medical records and pertinent radiographs were reviewed to assess for local and distant sites of recurrence. Both first and subsequent failures were examined. The time interval between surgery and date of local and/or distant failure was compared using the Mann-Whitney U test. Results Of 975 patients undergoing surgery, 250 patients developed recurrent disease (43 local only, 110 distant only, and 97 both). The median time from surgery to local failure was 13.9 months (range, 1–79). The median time to distant failure was 12.5 months (range, 1–79 months). These were not significantly different ( p = 0.34). Among 97 patients who experienced both local and distant failure, 72 (74%) failed at both sites simultaneously, 19 (20%) failed at local sites first, and 6 (6%) failed at distant sites first. Conclusions The time interval from surgery to either local or distant failure is not significantly different. Patterns of failure analyses in which only first sites of failure are scored will underestimate the frequency of local recurrence. Nevertheless, the magnitude of this error is expected to be small.

Introduction The aim of the study was to evaluate the diagnostic precision of serum carcinoembryonic antigen (CEA) in the detection of local or distant recurrence following resectional surgery for colon and rectal cancer. Methods Quantitative meta-analysis was performed on 20 studies, comparing serum CEA with radiological imaging and/or pathology in detecting colorectal cancer (CRC) recurrence in 4285 patients. The cut-off for a ‘positive’ CEA ranged from 3 to 15 ng/ml between the various studies. Sensitivity, specificity and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver operating characteristic curves (SROC) and sub-group analysis were undertaken. Results The overall sensitivity and specificity of CEA for detecting CRC recurrence was 0.64 (95% CI: 0.61–0.67) and 0.90 (95% CI: 0.89–0.91), respectively. The area under the SROC curve was 0.75 (SE = 0.04) and the diagnostic odds ratio was 18.44 (95% CI: 11.94–28.49). A CEA cut-off of 5 ng/ml yielded a higher diagnostic odds ratio than a cut-off of 3 ng/ml (15.5 vs. 11.1). Using meta-regression analysis the optimum CEA cut-off point for the best combination of sensitivity and specificity was 2.2 ng/ml. On sub-group analysis high quality studies, and those involving ≥100 patients yielded a marginal improvement in the sensitivity and specificity with minimal change to the SROC. Conclusion Serum CEA is a test with high specificity but insufficient sensitivity for detecting CRC recurrence in isolation. A cut-off of 2.2 ng/ml may provide an ideal balance of sensitivity and specificity. It may be useful as a first-line surveillance investigation in patients during surgical follow-up based on serial CEA measurements using temporal trends in conjunction with clinical, radiological and/or histological confirmation.

We propose that there is an opportunity to devise new cancer therapies based on the recognition that tumors have properties of ecological systems. Traditionally, localized treatment has targeted the cancer cells directly by removing them (surgery) or killing them (chemotherapy and radiation). These modes of therapy have not always been effective because many tumors recur after these therapies, either because not all of the cells are killed (local recurrence) or because the cancer cells had already escaped the primary tumor environment (distant recurrence). There has been an increasing recognition that the tumor microenvironment contains host noncancer cells in addition to cancer cells, interacting in a dynamic fashion over time. The cancer cells compete and/or cooperate with nontumor cells, and the cancer cells may compete and/or cooperate with each other. It has been demonstrated that these interactions can alter the genotype and phenotype of the host cells as well as the cancer cells. The interaction of these cancer and host cells to remodel the normal host organ microenvironment may best be conceptualized as an evolving ecosystem. In classic terms, an ecosystem describes the physical and biological components of an environment in relation to each other as a unit. Here, we review some properties of tumor microenvironments and ecological systems and indicate similarities between them. We propose that describing tumors as ecological systems defines new opportunities for novel cancer therapies and use the development of prostate cancer metastases as an example. We refer to this as "ecological therapy" for cancer.

The aim of this study was to investigate predictive factors related to distant recurrence (DR) and to determine whether an association exists between locoregional recurrence (LRR) and DR in 956 patients. The multivariate time-dependent Cox regression analysis showed that tumor size (2 cm vsor=2 cm; p0.0001; Hazard Ratio [HR], 3.7; 95% Confidence Interval [CI], 2.2-6.0), pN status (pN(2/3) vs pN(1); p0.0001; HR, 2.3; 95%CI, 1.7-3.1), lymphatic vascular involvement (yes vs no; p=0.001; HR, 1.7; 95%CI, 1.2-2.3) and LRR (yes vs no; p=0.001; HR, dependent on time) were the important prognostic factors for DR. This study confirms a time-dependent association between LRR and DR. A DR occurred immediately after LRR is strongly associated with the LRR, but this association decreases over time, and therefore, a DR occurred lately after LRR is, possibly, not related to this LRR.

The major goals in the treatment of patients with rectal cancer are overall cure, maximizing local control, and maintaining quality of life. Quality of life issues include avoidance of a permanent stoma and maintaining adequate bowel, sexual, and urinary function. Optimizing the surgical technique with a more selective application of adjuvant therapy will meet these goals. This article describes the likely explanations for local and distant recurrence and delineates current clinical trials of adjuvant therapy directed toward minimizing failure despite potentially curative surgical resection.