Search

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15-645); in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21-295). The median number of imaging features extracted was 184 (10-6538). The median Radiomics Quality Score was 11% (0-47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15-645); in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21-295). The median number of imaging features extracted was 184 (10-6538). The median Radiomics Quality Score was 11% (0-47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.

The uterine carcinosarcoma (UCS) is a rare entity with poor prognosis. Treatment of FIGO I-II UCS usually consists of surgery with or without adjuvant treatment. Due to the high metastatic potential, aggressive combined modality adjuvant treatment approaches, consisting of chemo- and radiotherapy, have been of interest. Our systematic review aims to compare survival, disease control and toxicity profiles in patients receiving adjuvant chemoradiation to other adjuvant strategies (e.g.observation, chemotherapy or radiotherapy). A total of ten studies were included for a combined cohort size of 6520 patients. Generally, the studies showed a trend towards improved disease control and survival in patients undergoing adjuvant multimodal treatment, although statistical significance was often not reached. Selection bias and non-randomized treatment allocation pose serious challenges to extrapolate these outcomes to clinical practice. We recommend additional prospective research on the role of adjuvant chemoradiation in FIGO I-II UCS.

ObjectiveTo compare the performance of the new ESGO-ESTRO-ESP (European Society of Gynecological Oncology-European Society for Radiotherapy & Oncology-European Society for Pathology) 2020 risk classification system with the previous 2016 risk classification in predicting survival and patterns of recurrence in the Danish endometrial cancer population.MethodsThis Danish national cohort study included 4516 patients with endometrial cancer treated between 2005 and 2012. Five-year Kaplan–Meier adjusted and unadjusted survival estimates and actuarial recurrence rates were calculated for the previous and the new classification systems.ResultsIn the 2020 risk classification system, 81.0% of patients were allocated to low, intermediate, or high-intermediate risk compared with 69.1% in the 2016 risk classification system, mainly due to reclassification of 44.5% of patients previously classified as high risk to either intermediate or especially high-intermediate risk. The survival of the 2020 high-risk group was significantly lower, and the recurrence rate, especially the non-local recurrence rate, was significantly higher than in the 2016 high risk group (2020/2016, overall survival 59%/66%; disease specific 69%/76%; recurrence 40.5%/32.3%, non-local 34.5%/25.8%). Survival and recurrence rates in the other risk groups and the decline in overall and disease-specific survival rates from the low risk to the higher risk groups were similar in patients classified according to the 2016 and 2020 systems.ConclusionThe new ESGO-ESTRO-ESP 2020 risk classification system allocated fewer patients to the high risk group than the previous risk classification system. The main differences were lower overall and disease-specific survival and a higher recurrence rate in the 2020 high risk group. The introduction of the new 2020 risk classification will potentially result in fewer patients at high risk and allocation to the new high risk group will predict lower survival, potentially allowing more specific selection for postoperative adjuvant therapy.

BACKGROUND: The Spanish Customized Adjuvant Therapy (SCAT) trial assessed the role of individualized adjuvant therapy in clinical N0 incidental pN1 and/or N2 non-small cell lung cancer (NSCLC) completely resected. We assessed surgical topics with an in-depth analysis of quality of lymphadenectomy based on International Association for the Study of Lung Cancer (IASLC) recommendations. METHODS: Patients with information about lymphadenectomy available were included (N=451). Prospectively collected data about tumor, type of resection, and postoperative morbidity and quality of lymph node dissection (LND) were retrospectively evaluated. Role of lymph node assessment on survival was analyzed using Kaplan-Meier curves, using regression models to identify prognostic factors. RESULTS: In 33.7%, 17.7% and 49.9% of cases, regions 7, 10 and 11 respectively were not assessed. In 21.1% of patients, less than three lymph node regions were biopsied, while in 19.6% of patients less than six lymph nodes were assessed. In 53,4% of patients only one N1 region was evaluated. From patients with positive N2, 8.9% had no N1 regions biopsied. Twenty-nine percent of patients with at least one N2 lymph node resected shown the highest region involved. Thirty-day postoperative mortality was unknown. Five-year overall survival (OS) was 61.7% (95% CI: 55.4–67.4%), 51.5% (95% CI: 39.2–62.4%) and 42.3% (95% CI: 32.1–52.2%) for patients with N1, N2 and N1+N2 disease, respectively (P

Background and aim There is increased attention for shared decision making (SDM) when deciding on radiotherapy for selected patients with Stage 0–2 breast cancer. This study aimed to explore patients' and health care professionals’ experiences, decisional attributes and needs as input for the development of a patient decision aid to facilitate SDM. Methods Qualitative semi-structured interviews were held with fifteen breast cancer patients, being confronted with a radiotherapy decision one month to eight years earlier. Another fifteen interviews were held with professionals specialized in breast cancer care. Interviews were transcribed verbatim and independently coded by two researchers, who agreed upon relevant issues. Results Most patients made their decision by weighing the advantages of radiotherapy, i.e. comparing the decrease in recurrence risk with and without radiotherapy, and disadvantages, i.e. possible side effects. Patients and professionals agreed that recurrence risks should be communicated, but not on how to deal with uncertainty. There was wide variation in which, and how, side effects were explained by professionals. The most common side effects mentioned by both patients and professionals were skin toxicity, fatigue and breast deformity. Conclusion Patients and professionals appeared to agree on what type of attributes should be communicated during SDM on radiotherapy, but how this should be done is up for discussion. To ensure the patient's voice these attributes and needs need to be incorporated in the risk communication and value elicitation part of the patient decision aid. The format in which the attributes are communicated should be critically evaluated., Highlights • Patients and professionals agree on most important attributes. • These attributes need to be used in a patient decision aid. • There is unwarranted inter doctor variation in informing about side effects. • Professionals differ in opinion how to inform patients about epistemic uncertainties.

Purpose of Review To summarize the current European-based literature and find answers regarding whether there is any specific condition in which robotic adrenalectomy is superior. Recent Findings For the resection of the adrenal glands, laparoscopic adrenalectomy is the gold standard technique worldwide. With the widespread use of robotic technology in surgery, robotic adrenalectomy has become more popular. The safety and feasibility of robotic adrenalectomy has been shown in several studies. However, despite its technical advantages, robotic surgery has not yet shown a significant supremacy over laparoscopic surgery in terms of surgical outcomes. Summary The robotic adrenalectomy is a safe and feasible technique, similar to conventional laparoscopic adrenalectomy. Patients with specific conditions may benefit from robotic surgery. Yet, the high-quality data are still scant.

Endometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Since The Cancer Genome Atlas defined four molecular subgroups of endometrial cancers, the molecular factors are increasingly used to define prognosis and treatment. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (and increasingly sentinel node biopsy) enables identification of lymph node-positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant therapy is used for Stage I-II patients with high-risk factors and Stage III patients; chemotherapy is especially used in non-endometrioid cancers and those in the copy-number high molecular group characterized by TP53 mutation. In advanced disease, a combination of surgery to no residual disease and chemotherapy with or without radiotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease-free interval. ispartof: INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS vol:155 issue:Suppl 1 pages:45-60 ispartof: location:United States status: published

Simple Summary The voltage-gated sodium channel is a type of protein normally expressed in the ‘excitable’ tissues (nerves and muscles) of the body. Epithelial tissues (gut, lungs etc.), which are normally devoid of such a channel, express it at high levels upon becoming cancerous. This occurs also in colorectal cancer cells where the channel subtype is the embryonic (‘neonatal’) variant, nNav1.5. In colorectal cancer cells, as in other solid cancer cells, channel activity promotes invasiveness. However, there is little information on the status of nNav1.5 in human colorectal tissues and how this might relate to patient outcome. Here, we show (i) that nNav1.5 expression is much higher in cancer tissues compared with normal; (ii) that nNav1.5 co-occurs with several other biomarkers of pathological importance; and (iii) that disease-free survival of colorectal patients is inversely correlated with channel expression. In conclusion, nNav1.5 has combined diagnostic and therapeutic potential in clinical management of colorectal cancer. Abstract Voltage-gated Na+ channels (VGSCs) are expressed widely in human carcinomas and play a significant role in promoting cellular invasiveness and metastasis. However, human tissue-based studies and clinical characterization are lacking. In several carcinomas, including colorectal cancer (CRCa), the predominant VGSC is the neonatal splice variant of Nav1.5 (nNav1.5). The present study was designed to determine the expression patterns and clinical relevance of nNav1.5 protein in human CRCa tissues from patients with available clinicopathological history. The immunohistochemistry was made possible by the use of a polyclonal antibody (NESOpAb) specific for nNav1.5. The analysis showed that, compared with normal mucosa, nNav1.5 expression occurred in CRCa samples (i) at levels that were significantly higher and (ii) with a pattern that was more delineated (i.e., apical/basal or mixed). A surprisingly high level of nNav1.5 protein expression also occurred in adenomas, but this was mainly intracellular and diffuse. nNav1.5 showed a statistically significant association with TNM stage, highest expression being associated with TNM IV and metastatic status. Interestingly, nNav1.5 expression co-occurred with other biomarkers associated with metastasis, including hERG1, KCa3.1, VEGF-A, Glut1, and EGFR. Finally, univariate analysis showed that nNav1.5 expression had an impact on progression-free survival. We conclude (i) that nNav1.5 could represent a novel clinical biomarker (‘companion diagnostic’) useful to better stratify CRCa patients and (ii) that since nNav1.5 expression is functional, it could form the basis of anti-metastatic therapies including in combination with standard treatments.

Purpose: Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT. Results: 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus. Conclusions: Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT.

The uterine carcinosarcoma (UCS) is a rare entity with poor prognosis. Treatment of FIGO I-II UCS usually consists of surgery with or without adjuvant treatment. Due to the high metastatic potential, aggressive combined modality adjuvant treatment approaches, consisting of chemo- and radiotherapy, have been of interest. Our systematic review aims to compare survival, disease control and toxicity profiles in patients receiving adjuvant chemoradiation to other adjuvant strategies (e.g.observation, chemotherapy or radiotherapy). A total of ten studies were included for a combined cohort size of 6520 patients. Generally, the studies showed a trend towards improved disease control and survival in patients undergoing adjuvant multimodal treatment, although statistical significance was often not reached. Selection bias and non-randomized treatment allocation pose serious challenges to extrapolate these outcomes to clinical practice. We recommend additional prospective research on the role of adjuvant chemoradiation in FIGO I-II UCS.

Background The Multicenter Selective Lymphadenectomy Trial (MSLT-1) comparing survival after a sentinel lymph node biopsy (SLNB) versus nodal observation in melanoma patients did not show a significant benefit favoring SLNB. However, in subgroup analyses melanoma-specific survival among patients with nodal metastases seemed better. Aim To evaluate the association of performing a SLNB with overall survival in intermediate thickness melanoma patients in a Dutch population-based daily clinical setting. Methods Survival, excess mortality adjusted for age, gender, Breslow-thickness, ulceration, histological subtype, location, co-morbidity and socioeconomic status were calculated in a population of 1,989 patients diagnosed with malignant cutaneous melanoma (1.2–3.5 mm) on the trunk or limb between 2000–2016 in ten hospitals in the South East area, The Netherlands. Results A SLNB was performed in 51% of the patients (n = 1008). Ten-year overall survival after SLNB was 75% (95%CI, 71%-78%) compared to 61% (95%CI 57%-64%) following observation. After adjustment for risk factors, a lower risk on death (HR = 0.80, 95%CI 0.66–0.96) was found after SLNB compared to observation only. Conclusions SLNB in patients with intermediate-thickness melanoma on trunk or limb resulted in a 14% absolute and significant 10-year survival difference compared to those without SLNB.

Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26–5.69), worse overall survival (HR 2.95, 95% CI 1.69–5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11–6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67–10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37–4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.

The Middle East and Africa (MEA) region, a large geographical area, lies at the confluence of Asian, Caucasian and African races and comprises of a population with several distinct ethnicities. The course of management of non-small cell lung cancer (NSCLC) differs as per patients' performance status as well as stage of disease, requiring personalized therapy decisions. Although management of NSCLC has received a significant impetus in the form of molecularly targeted therapies and immune therapies in last few years, surgery remains gold standard for patients with early-stage disease. In case of unresectable disease, radiotherapy and chemotherapy are the primary management modalities. With newer therapies being approved for treatment of early stage disease, use of multi-disciplinary team (MDT) for comprehensive management of NSCLC is of prime importance. A group of experts with interest in thoracic oncology, deliberated and arrived at a consensus statement for the community oncologists treating patients with NSCLC in the MEA region. The deliberation was based on the review of the published evidence including literature and global and local guidelines, subject expertise of the participating panellists and experience in real-life management of patients with NSCLC. We present the proposed regional adaptations of international guidelines and recommends the MDT approach for management of NSCLC in MEA., AstraZeneca FZ LLC, The preparation of this consensus statement and funding of the journal's article processing charges was supported by AstraZeneca FZ LLC. All authors had full access to all the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Non‐small cell lung cancer (NSCLC) accounts for approximately one in five cancer‐related deaths, and management requires increasingly complex decision making by health care professionals. Many centers have therefore adopted a multidisciplinary approach to patient care, using the expertise of various specialists to provide the best evidence‐based, personalized treatment. However, increasingly complex disease staging, as well as expanded biomarker testing and multimodality management algorithms with novel therapeutics, have driven the need for multifaceted, collaborative decision making to optimally guide the overall treatment process. To keep up with the rapidly evolving treatment landscape, national‐level guidelines have been introduced to standardize patient pathways and ensure prompt diagnosis and treatment. Such strategies depend on efficient and effective communication between relevant multidisciplinary team members and have both improved adherence to treatment guidelines and extended patient survival. This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in NSCLC. Implications for Practice This review highlights the value of a multidisciplinary approach to the diagnosis and staging of non‐small cell lung cancer (NSCLC) and makes practical suggestions as to how multidisciplinary teams (MDTs) can be best deployed at individual stages of the disease to improve patient outcomes and effectively manage common adverse events. The authors discuss how a collaborative approach, appropriately leveraging the diverse expertise of NSCLC MDT members (including specialist radiation and medical oncologists, chest physicians, pathologists, pulmonologists, surgeons, and nursing staff) can continue to ensure optimal per‐patient decision making as treatment options become ever more specialized in the era of biomarker‐driven therapeutic strategies., This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in non‐small cell lung cancer.

The purpose of this study was to review the limitations of dose calculation formalisms for photon-emitting brachytherapy sources based on the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) report and to provide recommendations to transition to model-based dose calculation algorithms. Additionally, an overview of these algorithms and approaches is presented. The influence of tissue and seed/applicator heterogeneities on brachytherapy dose distributions for breast, gynecologic, head and neck, rectum, and prostate cancers as well as eye plaques and electronic brachytherapy treatments were investigated by comparing dose calculations based on the TG-43 formalism and model-based dose calculation algorithms. (C) 2019 Elsevier Inc. All rights reserved.

Objective Our aim was to assess the significance of metabolic positron emission tomography (PET) parameters for the prediction of occult mediastinal lymph node metastasis (OLM) and recurrence in patients with clinical-N0 nonsmall cell lung cancer (NSCLC) after surgical resection and lymph node dissection. Materials and methods We evaluated 98 patients with NSCLC [52 adenocarcinoma (ADC), 46 squamous cell carcinoma (SQCC)] who had undergone initial/preoperative fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT). Eligibility criteria for participation were clinically staged as N0 and no FDG uptake in mediastinal lymph nodes on preoperative PET/CT. Clinicopathological characteristics and the diagnosis of recurrence were obtained by reviewing the hospital records. Metabolic parameters [maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis] were determined on F-18-FDG PET/CT images. The association of metabolic parameters with OLM and recurrence was assessed. Results OLM was found in 26 (26.53%) patients. T-stage, central location, and lymphovascular invasion were associated with OLM (respectively, P = 0.007, 0.011

Objective The management of occult lymph node metastasis (LNM) in head and neck squamous cell carcinoma has been a matter of controversy for decades. The vascular density within the tumor microenvironment, as an indicator of ongoing angiogenesis, could constitute an attractive predictor of LNM. The use of the panvascular endothelial antibody CD31 as a marker of occult LNM has never been reported. The aim of this study was to assess the predictive value of CD31 microvascular density for the detection of occult LNM in squamous cell carcinoma of the oral cavity and oropharynx. Study Design Case series with chart review. Setting Tertiary university hospital. Subjects and Methods Intra- and peritumoral microvascular density values were determined in 56 cases of squamous cell carcinoma of the oral cavity (n = 50) and oropharynx (n = 6) with clinically negative necks using the CD31 marker. Statistical associations of CD31 microvascular densities with clinicopathologic data were then established. Results Peritumoral CD31 microvascular density was significantly associated with occult LNM in multivariate analysis (P < .01). Recursive partitioning analysis for this parameter found a cutoff of 19.33, which identified occult LNM with a sensitivity of 91%, a specificity of 65%, a positive predictive value of 40%, a negative predictive value of 97%, and an overall diagnostic accuracy of 71%. Conclusion Peritumoral CD31 microvascular density in primary squamous cell carcinoma of the oral cavity and oropharynx allows accurate prediction of occult LNM.

Stereotactic ablative body radiotherapy (SABR) is popular because of the high rates of local control with low toxicity seen in lung cancer patients. In this study we compared clinically significant toxicity and overall survival for SABR and non-SABR definitive radiotherapy (conformal radiotherapy) patients. A PUBMED search of all human, English language articles on SABR and non-SABR radically treated early stage lung cancer patients was performed until June 2016. Results of these searches were filtered in accordance with a set of eligibility criteria and analyzed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eighty-seven SABR and 25 non-SABR articles were reviewed. There was no significant difference in pneumonitis rates between patients receiving SABR (11.4%; 95% confidence interval [CI], 9.7-13.3) and non-SABR treatment (14.4%; 95% CI, 10.6-18.8; P = .20). Esophagitis was the most common mediastinal toxicity reported with 15% of all non-SABR patients versus 1% of all SABR patients reporting developing Grade >= 2 toxicity. The proportion of patient surviving at 2 and 3 years was superior for SABR patients (P < .001). Treatment-related deaths were rare (approximately 1% for both treatments). Both radiotherapy approaches had low rates of pneumonitis, mediastinal toxicity, and treatment-related deaths. However, significant heterogeneity in the patient population and study regimens limit the power of direct comparison, showing that further high-quality studies are required to define the role of SABR in higher risk and operable patients. Crown Copyright (C) 2017 Published by Elsevier Inc. All rights reserved.

Stereotactic ablative body radiotherapy (SABR) is popular because of the high rates of local control with low toxicity seen in lung cancer patients. In this study we compared clinically significant toxicity and overall survival for SABR and non-SABR definitive radiotherapy (conformal radiotherapy) patients. A PUBMED search of all human, English language articles on SABR and non-SABR radically treated early stage lung cancer patients was performed until June 2016. Results of these searches were filtered in accordance with a set of eligibility criteria and analyzed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eighty-seven SABR and 25 non-SABR articles were reviewed. There was no significant difference in pneumonitis rates between patients receiving SABR (11.4%; 95% confidence interval [CI], 9.7-13.3) and non-SABR treatment (14.4%; 95% CI, 10.6-18.8; P = .20). Esophagitis was the most common mediastinal toxicity reported with 15% of all non-SABR patients versus 1% of all SABR patients reporting developing Grade >= 2 toxicity. The proportion of patient surviving at 2 and 3 years was superior for SABR patients (P < .001). Treatment-related deaths were rare (approximately 1% for both treatments). Both radiotherapy approaches had low rates of pneumonitis, mediastinal toxicity, and treatment-related deaths. However, significant heterogeneity in the patient population and study regimens limit the power of direct comparison, showing that further high-quality studies are required to define the role of SABR in higher risk and operable patients. Crown Copyright (C) 2017 Published by Elsevier Inc. All rights reserved.

Background Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer.Methods PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1: 1) to receive radiotherapy alone (48.6 Gy in 1.8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m(2) given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m (2)) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials. gov, number NCT00411138.Findings 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60.2 months (IQR 48.1-73.1). 5-year overall survival was 81.8% (95% CI 77.5-86.2) with chemoradiotherapy versus 76.7% (72.1-81.6) with radiotherapy (adjusted hazard ratio [HR] 0.76, 95% CI 0.54-1.06; p= 0.11); 5-year failure-free survival was 75 . 5% (95% CI 70.3-79.9) versus 68.6% (63.1-73.4; HR 0.71, 95% CI 0.53-0.95; p= 0.022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (pInterpretation Adjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival.

Background Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. Methods PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1: 1) to receive radiotherapy alone (48.6 Gy in 1.8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m(2) given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m (2)) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials. gov, number NCT00411138. Findings 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60.2 months (IQR 48.1-73.1). 5-year overall survival was 81.8% (95% CI 77.5-86.2) with chemoradiotherapy versus 76.7% (72.1-81.6) with radiotherapy (adjusted hazard ratio [HR] 0.76, 95% CI 0.54-1.06; p= 0.11); 5-year failure-free survival was 75 . 5% (95% CI 70.3-79.9) versus 68.6% (63.1-73.4; HR 0.71, 95% CI 0.53-0.95; p= 0.022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p< 0.0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p< 0.0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity. Interpretation Adjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival.

Purpose Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT. Results 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus. Conclusions Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT.

Although the effectiveness of screening for lung cancer remains controversial, it is a fact that most lung cancers are diagnosed at an advanced stage outside of lung cancer screening programs. In 2013, the U.S. Preventive Services Task Force revised its lung cancer screening recommendation, now supporting lung cancer screening by low-dose computed tomography in patients at high risk This is also endorsed by many major medical societies and advocacy group stake-holders, albeit with different eligibility criteria. In Europe, population-based lung cancer screening has so far not been recommended or implemented, as some important issues remain unresolved. Among them is the open question of how enlarging pulmonary nodules detected in lung cancer screening should be managed. This article comprises two parts: a review of the current lung cancer screening approaches and the potential therapeutic options for enlarging pulmonary nodules, followed by a meeting report including consensus statements of an interdisciplinary expert panel that discussed the potential of the different therapeutic options.

Although the effectiveness of screening for lung cancer remains controversial, it is a fact that most lung cancers are diagnosed at an advanced stage outside of lung cancer screening programs. In 2013, the U.S. Preventive Services Task Force revised its lung cancer screening recommendation, now supporting lung cancer screening by low-dose computed tomography in patients at high risk This is also endorsed by many major medical societies and advocacy group stake-holders, albeit with different eligibility criteria. In Europe, population-based lung cancer screening has so far not been recommended or implemented, as some important issues remain unresolved. Among them is the open question of how enlarging pulmonary nodules detected in lung cancer screening should be managed. This article comprises two parts: a review of the current lung cancer screening approaches and the potential therapeutic options for enlarging pulmonary nodules, followed by a meeting report including consensus statements of an interdisciplinary expert panel that discussed the potential of the different therapeutic options. 2017 International Association for the Study of Lung Cancer. (C) Published by Elsevier Inc. All rights reserved.

Objectives. Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10 years.Methods. Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N = 14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed.Results. Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014.Conclusion. While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients. (C) 2017 Elsevier Inc. All rights reserved.

Introduction: About 5% of ovarian tumours have a non-epithelial histology, including germ cell tumours (GCTs), sex cord-stromal tumours (SCSTs) and sarcomas. Because these non-epithelial ovarian tumours are rare and population-based studies are scarce, the aim of this population-based study is to describe trends in the incidence, treatment and survival of women with these tumours in the Netherlands.Methods: All women diagnosed with non-epithelial ovarian malignant tumours in the Netherlands between 1989 and 2015 were identified from the Netherlands Cancer Registry. Data on demographics, tumour characteristics and initial treatment were collected, and overall survival was analysed.Results: A total of 1258 non-epithelial ovarian tumours were identified comprising 752 GCTs (60%), 341 SCSTs (27%) and 165 sarcomas (13%). The European age-standardised incidence rate (ESR) was 0.4 per 100,000 persons per year for GCTs, 0.2 for SCSTs and 0.1 for sarcomas. Approximately 97% of patients underwent surgical resection for the primary tumour, 31% received systemic treatment and 3% radiotherapy. Between the late 1980s and 2015, five-year overall survival improved for all histologic subtypes: GCTs rose from 73% to 88% (p = 0.03), SCSTs from 64% to 81% (p = 0.57) and sarcomas from 20% to 29% (p = 0.14).Conclusion: Malignant GCTs and SCSTs are rare, and their incidence has not significantly changed over recent decades. They have a good prognosis, which also improved slightly during this period. Primary sarcomas of the ovary are extremely rare and still have a poor prognosis. (C) 2019 Elsevier Ltd. All rights reserved.

Contains fulltext : 171831.pdf (Publisher’s version ) (Open Access) BACKGROUND: About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1:1) to radiotherapy alone (48.6 Gy) in 1.8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure-free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138. FINDINGS: Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for health-related quality of life. Median follow-up was 42.3 months (IQR 25.8-55.1). At completion of radiotherapy and at 6 months, EORTC QLQ-C30 functioning scales were significantly lower (worse functioning) and health-related quality of life symptom scores higher (worse symptoms) for the chemoradiotherapy group compared with radiotherapy alone, improving with time. At 12 and 24 months, global health or quality of life was similar between groups, whereas physical functioning scores remained slightly lower in patients who received chemoradiotherapy compared with patients who received radiotherapy alone. At 24 months, 48 (25%) of 194 patients in the chemoradiotherapy group reported severe tingling or numbness compared with 11 (6%) of 170 patients in the radiotherapy alone group (p

During the last decade, the emerging field of molecular fluorescence imaging has led to the development of tumor-specific fluorescent tracers and an increase in early-phase clinical trials without having consensus on a standard methodology for evaluating an optical tracer. By combining multiple complementary state-of-the-art clinical optical imaging techniques, we propose a novel analytical framework for the clinical translation and evaluation of tumor-targeted fluorescent tracers for molecular fluorescence imaging which can be used for a range of tumor types and with different optical tracers. Here we report the implementation of this analytical framework and demonstrate the tumor-specific targeting of escalating doses of the near-infrared fluorescent tracer bevacizumab-800CW on a macroscopic and microscopic level. We subsequently demonstrate an 88% increase in the intraoperative detection rate of tumor-involved margins in primary breast cancer patients, indicating the clinical feasibility and support of future studies to evaluate the definitive clinical impact of fluorescence-guided surgery.

Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ).Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70).Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved. This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138).

Introduction: Abnormal cervical cytology in patients with endometrial cancer (EC) has been associated with poor outcome. The aim of this study was to evaluate whether cervical cytology could contribute to an improved preoperative identification of high-grade EC (serous, clear cell, carcinosarcoma, high-grade endometrioid EC) in final histology.Methods: A retrospective cohort study was performed in five hospitals in the Netherlands. A total of 554 patients with EC that underwent primary surgical treatment between 2002 and 2010 were included. Primary outcome was defined as the contribution of abnormal cervical cytology in the preoperative identification of high-grade EC. As secondary outcome, recurrence-free survival (RFS) and disease-specific survival were determined based on preoperative cervical cytology, and compared to the currently established risk factors: myometrial invasion, high-grade and lymph vascular space invasion.Results: Abnormal cervical cytology was present in 45.1%. For patients with preoperative inconclusive and high-grade histology, the presence of abnormal cervical cytology contributed to an improved identification of high-grade EC in final histology (odds ratio [OR] 6.40 [95% confidence interval {CI}: 1.92-21.26]; OR 2.86 [95% CI: 1.14-7.14]), respectively. Patients with abnormal cervical cytology had a significant worse 5-year median RFS. Abnormal cervical cytology was independently related to RFS (hazard ratio 1.67 [95% CI: 1.04-2.68]) and disease-specific survival (hazard ratio 3.15 [95% CI: 1.74-5.71]).Conclusions: Abnormal cytology contributes to the preoperative identification of patients with high-grade EC, and is associated with compromised outcome. Future studies are warranted to determine whether cervical cytology could be incorporated into preoperative prediction models for lymph node metastasis.

Medical imaging can visualize characteristics of human cancer noninvasively. Radiomics is an emerging field that translates these medical images into quantitative data to enable phenotypic profiling of tumors. While radiomics has been associated with several clinical endpoints, the complex relationships of radiomics, clinical factors, and tumor biology are largely unknown. To this end, we analyzed two independent cohorts of respectively 262 North American and 89 European patients with lung cancer, and consistently identified previously undescribed associations between radiomic imaging features, molecular pathways, and clinical factors. In particular, we found a relationship between imaging features, immune response, inflammation, and survival, which was further validated by immunohistochemical staining. Moreover, a number of imaging features showed predictive value for specific pathways; for example, intra-tumor heterogeneity features predicted activity of RNA polymerase transcription (AUC = 0.62, p=0.03) and intensity dispersion was predictive of the autodegration pathway of a ubiquitin ligase (AUC = 0.69, p

Merkel cell carcinoma (MCC) is a rare skin cancer that is associated with Merkel cell polyomavirus infection in most cases. Incidence rates of MCC have increased in past decades. Risk factors for MCC include ultraviolet light exposure, immunosuppression and advanced age. MCC is an aggressive malignancy with frequent recurrences and a high mortality rate, although patient outcomes are generally more favourable if the patient is referred for treatment at an early stage. Although advances have been made recently in the MCC field, large gaps remain with regard to definitive biomarkers and prognostic indicators. Although MCC is chemosensitive, responses in advanced stages are mostly of short duration, and the associated clinical benefit on overall survival is unclear. Recent nonrandomised phase 2 clinical trials with antiePD-L1/PD-1 antibodies have demonstrated safety and efficacy; however, there are still no approved treatments for patients with metastatic MCC. Patients with advanced disease are encouraged to participate in clinical trials for treatment, indicating the largely unmet need for durable, safe treatment within this population. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

In the US, whether a sentinel lymph node biopsy (SLNB) is performed depends on tumor and patient factors, including socioeconomic status (SES) and type of health care insurance. We analyzed which patient and tumor characteristics influenced the use of SLNB in a country where every patient has equal access to healthcare.Patients diagnosed with a cutaneous invasive melanoma of a parts per thousand yen1 mm between 2004 and 2011 and living in the northeastern part of the Netherlands were selected from the Netherlands Cancer Registry. Regression analysis was performed to assess the association of patient and tumor characteristics and SLNB use.SLNB was performed in 42 % of the 2,413 included patients. The frequency of performing SLNB increased between 2004 and 2011 from 24 to 55 % (p The use of SLNB has increased significantly between 2004 and 2011. However, in 2011 it was still performed in only 55 % of the Dutch patients with a melanoma a parts per thousand yen1 mm. In patients with head and neck melanoma, older patients, and patients with low SES, SLNB was less frequently performed. Patients with T3 melanomas and a diagnosis made in the university hospital more often had an SLNB performed.

Objective. Lymph node status in early-stage vulvar cancer can be accurately assessed by the sentinel-node (SN) procedure. Molecular techniques, such as DNA-methylation assay, might improve SN assessment. In this study, we selected methylation markers for vulvar cancer and determined if these methylation markers were suitable for lymph node assessment.Methods. We performed methylation specific PCR on DNA isolated from primary tumors, metastatic lymph nodes, and negative lymph nodes from twenty vulvar cancer patients using the following genes: P16INK4a, MGMT, TWIST1, CADM1, TERT, and TFP12. For P16INK4a and MGMT immunohistochemistry was performed on primary tumors and metastatic lymph nodes in order to explore intratumor heterogeneity in gene expression patterns.Results. TERT was methylated in all vulvar cancers, P16INK4a in 13/20, TFP12 in 12/20, CADM1 in 11/20. MGMT in 9/20, and TWIST1 in 7/20. A panel of three methylation markers (P16INK4a, TERT and TFPI2) reached a sensitivity of 67% and specificity of 100% for detection of metastatic lymph nodes. Immunohistochemistry showed intratumor heterogeneity for expression of P16INK4a and MGMT in respectively 55% and 45% of primary tumors.Conclusions. Our study shows methylation for one or more methylation markers in all vulvar cancers. Despite a specificity of 100% our panel of three methylation markers had only moderate sensitivity for metastatic lymph node detection, thereby limiting its applicability for lymph node assessment. Intratumor heterogeneity for expression of P16INK4a and MGMT may reflect intratumor heterogeneity for methylation patterns and thereby in general explain the moderate sensitivity of our marker panel for detection of metastases. (C) 2012 Elsevier Inc. All rights reserved.

Currently, standard treatment for early-stage vulvar cancer typically includes wide local excision of the primary tumor and inguinofemoral lymphadenectomy. The morbidity of this treatment is high. The sentinel lymph node (SLN) procedure provides us with a technique for determining the status of the regional lymph nodes with less treatment-related morbidity. Recently, a large multicenter observational study provided level 3 evidence indicating that it appears safe to omit inguinofemoral lymphadenectomy in case of a negative SLN. This review focuses on the different aspects of the SLN procedure in vulvar cancer.

Purpose To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT). Patients and Methods In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed. Results The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative, close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review (log-rank P = .45 and P = .57, respectively). In multivariate analysis, high-grade invasive ductal carcinoma was associated with an increased risk of local relapse (P = .026; hazard ratio [HR], 1.67), as was age younger than 50 years (P < .0001; HR, 2.38). The boost dose of 16 Gy significantly reduced the local relapse rate (P = .0006; HR, 0.47). For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma, the boost dose reduced the local relapse from 19.4% to 11.4% (P = .0046; HR, 0.51) and from 18.9% to 8.6% (P = .01; HR, 0.42), respectively. Conclusion Young age and high-grade invasive ductal cancer were the most important risk factors for local relapse, while margin status had no significant influence. A boost dose of 16 Gy significantly reduced the negative effects of both young age and high-grade invasive cancer.

To identify actionable elements for improving best practice, this study examined the relative effects of patient, surgeon and hospital factors on surgical treatment variation of 2,929 early breast cancer patients, diagnosed from January 1998 to January 2002 in the region of the Comprehensive Cancer Centre North-Netherlands. Multilevel logistic regression was used to analyze the hierarchically structured data. Apart from the patient level, 43.3% of the treatment variation was due to the hospital and 56.7% to the surgeon, after adjustment for patient characteristics. Although hospital factors like volume, teaching status, and management and policy contributed to this variation, multidisciplinary care seemed the most important actionable hospital factor. Although the surgeon was shown to be an important starting point for quality improvement, actionable elements seemed difficult to identify as factors like surgeon experience and volume were not conclusive and significant variance on this level remained (sigma(2) = 0.149, SE 0.053). We conclude that multidisciplinary care can improve best practice and that further research into actionable surgeon factors is needed.

Background: The value of follow-up surveillance for patients with cutaneous melanoma remains uncertain. In this prospective study the frequency of detection of first melanoma recurrence (FMR) by patient or doctor was analyzed to assist in the future design of evidence-based follow-up guidelines.Methods: Patients who had a recurrence of a previously treated American Joint Committee on Cancer (AJCC) stage I-III primary melanoma (PM) were interviewed to ascertain how their PM and FMR were detected. Factors predicting the detection of PM and FMR were analyzed.Results: The study group comprised 211 patients. In 168 patients, information on detection of their PM was available; 102 PMs (61%) were detected by the patient and 18 (11%) by their partner. Higher AJCC stage, visible location for the patient, and female sex were independent predictive factors for patient-detected PM (P = .03, .002, and .02 respectively). The FMR type was local in 28 (13%), in transit in 35 (17%), in regional lymph nodes in 97 (46%), and distant in 51 (24%). Seventy-three percent of all FMRs were detected by the patient. The presence of a symptom was the only independent predictor of a patient-detected FMR (P Conclusions: Three-quarters of FMRs were detected by patients or their partners, and it should be possible to improve this rate even further by better education. More frequent follow-up visits are thus unlikely to be valuable. Reductions in follow-up frequency may therefore be safe and economically responsible.

The aim of this study was to evaluate prognostic factors for isolated loco-regional recurrence in patients treated for invasive stage I or H breast cancer. The study population comprised 3602 women who had undergone primary surgery for early stage breast cancer, who were enrolled in European Organisation for Research and Treatment of Cancer (EORTC) trials 10801,10854, or 10902, by breast conservation (55%) and mastectomy (45%). The median follow-up time varied from 5.3 (range: 0.6-9.5) to 11.9 years (range: 0.6-17.4). Main outcome was the occurrence of isolated loco-regional recurrence. The results of multivariate analysis showed that younger age and breast conservation were risk factors for isolated loco-regional recurrence (breast cancer under 35 years of age versus over 50 years of age: hazard ratio 2.80 (95% Cl 1.41-5.60)); breast cancer age 35-50 years versus over 50 years: hazard ratio 1.72 (95% CI 1.17-2.54); breast conservation (hazard ratio: 1.82 (95% CI 1.17-2.86)). After perioperative chemotherapy, less isolated loco-regional recurrences were observed (hazard ratio 0.63 (95% Cl 0.44-0.91)). No significant interaction effects were observed. it is concluded that young age and breast conserving therapy are both independent predictors for isolated loco-regional recurrence. As an isolated loco-regional recurrence is a potentially curable condition, women treated with breast conservation or diagnosed with breast cancer at a young age should be monitored closely to detect local recurrence at an early stage. (C) 2005 Elsevier Ltd. All rights reserved.

The aim of this study was to review the literature on currently available non- and minimally-invasive diagnostic methods and analysis of primary tumor characteristics for prediction of inguinofemoral lymph node metastases in patients with primary squamous cell carcinoma of the vulva. We used the English language literature in Pubmed and reference lists from selected articles. Search terms included vulvar carcinoma, prognosis, lymph node metastases, ultrasound, computer tomography, magnetic resonance imaging, positron emission tomography, and sentinel lymph node. No study type restrictions were imposed. Currently no noninvasive imaging techniques exist that are able to predict lymph node metastases with a high enough negative predictive value. A depth of invasion

Background and Objectives. We assessed direct health care costs associated with the most commonly prescribed treatments for indolent follicular non-Hodgkin's lymphoma (FL).Design and Methods. New and previously diagnosed FL patients ( >= 18 years) known during 1997-1998 to 15 Dutch hospitals were selected for inclusion. Each patient was followed for 3 years, and resource use associated with each of the treatments, including watchful waiting, was recorded. The hospital perspective was adopted. Unit costs were based on 2003 price levels.Results, Two hundred patients were included of whom 75% underwent one or more treatments during the 3-year data collection period [25% were not treated because of a watchful waiting strategy (10%) or complete remission (15%)]. Allogeneic and autologous stem cell transplantations were the most expensive treatments, with a mean (median) per patient cost of EURO 45,326 (44,237; n=7) and EURO 18,866 (16,532; n=9), respectively (up to discharge only). Intravenous fludarabine cost EURO 10,651 (9,995; n=33), rituximab (E 10,628; 10,124; n=7), and CHOP E 7,547 (5,833; n=42). Classical FL treatments were found to be the least expensive treatments used with an estimated cost for cylophosphamide, vincristine and prednisone of EURO 5,268 (2,644; n=58), for radiotherapy of EURO 4,218 (4,313; n=52), and for chlorambucil of EURO 2,476 (1,098; n=53).Interpretations and Conclusions. This study presents information on resource use and costs associated with the most commonly prescribed FL treatments. In addition to differences in effectiveness, commonly used treatments vary considerably in terms of resource use and overall cost. This information is of value for resource planning, given the high costs of new treatment modalities.

Aim: In this study, the short-term and tong-term morbidity was assesed after axillary sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (SLNB/ALND) in patients with cutaneous melanoma.Methods: Between 1995 and 2003, 119 axillary SLNBs were performed for cutaneous melanoma. Fifty-eight patients met the inclusion criteria and entered the study.Results: Forty-four patients underwent SLNB alone and 14 patients underwent axillary lymph node dissection after positive SLNB. Complications after SLNB atone: post-operative bleeding (n = 2), seroma (n = 1) and slight lymphedema 11%. Complications after SLNB/ALND: wound infections (n = 2), seroma (n = 5) and slight lymphedema 7%. There were differences between the two groups in short-term complications (p Conclusion: Axillary SLNB atone had a tow complication rate. However, SLNB followed by completion ALND was associated with an increased risk of short- and long-term complications. (c) 2005 Elsevier Ltd. All rights reserved.

Follow-up services for patients with localised cutaneous melanoma are widely discussed but there is no international consensus. Our aim was to discuss frequency and duration of follow-up, type of health professional involved, optimum intensity of routine investigation, and patients' satisfaction with follow-up. Searches of the published work were directed at publications between January, 1985, and February, 2004 on recurrences, subsequent primary melanoma, routine tests, and patients' satisfaction. In a selection of 72 articles, 2142 (6.6%) recurrences were reported, 62% of which were detected by the patients themselves. 2.6% of patients developed a subsequent primary melanoma. Most investigators do not support high-intensity routine follow-up investigations. Of the various follow-up investigations requested by physicians, only medical history and physical examination seem to be cost effective. Lymph-node sonography seems to be a promising method for detection, although survival benefit remains to be proven. Patients were found to be anxious about follow-up visits, although other research showed that provision of information to patients was much appreciated. Published work on the follow-up of patients with cutaneous melanoma has mainly been retrospective and descriptive. Recommendations can be given with only a low grade of evidence. For meaningful guidelines to be developed, prospective, high-quality methodological research is needed.