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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.

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 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.

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

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.

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.

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.

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.

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.

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. 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.

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.

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.

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.

Item does not contain fulltext PURPOSE OF REVIEW: The radical surgical approach in the treatment of vulvar cancer patients has led to a favourable prognosis for the majority of patients with early stage vulvar cancer. However, morbidity is impressive, leading to more individualized treatment. The authors have reviewed the most recent literature on the pros and cons of the modifications in treatment, including surgery and primary radiotherapy, for primary squamous cell carcinoma of the vulva and vulvar melanoma. RECENT FINDINGS: The sentinel lymph node procedure is a promising method of staging in patients with early stage squamous cell carcinoma of the vulva and possibly for patients with vulvar melanoma, but its safety still has to be proved. Less radical surgery has led to a higher local and regional recurrence rate. There may be a role for primary radiotherapy of the groin in a selected group of patients. SUMMARY: The authors have concluded that the individualization of treatment for vulvar cancer patients has led to a decrease in morbidity but an increase in recurrences. The increase in recurrences does not appear to compromise prognosis, probably because of the lack of power, based on the low incidence of vulvar cancer. The sentinel lymph node procedure and primary radiotherapy are promising methods to reduce the morbidity of treatment but their safety needs to be studied in randomized trials.

Item does not contain fulltext Vulvar cancer is a rare disease. Squamous-cell carcinomas account for 90% of vulvar cancers. The main mode of spread is lymphogenic to the inguinofemoral lymph nodes. Therefore, elective uni- or bilateral inguinofemoral lymphadenectomy is part of the standard treatment in combination with radical (wide) local excision of the vulvar tumour. Lymph drainage studies in relation to the biological behaviour of vulvar cancer are presented, as well as the anatomy and surgery of the groin. The sentinel lymph node procedure is a relatively new method of staging in vulvar cancer which may lead to the omission of inguinofemoral lymphadenectomy in those patients identified as not having inguinofemoral lymph node metastases. The accuracy of this technique appears to be high, but its safety still has to be proven. Moreover, the role of additional histopathological techniques for the examination of the sentinel lymph nodes needs to be established.

BACKGROUND. The objective of this study was to determine whether modifications in the treatment of patients with vulvar carcinoma influence the rates of recurrence and survival. METHODS. Between 1982 and 1997, 253 patients with T1 and T2 invasive squamous cell carcinoma of the vulva were treated by essentially the same team of gynecologic oncologists, and 168 patients (Group I) underwent radical vulvectomy with en bloc inguinofemoral lymphadenectomy. Standard therapy was changed in 1993, and 85 patients (Group II) underwent wide local excision with inguinofemoral lymphadenectomy through separate incisions. The rates of recurrence and survival were compared between both groups. RESULTS. In Group II, the overall recurrence rate (33.3%) within 4 years was increased compared with Group I (19.9%; P = 0.03). In Group II, 5 of 79 patients (6.3%) developed fatal groin or skin bridge recurrences compared with 2 of 159 patients (1.3%) in Group I (P = 0.029); this did not result in a difference in overall survival. In Group 11, 40 of 79 patients had tumor free margins measuring less than or equal to 8 mm, resulting in 9 local recurrences; whereas 39 of 79 patients had tumor free margins measuring > 8 mm, resulting in no local recurrences (P = 0.002). CONCLUSIONS. The current study showed that fatal recurrences in either the groin or the skin bridge were more frequent after wide local excision and inguinofemoral lymphadenectomy through separate incisions; however, probably due to lack of power, this did not result in shorter survival. In 40 of 79 patients, the histologic margins measured less than or equal to 8 mm, resulting in a high risk of local recurrences. Therefore, the authors recommend obtaining surgical margins of 2 cm for the local treatment of patients with vulvar carcinoma. (C) 2002 American Cancer Society

Age is an important prognostic marker of patient outcome after breast conserving therapy; however, it is not clear how age affects the outcome. This study aimed to explore the relationship between age with the cell quantity and the radiosensitivity of microscopic disease (MSD) in relation to treatment outcome.We employed a treatment simulation framework which contains mathematic models for describing the load and spread of MSD based on a retrospective cohort of breast pathology specimens, a surgery simulation model for estimating the remaining MSD quantity and a tumor control probability model for predicting the risk of local recurrence following radiotherapy.The average MSD cell quantities around the primary tumor in younger (age⩽50years) and older patients were estimated at 1.9∗10(8)cells and 8.4∗10(7)cells, respectively (P0.01). Following surgical simulation, these numbers decreased to 2.0∗10(7)cells and 1.3∗10(7)cells (P0.01). Younger patients had smaller average surgical resection volume (118.9cm(3)) than older patients (162.9cm(3), P0.01) but larger estimated radiosensitivity of MSD cells (0.111Gy(-1) versus 0.071Gy(-1), P0.01).The higher local recurrence rate in younger patients could be explained by larger clonogenic microscopic disease cell quantity, even though the microscopic disease cells were found to be more radiosensitive.

In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patients. This study included a consecutive series of 536 patients a parts per thousand currency sign40 years of age at diagnosis with pathological T1N0-3M0 BC, treated between 1989 and 2005. A multistate survival model was used to evaluate the influences of local treatment and LRR on DMD, adjusted for potential prognostic factors. Patients were treated with mastectomy (N = 213) or BCT (N = 323). Median age at diagnosis was 36.3 years, with a median follow-up of 9.0 years. The 10-year actuarial cumulative incidence of DMD was 30.6 % after mastectomy and 26.3 % after BCT (P = 0.04). In total, 81 (15 %) LRRs were observed. After BCT, patients had a threefold higher risk of LRR than after mastectomy (HR 2.9; 95 % CI 1.6-5.3). Patients with LRR had a higher risk of DMD compared with patients without LRR (HR 5.5; 95 % CI 2.1-14.5). However, BCT was not negatively associated with DMD-after-LRR (HR 0.47; 95 % CI 0.2-1.1, BCT vs mastectomy). In conclusion, although LRR significantly affected DMD, the increased risk of LRR after BCT compared with mastectomy did not lead to a worse DMD outcome in BC patients a parts per thousand currency sign40 years of age.

Endometrial cancer is the most common gynecological malignancy in high-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. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (with ongoing studies of sentinel node biopsy) enables identification of lymph node positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant radiotherapy is used for Stage I-II patients with high-risk factors and Stage III lymph node negative patients. In advanced disease, a combination of surgery to no residual disease and chemotherapy 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:143 pages:37-50 ispartof: location:United States status: published

ObjectiveRadiotherapy is associated with short-term and long-term morbidity. This study compared toxicity rates among patients with endometrial carcinoma (EC) treated with adjuvant external beam radiation therapy (EBRT) on a small pelvic field (SmPF) in comparison with a standard pelvic field (StPF) or an extended field (EF).MethodsPatients with EC preoperatively diagnosed with high-grade histological disease (grade 3 endometrioid, papillary serous, clear cell, and mixed tumor type) or cervical involvement were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy in the University Medical Center Groningen between 1999 and 2008. Patients who received adjuvant EBRT were included in this study. External beam radiation therapy on SmPF (includes only the central pelvis and proximal vagina) was applied in case of negative lymph nodes after adequate lymphadenectomy (≥10 lymph nodes removed at the bilateral obturator and external iliac nodal stations). In case of positive pelvic lymph nodes or inadequate lymphadenectomy, EBRT on StPF was given. External beam radiation therapy on EF was applied in case of common iliac and/or para-aortic lymph node metastases.Retrospectively, using the Common Terminology Criteria for Adverse Events v3.0, acute toxicity was scored during radiotherapy, whereas late toxicity was scored, from 3 months onward after treatment.ResultsToxicity could be evaluated in 75 patients treated with SmPF (n = 33), StPF (n = 28), and EF EBRT (n = 14). Most patients with late adverse events had also reported toxicity during radiotherapy (71%). The most common late adverse events were gastrointestinal tract related, more frequently present in the StPF group (60.7%) compared to SmPF (33.3%; P = 0.032). In particular, nausea and anorexia were more frequent in the StPF group (32.1%) compared to the SmPF group (3.0%; P = 0.004), as well as ileus (14.3% vs 0%, P = 0.039, respectively).ConclusionsTreatment with adjuvant EBRT on SmPF results in less gastrointestinal late adverse events compared to treatment with EBRT on StPF in patients with surgically staged EC.

Patients with pT1cN0 oral squamous cell carcinomas (OSCC) are generally not treated with a neck dissection (ND). However, in 25% of cN0 patients, nodal metastases become apparent during follow-up. Infiltration depth of the primary tumour has been consistently associated with the presence of nodal metastasis, but proposed cut-off depths for performing a ND vary considerably. The aim of this study was to explore the infiltration depth as predictor for the nodal status and to recommend a cut-off depth for performing a ND.From our database of 351 primary oral carcinomas, we selected all pT1-2 tumours (n = 246). Infiltration depth was measured in 212 cases. Neck status was determined by histopathological examination of the dissection specimen, or by at least two years of follow-up.Mean infiltration depth was 5.49 mm (95% CI: 4.86-6.12) in the N0 and 8.40 mm (95% CI: 7.38-9.43) in the N+ group (p Tumour infiltration depth is an independent predictor for nodal status in pT1-2 OSCC. In pT1cN0 tumours, a cut-off at 4.59 mm results in the best predictive value.We recommend an infiltration depth of >= 4 mm as an indication to perform a neck dissection in pT1cN0 OSCC. (C) 2011 Elsevier Ltd. All rights reserved.

Item does not contain fulltext 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. 01 januari 2010

Purpose: To define a method of dose prescription employing Monte Carlo (MC) dose calculation in stereotactic body radiotherapy (SBRT) for lung tumours aiming at a dose as low as possible outside of the PTV.Methods and materials: Six typical T1 lung tumours - three small, three large - were constructed centrally, peripherally in the lung, and nearby the thoracic wall, respectively. For each of these, five treatment plans employing dynamic conformal arc technique were made in which the dose was prescribed to encompass the PTV with the prescription isodose level (PIL) set in a range between 50% and 80% of the isocenter dose. Three shells of respectively 10 mm thickness around the PTV were constructed to assess the dose in the tissues directly adjacent to the PTV.Results: The PTV was nicely covered (mean 98.8% +/- 0.9%) With favourable conformity indices (mean 1.09 +/- 0.1). Mean doses around the PTVs were 73% (+/-1.3%), 76% (+/-3.5%), and 85% (+/-5.1%) of the prescribed dose in shell I for PIL50%, PIL65%, and PIL80%, respectively: 40% (+/-2.6%), 44% (+/-5.1%), 54% (+/-9.3%) in shell 2; and 24% (+/-1.9%), 26% (+/-3.6%), 33% (+/-6.8%) in shell 3. All normal tissue doses including the integral dose were also consistently worst for PIL80%. Monitor units were 30% higher for PIL65%, and 70% higher for PIL50%, compared with PIL80%.Conclusions: To improve normal tissue sparing the dose should be prescribed at an isodose lower than 80% of the isocenter dose in SBRT when using conformal arc technique with MC dose calculation. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 94 (2010) 42-46

Contains fulltext : 50628.pdf (Publisher’s version ) (Closed access) AIM: The radical surgical approach in the treatment of vulvar cancer patients has led to a favorable prognosis for the majority of the patients with early stage squamous cell cancer. However, the morbidity is impressive, leading to more individualized treatment. The aim of this review is to give an overview of the management of vulvar cancer. METHODS: We have reviewed the literature on the modifications in treatment of vulvar cancer with the emphasis on surgery and radiotherapy for primary disease. RESULTS: While surgery is the cornerstone of treatment for early stage squamous cell vulvar cancer (with wide local excision and uni- or bilateral inguinofemoral lymphadenectomy via separate incisions as standard treatment), until now there has been a limited role for primary radiotherapy although this may be an attractive alternative for the inguinofemoral lymphadenectomy in the future. The sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with (99m)technetium-labeled nanocolloid and Patente Blue) is a promising staging technique for patients with vulvar cancer. The clinical implementation of the sentinel lymph node procedure and the role of additional histopathological techniques of the sentinel lymph nodes have to be investigated. In advanced vulvar cancer, chemoradiation followed by surgery should be regarded as the treatment of first choice for these patients. CONCLUSIONS: Due to the rarity of vulvar cancer it is quite clear that further studies will have to be performed by international collaborative groups. The sentinel lymph node procedure and primary radiotherapy are promising methods to reduce morbidity of treatment, but their safety needs to be studied in clinical trials.

A prospective study was undertaken to assess the value of both T2-weighted spin-echo (SE) and contrast-enhanced dynamic gradient-echo (GRE) sequences using MR imaging in differentiating the deep myometrial invasion from lower stages produced by endometrial carcinoma. For the correlation of MR findings with the histopathologic findings, patients who had no myometrial invasion (stage 1 a) and patients in whom tumors were confined to the superficial myometrium (stage 1 b) at pathologic examination were combined as lower stages. Twenty patients with endometrial carcinoma were studied using both techniques. The absence of any detectable tumor (stage 1 a) or the presence of a tumor confined to inner half of myometrium (stage 1 b) and extention of tumor to the outer half of myometrium (stage 1 c) were used as the diagnostic criteria. In pathologic examination of excised specimens, deep myometrial invasion was detected in 9 of 20 patients. The sensitivity, specificity, accuracy, positive predictive values (PPV) and negative predictive values (NPV) of T2-weighted SE in differentiating deep myometrial invasion from combined lower stages were 88, 91, 90, 88, and 91 %, respectively, whereas corresponding values for contrast-enhanced dynamic GRE sequences were 78, 100, 90, 100, and 85 %. Statistical difference between two sequences did not reach a significant level. We conclude that in cases of absence of visible junctional zone with SE sequence, contrast-enhanced dynamic GRE MR imaging may be helpful.

Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P= 4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (>= 4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.