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The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response. • Patients with BRCA1/2 associated breast cancer should receive olaparib, justifying broader genetic testing. • Genomic testing can identify ER positive, node-positive tumors that do not warrant chemotherapy. • Ovarian suppression may account for much of the chemotherapy benefit in premenopausal women with ER+ breast cancers. • Hypofractionated radiation therapy schedules should be the standard for most postsurgical radiation treatment. • Hereditary gene mutations with differing penetrance should prompt different surveillance and prophylaxis approaches for affected patients. [ABSTRACT FROM AUTHOR]

Background: Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease 2019 (COVID-19) pandemic. Progression of cancers during delay will impact on patients' longterm survival. Patients and methods: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013e2017. We modelled per-patient delay of 3 and 6 months and periods of disruption of 1 and 2 years. Using health care resource costing, we contextualise attributable lives saved and life-years gained (LYGs) from cancer surgery to equivalent volumes of COVID-19 hospitalisations. Results: Per year, 94 912 resections for major cancers result in 80 406 long-term survivors and 1 717 051 LYGs. Perpatient delay of 3/6 months would cause attributable death of 4755/10 760 of these individuals with loss of 92 214/208 275 life-years, respectively. For cancer surgery, average LYGs per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of 3/6 months (an average loss of 0.97/2.19 LYGs per patient), respectively. Taking into account health care resource units (HCRUs), surgery results on average per patient in 2.25 resourceadjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of 3/6 months. For 94 912 hospital COVID-19 admissions, there are 482 022 LYGs requiring 1 052 949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs. Conclusions: Modest delays in surgery for cancer incur significant impact on survival. Delay of 3/6 months in surgery for incident cancers would mitigate 19%/43% of LYGs, respectively, by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59%, respectively, when considering RALYGs. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued. [ABSTRACT FROM AUTHOR]

Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1: 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cNþ) were assigned to cetuximab (n=149) or control (n=151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P=0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P=0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P=0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P=0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. [ABSTRACT FROM AUTHOR]

Surgery represents the only chance of cure for patients with gastroesophageal adenocarcinoma; however, surgery alone does not cure most patients. Over the past decade, several multimodality adjunctive treatments have improved survival for patients with operable gastroesophageal adenocarcinoma who are undergoing surgical resection; these include peri-operative chemotherapy, neoadjuvant chemoradiotherapy, adjuvant chemotherapy and adjuvant chemoradiotherapy. More recently, the results of several large randomised trials are leading to a shift in the peri-operative treatment of gastroesophageal cancer, away from anthracycline-based and towards taxane-based chemotherapy regimens. Emerging data support an increased focus on patients who are at high risk for poor operative outcomes such as R1 resection, and on patients who are at high risk for relapse following surgery such as those with lymph node metastases (N1þ). Future developments may include use of fluorodeoxyglucose-positron emission tomography to inform a switch to non-cross resistant chemotherapy pre-operatively and substitution of alternative treatments for chemotherapy in high risk post-operative node positive patients. Conversely, in molecularly selected subgroups such as microsatellite unstable gastroesophageal cancer, peri-operative or adjuvant chemotherapy may not be helpful, and treatments such as immunotherapy may be considered. In this review, the most upto-date clinical trials and translational research in the field of operable gastroesophageal cancer are discussed; with a focus on how best to risk stratify patients with operable disease for peri-operative treatment plus surgery, and how novel therapies might be integrated into standard treatments in order to improve survival outcomes in this patient group. [ABSTRACT FROM AUTHOR]

Despite optimal surgery and appropriate first-line chemotherapy, ~70%-80% of patients with epithelial ovarian cancer will develop disease relapse. The same modalities as used primarily are available for treatment of recurrent ovarian cancer (ROC). The rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of benefit for selected patients with platinum-sensitive relapse undergoing complete resection. With respect to systemic therapy, tumor histology, BRCA status, the platinum-free interval (PFI) and previous treatment with bevacizumab (anti-VEGF monoclonal antibody) are considered the most important features that influence treatment choice in ROC. In patients with resistant or refractory relapse (PFI<6 months), monotherapy with a non-platinum drug or participation in clinical trials is indicated. The association of non-platinum monotherapy with bevacizumab, followed by maintenance has been approved in this setting in some European countries due to PFS benefit. In patients with partially sensitive relapse (PFI between 6 and 12 months), two options are available: platinum doublets or non-platinum therapy (single agent or combination). The pegylated liposomal doxorubicin/trabectedin combination represents a viable alternative in patients that cannot receive platinum. In platinumsensitive patients, treatment with platinum-based combinations is associated with PFS advantage compared with single agents or non-platinum combinations. The presence of germline or somatic BRCA mutations allows platinum-responsive patients to optimize chemotherapy efficacy and prolonging PFS by the use of olaparib (PARP inhibitor) given as maintenance therapy until progression. In patients not pretreated with bevacizumab in first line, the carboplatin/gemcitabine/bevacizumab combination, followed by maintenance is a viable alternative in platinum-sensitive patients (PFI>6 months). The integration of surgery, with a 'personalized' approach by the use of antiangiogenic agent and of PARP inhibitors is affecting survival of patients with recurrent disease and will help epithelial ovarian cancer to become a chronic disease. [ABSTRACT FROM AUTHOR]

Background: Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers. Materials and methods: Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival. Results: A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8 years (95% CI 4.5-7.2) in region A compared with 14.4 years (95% CI 10.4-18.5) in region B (P<0.01). The effect of surgical strategy remained after adjustment for molecular markers (P=0.001). Conclusion: In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers. [ABSTRACT FROM AUTHOR]

Background: Outcome of pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) is heterogeneous even after adjusting for clinico-pathological prognostic variables. The identification of additional prognostic or even predictive biomarkers is an unmet clinical need. Patients and methods: Forty patients with mucinous appendiceal tumors and PMP were clinically eligible and had evaluable tumor samples obtained after CRS and HIPEC. We carried out next-generations sequencing (NGS) of 50 gene's hotspot regions contained in the Hotspot Cancer Panel v2 using the Ion Torrent Personal Genome Machine platform (Life Technologies). Results: KRAS and GNAS mutations were found in 72% and 52%, and their allelic frequency was below 10% in 55% and 43% of samples, respectively. KRAS and GNAS mutations were associated with worse progression-free survival (PFS) at univariate analysis (P = 0.006 and 0.011, respectively). At multivariate analysis, only KRAS mutations were independently associated with PFS (P = 0.012); GNAS mutations were not--being significantly associated with other poor prognostic features such as incomplete cytoreduction or KRAS mutations. Validation of results was carried out in an independent bi-institutional cohort of 25 patients and the prognostic effect of KRAS mutations was again confirmed in the multivariate model (P = 0.029). NGS approach allowed the discovery of other potentially druggable mutations such as those in PI3K, AKT, LKB1, FGFR3 and PDGFRA. Conclusions: Given the homogeneity of this series and the sensitivity of NGS in this low-cellularity tumor, we demonstrated for the first time a poor prognostic role of KRAS mutations. [ABSTRACT FROM AUTHOR]

Background: Clinical and pathological parameters of patients with epithelial ovarian cancer (EOC) do not thoroughly predict patients' outcome. Despite the good outcome of stage I EOC compared with that of stages III and IV, the risk assessment and treatments are almost the same. However, only 20% of stage I EOC cases relapse and die, meaning that only a proportion of patients need intensive treatment and closer follow-up. Thus, the identification of cell mechanisms that could improve outcome prediction and rationalize therapeutic options is an urgent need in the clinical practice. Patients and methods: We have gathered together 203 patients with stage I EOC diagnosis, from whom snap-frozen tumor biopsies were available at the time of primary surgery before any treatment. Patients, with a median follow-up of 7 years, were stratified into a training set and a validation set. Results and conclusions: Integrated analysis of miRNA and gene expression profiles allowed to identify a prognostic cell pathway, composed of 16 miRNAs and 10 genes, wiring the cell cycle, 'Activins/Inhibins' and 'Hedgehog' signaling pathways. Once validated by an independent technique, all the elements of the circuit resulted associated with overall survival (OS) and progression-free survival (PFS), in both univariate and multivariate models. For each patient, the circuit expressions have been translated into an activation state index (integrated signature classifier, ISC), used to stratify patients into classes of risk. This prediction reaches the 89.7% of sensitivity and 96.6% of specificity for the detection of PFS events. The prognostic value was then confirmed in the external independent validation set in which the PFS events are predicted with 75% sensitivity and 94.7% specificity. Moreover, the ISC shows higher classification performance than conventional clinical classifiers. Thus, the identified circuit enhances the understanding of the molecular mechanisms lagging behind stage I EOC and the ISC improves our capabilities to assess, at the time of diagnosis, the patient risk of relapse. [ABSTRACT FROM AUTHOR]

Background: Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival when compared with limited pulmonary resection. Patients and methods: Data of 522 patients (64.2% men, mean age 64.5 years) who underwent pulmonary resections with curative intent for CRC metastases over a 2-year period were reviewed. All patients were followed for a minimum of 3 years. Disease-specific survival (DSS) and disease-free survival (DFS) were assessed with the Kaplan-Meier method. Factors associated with DSS and DFS were analyzed using a Cox proportional hazards regression model. Results: A total of 394 (75.6%) patients underwent wedge resection, 19 (3.6%) anatomic segmentectomy, 5 (0.9%) lesser resections not described, 100 (19.3%) lobectomy, and 4 (0.8%) pneumonectomy. Accordingly, 104 (19.9%) patients were treated with major anatomic resection and 418 (80.1%) with lesser resection. Operations were carried out with video-assisted thoracoscopic surgery (VATS) in 93 patients. The overall DSS and DFS were 55 and 28.3 months, respectively. Significant differences in DSS and DFS in favor of major resection versus lesser resection (DSS median not reached versus 52.2 months, P = 0.03; DFS median not reached versus 23.9 months, P < 0.001) were found. In the multivariate analysis, major resection appeared to be a protective factor in DSS [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.41-0.96, P = 0.031] and DFS (HR 0.5, 95% CI 0.36-0.75, P < 0.001). The surgical approach (VATS versus open surgical resection) had no effect on outcome. Conclusion: Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results. [ABSTRACT FROM AUTHOR]

Background: Epithelial ovarian cancer continues to have the highest case-fatality ratio of all gynecologic cancers, in spite of ongoing advances in risk-assessment, genomics, tumor biology, cytoreductive surgery, chemotherapy, and molecular-targeted interventions. Primary treatment options for advanced-stage disease not only should reflect current best standards, but also need to be tailored for individual patients, with consideration of local resources. Methods: Formulation of recommendations for optimal primary therapy based on a selective review of data from completed randomized trials, analysis of ongoing trials, and integration with current tumor biology, within the context of individualized clinical care. Recommendations were presented for discussion during an international meeting of experts in ovarian cancer treatment. Results: Key recommendations include full adjuvant therapy for early-stage high-grade serous cancer; tailored utilization of neoadjuvant chemotherapy based on patient comorbidities, extent of disease, and likelihood of achieving optimal surgical cytoreduction; preferred utilization of carboplatin with weekly paclitaxel as primary therapy; consideration of intraperitoneal cisplatin-based therapy in appropriate patients; avoidance of maintenance chemotherapy; lack of necessity for bevacizumab during primary chemotherapy and primary maintenance; acknowledgement of research opportunities and priorities. Conclusions: Integrated multidisciplinary care, including cytoreductive surgery and platinum-based chemotherapy, remain central to the optimal management of women with advanced-stage ovarian cancer. However, even with recent technical advances, the impact on disease-related mortality is limited, and more attention will be focused on the early integration of research, particularly with neoadjuvant chemotherapy and interval cytoreductive surgery. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival, the 5-year survival rates remain ominously low at 45%. Novel therapies are urgently needed. The presence of T cells in the OC tumor microenvironment is correlated with improved progression-free and overall survival, while the presence of regulatory T cells and expression of T-cell inhibitory molecules is correlated with a poor prognosis. These data indicate that immunotherapy could hold promise in improving the treatment of OC. In this review, we will discuss the rational of immunotherapy, highlight current results with cancer vaccines, adoptive T-cell therapy and immunomodulatory agents and summarize the immune effects of selected chemotherapeutic and radiotherapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. Patients and methods: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. Results: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention- to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. [ABSTRACT FROM AUTHOR]

Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates and appears highly promising as a supplement to the tumor-node-metastasis (TNM) classification of various tumors. In colorectal cancer, an international task force has initiated prospective multicenter studies aiming to implement TNM-Immunoscore (TNM-I) in a routine clinical setting. In breast cancer, recommendations for the evaluation of tumor-infiltrating lymphocytes (TILs) have been proposed by an international working group. Regardless of promising results, there are potential obstacles related to implementing TNM-I into the clinic. Diverse methods may be needed for different malignancies and even within each cancer entity. Nevertheless, a uniform approach across malignancies would be advantageous. In nonsmall-cell lung cancer (NSCLC), there are several previous reports indicating an apparent prognostic importance of TILs, but studies on TILs in a TNM-I setting are sparse and no general recommendations are made. However, recently published data is promising, evoking a realistic hope of a clinical useful NSCLC TNM-I. This review will focus on the TNM-I potential in NSCLC and propose strategies for clinical implementation of a TNM-I in resected NSCLC. [ABSTRACT FROM AUTHOR]

Detection of circulating tumor cells (CTC) in squamous cell carcinoma of the head and neck (SCCHN) patients treated with upfront tumor surgery and adjuvant (chemo)radiation was established as independent risk factor for disease-free and overall survival, with distinct prognostic impact depending on tumor site. Detection of CTC might be useful for optimization of adjuvant treatment in SCCHN.Background The prognostic role of persistence of circulating tumor cells (CTC) after upfront tumor surgery for outcome of adjuvant (chemo)radiation in locally advanced squamous cell carcinoma of the head and neck (LASCCHN) was evaluated. Patients and methods In this prospective study, peripheral blood samples from 144 patients with LASCCHN presenting after tumor resection for adjuvant treatment were analyzed for CTC. Their detection was correlated with tumor site, clinical risk factors, disease-free (DFS) and overall survival (OS). Results CTC were detected in 42 of 144 patients (29%). CTC detection was higher in cases with nodal involvement and in carcinomas located at the tonsil or base of tongue but was not influenced by age, smoking history, T stage, extracapsular lymph node extension, surgical margins or the human papillomavirus status. Overall, the presence of CTC was not predictive for OS or DFS. However, while in oropharyngeal carcinomas (OPC, n = 63), the detection of CTC was associated per trend with improved DFS [CTC+ versus CTC− (% of patients without evidence of disease at 2 years): 100% versus 79%; log rank: P = 0.059]; the reverse was observed for carcinomas from other sites (non-OPC, n = 81; CTC+ versus CTC−: 29% versus 75%; P = 0.001). In multivariate analysis, CTC remained an independent prognostic marker for DFS [hazard ratio (HR) 4.3, 95% confidence interval (CI) 1.7–10.9, P = 0.002] and OS (HR 2.7, 95% CI 1.2–6.3, P = 0.016) in non-OPC. Conclusions Assessment of CTC in non-OPC should prove useful for identification of patients who benefit from treatment intensification. The basis for the good prognostic value of CTC in OPC has to be elucidated in future studies. [ABSTRACT FROM AUTHOR]

Gallbladder cancer, although regarded as the most common malignancy of the biliary tract, continues to be associated with a dismal overall survival even in the present day. This review provides an updated, evidence-based model of the pathways of carcinogenesis in gallbladder cancer and its dissemination. The model proposed could serve as the scaffolding for elucidation of the molecular mechanisms involved in gallbladder carcinogenesis.Gallbladder cancer, although regarded as the most common malignancy of the biliary tract, continues to be associated with a dismal overall survival even in the present day. While complete surgical removal of the tumour offers a good chance of cure, only a fraction of the patients are amenable to curative surgery owing to their delayed presentation. Moreover, the current contribution of adjuvant therapies towards prolonging survival is marginal, at best. Thus, understanding the biology of the disease will not only enable a better appreciation of the pathways of progression but also facilitate the development of an accurate genetic model for gallbladder carcinogenesis and dissemination. This review provides an updated, evidence-based model of the pathways of carcinogenesis in gallbladder cancer and its dissemination. The model proposed could serve as the scaffolding for elucidation of the molecular mechanisms involved in gallbladder carcinogenesis. A better understanding of the pathways involved in gallbladder tumorigenesis will serve to identify patients at risk for the cancer (and who thus could be offered prophylactic cholecystectomy) as well as aid oncologists in planning the most suitable treatment for a particular patient, thereby setting us on the vanguard of transforming the current treatment paradigm for gallbladder cancer. [ABSTRACT FROM PUBLISHER]

This systematic review of LDCT screening programs for lung cancer highlights the value of using a cut-off size for nodules warranting further investigation with lower recall rates at prevalent screens and no changes of detection rates, whereas volumetric assessment software at incident screens results in lower recall rates and higher positive predictive values.Background Low-dose computed tomography (LDCT) screening has been shown to reduce mortality from lung cancer but at a substantial cost in diagnostic activity. The objective of this study was to investigate the characteristics of screening programmes associated with recall rates, detection rates and positive predictive values (PPVs). Design We conducted a systematic review of randomised trials and observational studies on LDCT screening for lung cancer. A meta-regression using random-effect logistic regressions was carried out to assess factors influencing recall rates for further investigation, cancer detection rates and PPVs of recall. Results We used data from 63 372 prevalent screens from 16 studies of LDCT screening for lung cancer and 79 302 incident screens from nine studies. In univariable analysis, the use of a cut-off size to define nodules warranting further investigation at prevalent screens reduced recall rates [odds ratio (OR) = 0.44, 95% confidence interval (CI) 0.24–0.82 and OR = 0.42, 95% CI 0.21–0.84 for cut-off sizes of 3–4 and 5–8 mm, respectively], without significant changes in detection rates and PPVs. The number of readers (1 or ≥2) was not associated with changes in recall rates, detection rates and PPVs at prevalent and incident screens. Using the volumetry software at incident screens significantly increased the PPV (OR = 5.02, 95% CI 1.65–15.28) as a result of a decrease in recall rates (OR = 0.25, 95% CI 0.12–0.51), without significant changes in detection rates. Conclusion These results highlight the value of using a cut-off size for nodules warranting further investigation with lower recall rates at prevalent screens, whereas the volumetric assessment software at incident screens results in lower recall rates and higher PPVs. The presence of positron emission tomography in the work-up protocol might be associated with lower rates of surgical procedures for benign findings, although this hypothesis deserves further investigation. [ABSTRACT FROM PUBLISHER]

Background HER2 is overexpressed in 10 to 20% of gastro-esophageal adenocarcinoma (GE-ADK), and is a target for trastuzumab in metastatic patients. We conducted a study to compare HER2 expression between diagnostic biopsies (DBs) and surgical specimens (SSs) of GE-ADK, and to determine the influence of non-trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression. Patients and methods Pathological specimens from biopsies of 228 patients operated on between 2004 and 2011 were collected. Two cohorts treated (n = 141) or not (n = 87) with a NAC were constituted. Two blind independent pathological HER2 analyses on DB and on SS were carried out using immunohistochemistry (IHC) and colorimetric in situ hybridization (CISH). HER-2 overexpression (HER2+) was defined by a score 3+ in IHC, or 2+ with a positive CISH test, according to the specific HER2 scoring guidelines for GE-ADK. Results Paired HER2 status could be determined for 218 out of the 228 patients (95.6%). HER2+ rates were 13.3% on DB (29/218) and 14.7% on SS (32/218). HER2+ tumors were mainly cardial or esophageal adenocarcinomas, with a well-differentiated, intestinal histological type. HER2 status differed between DB and SS in 6% of cases. When DB analyses were added to SS analyses, the relative increase in HER2+ cases was 13.5% (17.1% for patients with NAC and 23.5% for patients with histological response to NAC, versus 7.1% for patients without NAC, P = 0.4, NS). Differences between DB and SS HER2 expression could be explained by intratumoral heterogeneity and by a HER2 expression decrease in SS after NAC in responding patients possibly due to a higher chemosensitivity of HER2-positive clones. Conclusion The determination of HER2 status on DB provides results that complete those obtained with SS. Combining the analysis of DB and of SS enables to optimize the selection of trastuzumab-eligible patients in case of metastatic relapse, and particularly in previously NAC-responding patients. [ABSTRACT FROM PUBLISHER]

Background Based on registries, the European experience has been that <50% of patients are treated according to protocols and/or benefit from the minimum required surgery for ovarian cancer. The French Cancer Plan 2009–2013 considers the definition of qualitative indicators in ovarian cancer surgery in France. This endeavour was undertaken by the French Society of Gynaecologic Oncology (SFOG) in partnership with the French National College of Obstetricians and Gynecologists and all concerned learned societies in a multidisciplinary mindset. Methods The quality indicators for the initial management of patients with ovarian cancer were based on the standards of practice determined from scientific evidence or expert consensus. Results The indicators were divided into structural indicators, including material (equipment), human (number and qualification of staff), and organizational resources, process indicators, and outcome indicators. Conclusions The enforcement of a quality assurance programme in any country would undoubtedly promote improvement in the quality of care for ovarian cancer patients and would result in a dramatic positive impact on their survival. Such a policy is not only beneficial to the patient, but is also profitable for the healthcare system. [ABSTRACT FROM PUBLISHER]

Background The contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete response (pathCR). Methods Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ∼5–6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used. Results One hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months [95% confidence interval (CI), 27.63–NA], with median OS 45.62 months (95% CI 25.56–NA) in Arm A and 43.68 months (95% CI 27.63–NA) in Arm B (P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms. Conclusions These data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial. [ABSTRACT FROM PUBLISHER]

Background In stage IV rectal cancer, palliative surgery is often carried out upfront. This study investigated whether the surgery can be avoided. Patients and methods Forty patients with symptomatic primary rectal adenocarcinoma and synchronous distant metastases deemed to be unresectable received 5 × 5 Gy irradiation and then oxaliplatin-based chemotherapy. Before treatment, 38% of patients had a near-obstructing lesion. The palliative effect was evaluated by questionnaires completed by the patients. Results The median follow-up for living patients was 26 months (range 19–34). The median overall survival was 11.5 months. Eight patients (20%) required surgery during the course of their disease: seven patients required stoma creation and one had local excision. Thirty percent of patients had a complete resolution of pelvic symptoms during the whole course of the disease, and 35% had significant improvement. In the subgroup with a near-obstructing lesion, 23% of patients required stoma creation. In all patients, the probability of requiring palliative surgery at 2 years was 17.5% [95% confidence interval (CI) 13% to 22%), and the probability of sustained good palliative effect after radiotherapy and chemotherapy was 67% (95% CI 58% to 76%). Conclusion Short-course radiotherapy and chemotherapy allowed most patients to avoid surgery, even those with a near-obstructing lesion. ClinicalTrials The trial is registered with ClinicalTrials.gov: number NCT01157806. [ABSTRACT FROM PUBLISHER]

Background Sentinel lymph node (SLN) analysis is conventionally analyzed using immunohistochemistry and in the case of SLN involvement, justifies a second surgery for axillary lymph node (ALN) resection, thus delaying the initiation of adjuvant therapies. Patients and methods Three hundred and eighty-one patients with early stage breast cancer (BC) were considered in this retrospective study. SLNs were detected using combined radioisotope and dye detection. SLN involvement was analyzed using routine intraoperative One-Step Nucleic Acid Amplification (OSNA) assay, in 100 patients and compared with the conventional histopathology carried out previously in 281 patients. Results Considering positive SLNs as ‘++’ (CK19 mRNA copy number>5000), ‘+’ (250 < CK19 mRNA copy number <5000) and positive by inhibition in the OSNA group and macro-, micrometastases and isolated tumor cells in the histopathology group, no difference in SLN involvement rate was found between the two groups with 29.0% and 29.9% of positive SLNs, respectively. Using OSNA intraoperatively, the mean time to process the SLN was 42 min allowing immediate ALN resection, reduced significantly (P < 0.01) the re-intervention rate (9% versus 39%) and significantly (P < 0.01) accelerated the initiation of adjuvant therapy (6.2 versus 8.4 weeks). Conclusions Using OSNA for intraoperative SLN analysis avoids second surgery for ALN resection in most patients and accelerates initiation of adjuvant therapy. [ABSTRACT FROM PUBLISHER]

Background Head and neck soft tissue sarcomas (STS) represent a rare disease. Patients and methods One hundred and sixty-seven patients underwent surgery at our institution with an eradicating intent between 1990 and 2010. Local recurrence (LR), distant metastasis (DM) and disease-specific mortality (DSM) incidence were studied along with clinicopathological prognostic factors. Results Ten-year crude cumulative incidence (CCI) of LR, DM and DSM were 19%, 11% and 26%, respectively (median follow-up 66 months). Independent prognostic factors for DSM were tumor size (P < 0.001) and grade (P = 0.032), while surgical margins obtained a border-line significance (0.070); LR was affected by the tumor size (P = 0.001), while DM only by grade (P = 0.047). The median survival after LR and DM were 14 months and 7 months, respectively. Tumors sited in the paranasal sinus and supraclavicular region had the worst survival. Conclusions Head and neck represent a very critical anatomical site for STS. Achievement of local disease control appears to be crucial, since even LR could be a life-threatening event. [ABSTRACT FROM PUBLISHER]

Background The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine. Patients and methods Since 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome. Results The median age was 29 years (range 5–58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1–22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05). Conclusions Osteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcomas. [ABSTRACT FROM PUBLISHER]

Background To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer. Patients and methods Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m2, day 1) intravenously and capecitabine (1000 mg/m2 twice daily orally, days 1–14) for up to six cycles. Surgery was carried out 6–8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated. Results Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%–90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%–84.5%). Toxic effects were tolerable. No treatment-related deaths occurred. Conclusions Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab–capecitabine–oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer. [ABSTRACT FROM PUBLISHER]

Background Chemoradiation followed by surgery is the preferred treatment of localized gastroesophageal cancer (GEC). Surgery causes considerable life-altering consequences and achievement of clinical complete response (clinCR; defined as postchemoradiation [but presurgery] endoscopic biopsy negative for cancer and positron emission tomographic (PET) scan showing physiologic uptake) is an enticement to avoid/delay surgery. We examined the association between clinCR and pathologic complete response (pathCR). Patients and methods Two hundred eighty-four patients with GEC underwent chemoradiation and esophagectomy. The chi-square test, Fisher exact test, t-test, Kaplan–Meier method, and log-rank test were used. Results Of 284 patients, 218 (77%) achieved clinCR. However, only 67 (31%) of the 218 achieved pathCR. The sensitivity of clinCR for pathCR was 97.1% (67/69), but the specificity was low (29.8%; 64/215). Of the 66 patients who had less than a clinCR, only 2 (3%) had a pathCR. Thus, the rate of pathCR was significantly different in patients with clinCR than in those with less than a clinCR (P < 0.001). Conclusions clinCR is not highly associated with pathCR; the specificity of clinCR for pathCR is too low to be used for clinical decision making on delaying/avoiding surgery. Surgery-eligible GEC patients should be encouraged to undergo surgery following chemoradiation despite achieving a clinCR. [ABSTRACT FROM AUTHOR]

Background Microsatellite instability (MSI) was suggested as a marker for good prognosis in colorectal cancer in 1993 and a systematic review from 2005 and a meta-analysis from 2010 support the initial observation. We here assess the prognostic impact and prevalence of MSI in different stages in a consecutive, population-based series from a single hospital in Oslo, Norway. Patients and methods Of 1274 patients, 952 underwent major resection of which 805 were included in analyses of MSI prevalence and 613 with complete resection in analyses of outcome. Formalin-fixed tumor tissue was used for PCR-based MSI analyses. Results The overall prevalence of MSI was 14%, highest in females (19%) and in proximal colon cancer (29%). Five-year relapse-free survival (5-year RFS) was 67% and 55% (P = 0.030) in patients with MSI and MSS tumors, respectively, with the hazard ratio (HR) equal to 1.60 (P = 0.045) in multivariate analysis. The improved outcome was confined to stage II patients who had 5-year RFS of 74% and 56% respectively (P = 0.010), HR = 2.02 (P = 0.040). Conclusions MSI has an independent positive prognostic impact on stage II colorectal cancer patients after complete resection. [ABSTRACT FROM AUTHOR]