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Purpose Return to work self-efficacy (RTW-SE) is a strong predictor of return to work (RTW) in employees with mental health problems (MHPs). However, little is known about the development of RTW-SE during the RTW process. In this study, we aimed to identify RTW-SE trajectories in the year following sick leave in employees with MHPs and provided a description of the trajectories in terms of personal and work characteristics, and RTW status. Methods This multi-wave study included 111 employees with MHPs. RTW-SE was measured at baseline, and at 3, 6, and 12 months follow-up with the RTW-SE scale for employees with MHPs. Results Latent class growth analysis revealed six trajectories. In three trajectories employees had increasing RTW-SE scores, namely (class 1) low start, moderate increase, (class 3) moderate start, small increase and (class 5) moderate start, steep increase. The other trajectories were defined by (class 2) persistently high, (class 6) persistently low, and (class 4) decreasing RTW-SE scores over time. Employees across the various trajectories differed significantly with respect to RTW status, and personal and work characteristics measured at baseline, including age, gender, and type of MHP. Less favorable trajectories (class 4 and 6) were characterized by higher age, a higher prevalence of anxiety disorder and lower RTW rates. The most favorable trajectory (class 2) was characterized by a higher proportion of stress-related disorders and less major depression diagnoses. Conclusions Large heterogeneity exists in terms of RTW-SE trajectories in employees with MHPs and significant differences were found across the trajectories regarding personal and work characteristics, and RTW status. Insights into RTW-SE trajectories and their attributes are important to advance more effective and personalized RTW treatment for employees with MHPs.

BACKGROUND AND OBJECTIVE: After whiplash injury, some patients develop chronic whiplash-associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post-injury phases. Therefore, studies were searched that examined temporal changes in pain processing, measured by Quantitative Sensory Testing (QST). DATABASES AND DATA TREATMENT: This systematic review searched three electronic databases (Medline, Web of Science and Embase) for articles meeting the eligibility requirements. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. RESULTS: The 12 included studies presented moderate to good methodological quality. These studies showed altered pain processing within the first month after injury and normalization within 3 months in 59%-78% of the patients. After 3 months, recovery stagnates during the following years. Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non-recovered patients. CONCLUSIONS: Differences in pain processing between recovering and non-recovering patients can be observed already in the acute phase. Early screening for signs of altered pain processing can identify patients with high risk for chronification. These insights in temporal changes show the importance of rehabilitation in the acute phase. Future research should target to develop a standardized (bed-site) QST protocol and collect normative data which could, in relation with self-reported pain parameters, allow clinicians to identify the risk for chronification. SIGNIFICANCE: Altered pain processing is present soon after whiplash injury, but usually recovers within 3 months. Non-recovering patients show little to no improvements in the following years. Differences between recovering and non-recovering patients can be observed by Quantitative Sensory Testing already in the acute phase. Therefore, it is considered a feasible and effective tool that can contribute to the identification of high-risk patients and the prevention of chronification.

Purpose A chordoma is a slow-growing, invasive neoplasm in the neuraxis, thought to arise from notochordal cells. At 10-year follow-up, the average survival rate is 50%, though the interindividual prognosis varies substantially. Here, we aim to provide a comprehensive overview of the genes and proteins expressed in these tumors and their prognostic value, as to facilitate prognostication for chordoma patients. Methods A systematic search of clinical studies that investigated expressed factors related to chordoma survival was performed in PubMed. Data extraction included RNA and protein expression data and prognostic value (in terms of overall survival, progression free survival, disease free survival and recurrence free survival), both by univariate and multivariate analysis. Results Seventy-eight original studies, collectively evaluating 134 expressed factors, were included in this review. By univariate analysis 96, and by multivariate analysis 32 of these molecular factors had a predictive value for patient survival. Of those studied in multivariate analyses, 26 factors had a negative effect while six had a positive effect on patient survival. Conclusions Identification of molecular factors that are associated with survival contributes towards better prognostication of chordoma patients. Given chordoma’s rarity, oftentimes only univariate analyses can be performed. Robust multivariate analyses are scarcer but provide independently significant prognostic factors. The data presented in this review aids in prognostication for the individual patient and facilitates the development of targeted therapies.

Introduction: Neuroendocrine neoplasms (NEN) can originate in different organs, for example, the gastroenteral tract (GE), pancreas (Pan), or lungs (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening. Methods: All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008 to 2018 were selected. Metastatic patterns at initial diagnosis for NEN with different primary origins were compared. In a subcohort of patients from 2 referral hospitals (2014–2019), additional information on, for example, development of metastases after initial presentation was available. Results: In the nationwide cohort, 4,768/11,120 (43%) patients had metastatic disease at diagnosis (GE: 1,504/4,710 [32%]; Pan: 489/1,150 [43%]; and L: 1,230/2,978 [41%]). For GE- and Pan-NEN, the most prevalent metastatic site was the liver (25 and 39%), followed by distant lymph nodes (8 and 8%), whereas only few patients with brain metastases were identified (0% in both). In contrast, for L-NEN, prevalence of metastases in the liver (19%), brain (9%), lung (7%), and bone (14%) was more equal. In the reference network cohort, slightly more NEN patients had metastatic disease (260/539, 48%) and similar metastatic patterns were observed. Conclusion: Almost half of NEN patients were diagnosed with synchronous metastatic disease. L-NEN have a unique metastatic pattern compared to GE- and Pan-NEN. Remarkably, an important part of L-NEN metastases was in the brain, whereas brain metastases were almost absent in GE- and Pan-NEN, indicating utility of screening in L-NEN.

Background Little is known about complications after major duodenopancreatic surgery for duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). Therefore, the incidence and severity of complications after major surgery for MEN1-related dpNETs were assessed. Methods Patients were selected from the population-based Dutch MEN1 database if they had undergone a Whipple procedure or total pancreatectomy from 2003 to 2017. Complications were graded according to the Clavien–Dindo classification (grade III or higher complications were considered a severe complication) and definitions from the International Study Group of Pancreatic Surgery. The Cumulative Complication Index (CCI®) was calculated as the sum of all complications weighted for their severity. Univariable logistic regression was performed to assess potential associations between predictor candidates and a severe complication. Results Twenty-seven patients (median age 43 years) underwent a major duodenopancreatic resection, including 14 Whipple procedures and 13 total pancreatectomies. Morbidity and mortality were 100% (27/27) and 4% (1/27), respectively. A severe complication occurred in 17/27 (63%) patients. The median CCI® was 47.8 [range 8.7–100]. Grade B/C pancreatic fistulas, delayed gastric emptying, bile leakage, hemorrhage, and chyle leakage occurred in 7/14 (50%), 10/27 (37%), 1/27 (4%), 7/27 (26%), 3/27 (11%) patients, respectively. Patients with a severe complication had longer operative time and higher blood loss. After Whipple, new-onset endocrine and exocrine insufficiency occurred in 1/13 and 9/14 patients, respectively. Conclusions Major duodenopancreatic surgery in MEN1 is associated with a very high risk of severe complications and cumulative burden of complications and should therefore be reserved for a select subgroup of patients with MEN1-related dpNETs.

Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1–2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel’s C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78–88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70–0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1–2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com.

Item does not contain fulltext OBJECTIVE: The aim of the study was to obtain an updated overview of regression, persistence, and progression rates of conservatively managed cervical intraepithelial neoplasia grade 1 (CIN 1)/CIN 2/CIN 3. METHODS: Data sources were MEDLINE, Embase, and Cochrane (January 1, 1973-April 14, 2020). Two reviewers extracted data and assessed risk of bias. To estimate outcome rates, we pooled proportions of the individual study results using random-effects meta-analysis, resulting in point estimates and corresponding 95% CIs. Heterogeneity was quantified by the I2 and τ2 measures. RESULTS: Eighty-nine studies were included, 63 studies on CIN 1 (n = 6,080-8,767), 42 on CIN 2 (n = 2,909-3,830), and 7 on CIN 3 (n = 245-351). The overall regression, persistence, and progression to CIN 2 or worse and CIN 3 or worse rates for women with conservatively managed CIN 1 were 60% (95% CI = 55-65, I2 = 92%), 25% (95% CI = 20-30, I2 = 94%), 11% (95% CI = 8-13, I2 = 89%), and 2% (95% CI = 1-3, I2 = 82%), respectively. The overall regression, persistence, and progression rates for CIN 2 were 55% (95% CI = 50-60, I2 = 85%), 23% (95% CI = 19-28, I2 = 83%), and 19% (95% CI = 15-23, I2 = 88%), respectively. Finally, for CIN 3, these were 28% (95% CI = 17-41, I2 = 68%), 67% (95% CI = 36-91, I2 = 84%), and 2% (95% CI = 0-25, I2 = 95%), respectively. Cervical intraepithelial neoplasia grade 2 regression was significantly higher in women 30 years or younger and high-risk human papillomavirus-negative women (66%, 95% CI = 62-70, I2 = 76%; 94%, 95% CI = 84-99, I2 = 60%). Only 2/7,180 (0.03%) and 10/3,037 (0.3%) of the CIN 1 and CIN 2 cases progressed to cervical cancer. CONCLUSIONS: Most CIN 1/CIN 2 will regress spontaneously in less than 24 months, with the highest rates in high-risk human papillomavirus-negative and young women, whereas progression to cancer is less than 0.5%. Conservative management should be considered, especially in fertile women and with expected high compliance. Given the heterogeneity in regression rates of high-grade histology, this should be classified as CIN 2 or CIN 3 to guide management.

PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,542 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided ( https://www.eortc.org/IGCCCG-Update ). CONCLUSION The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

Tumor metastasis is the leading cause of morbidity and mortality in cancer patients [1], [2]. The spine is the third most common site for cancer cells to metastasize after lung and liver, and 30–70% of patients with a tumor have metastatic spinal disease at autopsy [1], [3], [4], [5]. Primary tumors of the breast, prostate, thyroid, lung, gastrointestinal (GI), and kidney are the most common to metastasize to the spine [1], [3], [4], [5]. Within the spinal column, metastases are more commonly found in the thoracic spine, followed by the lumbar spine, while the cervical spine is the least likely location to find metastasis. Spinal bone metastases (SBM) account for over 70% of all osseous metastases and are slightly more common in men than in women. Adults between the ages of 40 and 65 are affected more than any other age group [4], [5], [6]. The prognosis of SBM is abysmal and heavily depends on the primary tumor [7]. Only 10 to 20 percent of the diagnosed patients have survival of more than two years, which implies that caregivers should tailor treatment based on an individual patient profile for an optimal outcome. Graphical tools such as nomograms that can be used to estimate an event’s probability by assigning scores to each important risk factor known to impact the events of interest combined with a prediction model can be used in such a situation. Since nomograms can estimate patient-specific probability of an outcome, they are an excellent decision support system for clinicians and caregivers. Numerous nomograms have been developed for different cancer-specific outcomes [8], [9], [10], [11], [12], [13] and thanks to the technological advancements in the oncological field in the last decade, some of these nomograms have been digitalized [14]. However, until now, no prognostic nomogram has been established for SBM. Therefore, this study aims to develop a nomogram with a user-friendly digital interface that can estimate the 1, 3, and 6-months over-all probabilities of survival for patients with SBM and guide individualized patient management decisions.

PTCL patients exhibit poor survival with existing treatments. We investigated the efficacy of CHOP combined with alemtuzumab in 116 PTCL patients age 61–80 in an open-label, randomized phase 3 trial. Alemtuzumab was given on day 1, to a total of 360 mg in 21 patients, or 120 mg in 37. Hematotoxicity was increased with A-CHOP resulting in more grade ≥3 infections (40% versus 21%) and 4 versus 1 death due to infections, respectively. CR/CRu rate was 60% for A-CHOP and 43% for CHOP, and OR rate was 72% and 66%, respectively. Three-year-EFS, PFS and OS were 27% [15%–39%], 28% [15%–40%], and 37% ([23%–50%] for A-CHOP, and 24% [12%–35%], 29% [17%–41%], and 56% [44%–69%] for CHOP, respectively, showing no significant differences. Multivariate analyses, adjusted for strata and sex confirmed these results (hazard ratio HREFS: 0.7 ([95% CI: 0.5–1.1]; p = 0.094), HRPFS: 0.8 ([95% CI: 0.5–1.2]; p = 0.271), HROS: 1.4 ([95% CI: 0.9–2.4]; p = 0.154). The IPI score was validated, and male sex (HREFS 2.5) and bulky disease (HREFS 2.2) were significant risk factors for EFS, PFS, and OS. Alemtuzumab added to CHOP increased response rates, but did not improve survival due to treatment-related toxicity.

Context Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. Objective This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. Methods A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. Results We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). Conclusion Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.

Purpose We aimed to evaluate quality of life (QoL) using the European Quality of Life Five-Dimensions questionnaire (EQ-5D-3L) in a real-world cohort of Dutch advanced breast cancer (ABC) patients. Secondary, we reported differences in QoL between subgroups of patients based on age, comorbidity, tumor-, and treatment characteristics, and assessed the association of duration of metastatic disease and time to death with QoL. Methods ABC patients who attended the outpatient clinic between October 2010 and May 2011 were asked to fill out the EQ-5D-3L questionnaire. Patient-, disease-, and treatment characteristics were obtained from the medical files. Health-utility scores were calculated. Subgroups were described and compared for utility scores by parametric and non-parametric methods. Results A total of 92 patients were included with a median utility score of 0.691 (Interquartile range [IQR] 0.244). Patients ≥ 65 years had significantly worse median utility scores than younger patients; 0.638 versus 0.743, respectively (p = 0.017). Moreover, scores were significantly worse for patients with versus those without comorbidity (medians 0.620 versus 0.725, p = 0.005). Utility scores did not significantly differ between subgroups of tumor type, type of systemic treatment, number of previous palliative treatment(s), or number or location of metastatic site(s). The remaining survival was correlated with utility scores (correlation coefficient (r) = 0.260, p = 0.0252), especially in the subgroup r = 0.340, p = 0.0169), whereas there was no significant correlation with time since metastatic diagnosis (r = − 0.106, p = 0.3136). Conclusion Within this real-world cross-sectional study, QoL was significantly associated with age, comorbidity, and remaining survival duration. The observation of a lower QoL in ABC patients, possibly indicating the last period of life, may assist clinical decision-making on timing of cessation of systemic antitumor therapy.

Thymic tumors are rare neoplasms showing important clinical and pathologic polymorphisms ranging from low-mitotic encapsulated tumors to a highly aggressive and disseminating one. Complete resection of the tumor with surrounding fatty and mediastinal tissue is of paramount importance and provides good prognosis. Diagnosis of the tumor, radiologic evaluation and implementation of multimodal treatment including preoperative chemotherapy, radiotherapy, postoperative radiotherapy, adjuvant chemotherapy or radiotherapy are important components of the treatment strategy. Some of the stage III tumors can be resected without additional treatment, however, there is a good evidence to support administering preoperative and postoperative chemotherapy and postoperative radiotherapy in these patients providing higher complete resection rate and better survival. For stage IVA thymomas, surgery alone should not be considered as an effective approach and these tumors are considered as unresectable. Chemo/ radiotherapy can be administered to those patients. Of those, postoperative chemotherapy and radiotherapy should be considered if these patients who were deemed to be previously unresectable become resectable. The combined modality treatment should provide prevention of locoregional and intrathoracic recurrence and eventually long-term survival with cure. New targeted therapies including agents against PI3K, CDK, and immune checkpoint PD-1/PD-L1 may lead to higher response rates with less toxicity.

Within a larger national malignant pleural mesothelioma cohort, we identified 43 patients with unusually long survival times. This study aimed to evaluate the diagnostic accuracy in this subgroup, and the diagnosis was confirmed to be correct in most cases. In addition, we searched for clinical factors related to the prolonged survival time. Introduction: Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival. Materials and Methods: Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists. Results: Our study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time. Conclusion: We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors. (C) 2020 Elsevier Inc. All rights reserved.

Indications for autologous (auto-HCT) and allogeneic transplantation (allo-HCT) in relapsed/refractory Hodgkin lymphoma (rrHL) have been long established. The expectation is that long-term outcomes have significantly improved over time with increased experience in these procedures. The objective of this study was to assess whether this is the case and to identify further areas of improvement. A total of 13,639 adult patients receiving an auto-HCT or allo-HCT for rrHL were reported to the European Society for Blood and Marrow Transplantation (EBMT) over a 25-year period. Regarding auto-HCT, recipients are younger, interval between diagnosis and transplant shorter, peripheral blood has become the universal stem cell source and the use of total body irradiation is almost non-existent in recent years. Allo-HCT is currently mostly used as a second transplant; recipients are younger, fitter and less frequently, chemorefractory. Reduced intensity conditioning protocols have vastly replaced myeloablative protocols. Increasing numbers of haplo-HCT have been reported. Both in auto-HCT and allo-HCT, NRM, PFS and OS have significantly improved but relapse remains the main cause of treatment failure. A better selection of patients and improvements in the supportive care has resulted in a reduction in the NRM. Relapse after HCT remains unchanged and further research is needed.

Background: Mucosal melanoma (MM) is rare and has a poor prognosis. Since 2011, new effective treatments are available for advanced melanoma. It is unclear whether patients with mucosal melanoma equally benefit from these new treatments compared with patients with cutaneous melanoma (CM).Methods: Patients with advanced MM and CM diagnosed between 2013 and 2017 were included from a nationwide population-based registry the Dutch Melanoma Treatment Registry. Overall survival (OS) was estimated with the Kaplan-Meier method (also for a propensity score-matched cohort). A Cox model was used to analyse the association of possible prognostic factors with OS.Results: In total, 120 patients with MM and 2960 patients with CM were included. Median OS was 8.7 months and 14.5 months, respectively. Patients with MM were older (median age 70 versus 65 years) and more often female (60% versus 41%), compared with CM. In total, 77% and 2% of the MM patients were treated with first-line immunotherapy and targeted therapy, respectively, compared with 49% and 33% of the CM patients. In contrast to CM, OS for MM did not improve for patients diagnosed in 2015-2017, compared with 2013-2014. ECOG performance score >= 1 (HR = 1.99 [1.26-3.15; p = 0.003]) and elevated LDH level (HR = 1.63 [0.96-2.76]; p = 0.069) in MM were associated with worse survival.Conclusions: Within the era of immune and targeted therapies, prognosis for patients with advanced MM has not improved as much as for CM. Collaboration is necessary to enlarge sample size for research to improve immunotherapeutic strategies and identify targetable mutations. (C) 2020 Elsevier Ltd. All rights reserved.

Objective This study is an evaluation of the overall survival rate and factors affecting survival in patients with osteosarcoma, chondrosarcoma, or Ewing's sarcoma. This study aimed to determine the effect of factors related to the preoperative period, patient, tumor, treatment, and postoperative period on survival. Methods A total of 114 patients (64 male and 50 female) with osteosarcoma, chondrosarcoma, or Ewing's sarcoma treated between 2005 and 2013 were included in this study. All the patients received standard treatment and were followed up regularly. In all, 44 cases of (conventional and telangiectatic) osteosarcoma, 30 cases of Ewing's sarcoma, and 40 cases of high-grade chondrosarcoma were identified using the Bone and Soft Tissue Tumor Registry. Gender, age, tumor size and localization, pathological fractures, histopathological type, grade, surgical treatment, adjuvant treatments, relapse of the disease, and postoperative complication data were obtained from follow-up forms. The learning curve of institutional expertise was also evaluated. The patient survival rate was calculated using the Kaplan-Meier method, and log-rank statistical methods were used to compare survival rates. Results The mean length of survival of the patients was 72 months. There was a 56% 5-year survival rate, and the event-free survival rate was 53%. The survival of patients with Ewing's sarcoma whose prodromal period was less than 12 weeks was significantly higher than that of the other groups (p=0.031). The survival of patients with tumor size greater than 150 cc, with local recurrence and distant metastases was low for all groups. Survival rates were significantly lower in osteosarcoma and Ewing's sarcoma patients with stage III tumor or metastasis at diagnosis. The survival of patients with osteosarcoma diagnosed between 2010 and 2013 was significantly higher than that of the earlier group (p=0.02). Conclusion Decreasing the prodromal period (early diagnosis) can improve survival by preventing the local and systemic spread of the tumor. Increase in the surgical experience is likely to have a positive effect on survival rates, especially for patients with osteosarcoma. The relapse of the disease is a poor prognostic factor for survival despite aggressive surgery and adjuvant therapies. Level of evidence Level IV, Therapeutic study.

Objective Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. Design and methods An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. Results Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. Conclusions Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

The lung is the preferred site of metastasis from soft tissue sarcoma (STS). This systematic review aims to evaluate the outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy (MTS) for the treatment of lung metastases from STS. A systematic review was carried out according to the PRISMA protocol. PubMed, Medline, EMBASE, Cochrane Library, Ovid and Web of Knowledge databases were searched for English-language articles to December 2018 using a predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by two researchers. In total, there were 1306 patients with STS: 1104 underwent MTS and 202 had SBRT. The mean age ranged from 40 to 55.8 years in the MTS group and from 47.9 to 64 years in the SBRT group. The cumulative death rate was 72% (95% confidence interval 59-85%) in the MTS group and 56% (38-74%) in the SBRT group. The cumulative mean overall survival time was 46.7 months (36.4-57.0%) in the MTS group and 47.6 months (33.7-61.5%) in the SBRT group. The cumulative rate of patients alive with disease was 5% (2-9%) in the MTS group and 15% (6-36%) in the SBRT group. Finally, the cumulative rate of patients alive without disease in the two groups was 19% (9-29%) and 20% (10-50%), respectively. Our study showed that local treatment of pulmonary metastases from STS with SBRT, compared with surgery, was associated with a lower cumulative overall death rate and similar overall survival time and survival rates without disease. By contrast, SBRT was associated with a higher survival rate with disease than MTS. Large randomised trials are necessary to confirm these findings and to establish whether SBRT may be a reliable option for early stage disease. (C) 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background: Head and neck sarcomas are rare and difficult to diagnose and manage. Aim: To describe a population of patients with head and neck sarcomas focusing on the effect of symptom duration and time to diagnosis on mortality and recurrence risk. Materials and methods: Fifty-one patients treated in our department between 1998–2013 were retrospectively included. Patient and tumour characteristics as well as dates of interest were obtained from sarcoma registries, charts and pathology records. The effect of symptom duration and time to diagnosis on mortality and risk of recurrence was tested by multivariate analysis. Results: There was a wide range in symptom duration (1–144 months, median 5) and time for diagnosis (0–234 days, median 14) without significant effect on overall mortality, disease-specific mortality or risk of recurrence. Chondrosarcomas in the larynx dominated among the patients with the longest diagnostic duration. Conclusion and significance: The diagnostic process is challenging and in some cases of extremely long duration without effect on mortality. The symptom duration and time to diagnosis in relation to mortality and risk of recurrence has not previously been described. Early biopsy, better imaging and advanced pathological techniques can hopefully speed up the diagnostic process and reduce morbidity and mortality.

Background Quality indicators (QIs) are measurable elements of practice performance and may relate to context, process, outcome and structure. A valid set of QIs have been developed, reflecting the clinical reasoning used in primary care physiotherapy for patients with whiplash-associated disorders (WAD). Donabedian’s model postulates relationships between the constructs of quality of care, acting in a virtuous circle. Aim To explore the relative strengths of the relationships between context, process, and outcome indicators in the assessment of primary care physiotherapy in patients with WAD. Materials and Methods Data on WAD patients (N=810) were collected over a period of 16 years in primary care physiotherapy practices by means of patients records. This routinely collected dataset (RCD-WAD) was classified in context, process, and outcome variables and analyzed retrospectively. Clinically relevant variables were selected based on expert consensus. Associations were expressed, using zero-order, as Spearman rank correlation coefficients (criterion: rs >0.25 [minimum: fair]; α-value = 0.05). Results In round 1, 62 of 85 (72.9%) variables were selected by an expert panel as relevant for clinical reasoning; in round 2, 34 of 62 (54.8%) (context variables 9 of 18 [50.0%]; process variables 18 of 34 [52.9]; outcome variables 8 of 10 [90.0%]) as highly relevant. Associations between the selected context and process variables ranged from 0.27 to 0.53 (p≤0.00), between selected context and outcome variables from 0.26 to 0.55 (p≤0.00), and between selected process and outcome variables from 0.29 to 0.59 (p≤0.00). Moderate associations (rs >0.50; p≤0.00) were found between “pain coping” and “fear avoidance” as process variables, and “pain intensity” and “functioning” as outcome variables. Conclusion The identified associations between selected context, process, and outcome variables were fair to moderate. Ongoing work may clarify some of these associations and provide guidance to physiotherapists on how best to improve the quality of clinical reasoning in terms of relationships between context, process, and outcome in the management of patients with WAD., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/J5N9cYF3BW4

Contains fulltext : 248798.pdf (Publisher’s version ) (Open Access) Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.

Purpose To analyze how the MRI reporting of rectal cancer has evolved (following guideline updates) in The Netherlands. Methods Retrospective analysis of 712 patients (2011–2018) from 8 teaching hospitals in The Netherlands with available original radiological staging reports that were re-evaluated by a dedicated MR expert using updated guideline criteria. Original reports were classified as “free-text,” “semi-structured,” or “template” and completeness of reporting was documented. Patients were categorized as low versus high risk, first based on the original reports (high risk = cT3-4, cN+, and/or cMRF+) and then based on the expert re-evaluations (high risk = cT3cd-4, cN+, MRF+, and/or EMVI+). Evolutions over time were studied by splitting the inclusion period in 3 equal time periods. Results A significant increase in template reporting was observed (from 1.6 to 17.6–29.6%; p Conclusion Updated concepts of risk stratification have increasingly been adopted, accompanied by an increase in template reporting and improved completeness of reporting. Use of updated guideline criteria resulted in considerable downstaging (of mainly high-risk cT-stage and nodal stage). Graphic abstract

Objectives: To analyze clinical features associated to mortality in oncological patients with unplanned admission to the Intensive Care Unit (ICU), and to determine whether such risk factors differ between patients with solid tumors and those with hematological malignancies.Design: An observational study was carried out.Setting: A total of 123 Intensive Care Units across Spain.Patients: All cancer patients with unscheduled admission due to acute illness related to the background oncological disease.Interventions: None.Main variables: Demographic parameters, severity scores and clinical condition were assessed, and mortality was analyzed. Multivariate binary logistic regression analysis was performed.Results: A total of 482 patients were included: solid cancer (n = 311) and hematological malignancy (n = 171). Multivariate regression analysis showed the factors independently associated to ICU mortality to be the APACHE II score (OR 1.102; 95% CI 1.064-1.143), medical admission (OR 3.587; 95% CI 1.327-9.701), lung cancer (OR 2.98; 95% CI 1.48-5.99) and mechanical ventilation after the first 24 h of ICU stay (OR 2.27; 95% CI 1.09-4.73), whereas no need for mechanical ventilation was identified as a protective factor (OR 0.15; 95% CI 0.09-0.28). In solid cancer patients, the APACHE II score, medical admission, antibiotics in the previous 48 h and lung cancer were identified as independent mortality indicators, while no need for mechanical ventilation was identified as a protective factor. In the multivariate analysis, the APACHE II score and mechanical ventilation after 24 h of ICU stay were independently associated to mortality in hematological cancer patients, while no need for mechanical ventilation was identified as aprotective factor. Neutropenia was not identified as an independent mortality predictor in either the total cohort or in the two subgroups.Conclusions: The risk factors associated to mortality did not differ significantly between patients with solid cancers and those with hematological malignancies. Delayed intubation inpatients requiring mechanical ventilation might be associated to ICU mortality. (c) 2021 Elsevier Espana, S.L.U. y SEMICYUC. All rights reserved.

Airway involvement by advanced thyroid carcinoma (TC) constitutes a negative prognosticator, besides being a critical clinical issue since it represents one of the most frequent causes of death in locally advanced disease. It is generally agreed that, for appropriate laryngo-tracheal patterns of invasion, (crico-)tracheal resection and primary anastomosis [(C)TRA] is the preferred surgical technique in this clinical scenario. However, the results of long-term outcomes of (C)TRA are scarce in the literature, due to the rarity of such cases. The relative paucity of data prompts careful review of the available relevant series in order to critically evaluate this surgical technique from the oncologic and functional points of view. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement on the PubMed, Scopus, and Web of Science databases. English-language surgical series published between January 1985 and August 2021, reporting data on ≥5 patients treated for TC infiltrating the airway by (C)TRA were included. Oncologic outcomes, mortality, complications, and tracheotomy-dependency rates were assessed. Pooled proportion estimates were elaborated for each end-point. Thirty-seven studies were included, encompassing a total of 656 patients. Pooled risk of perioperative mortality was 2.0%. Surgical complications were reported in 27.0% of patients, with uni- or bilateral recurrent laryngeal nerve palsy being the most common. When dealing with purely (C)TRA-related complications (i.e., excluding those due to the thyroidectomy), the incidence was 21.2%, and anastomotic dehiscence/leak was the most frequent. Permanent tracheotomy was required in 4.0% of patients. Oncologic outcomes varied among different series with 5- and 10-year overall survival rates ranging from 61% to 100% and 42.1% to 78.1%, respectively. Five- and 10-year disease specific survival rates ranged from 75.8% to 90% and 54.5% to 62.9%, respectively. Therefore, locally advanced TC with airway invasion treated with (C)TRA provides acceptable oncologic outcomes associated with a low permanent tracheotomy rate. The reported incidence of complications, however, indicates the need for judicious patient selection, meticulous surgical technique, and careful postoperative management.

Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related factors associated with the development of distant metastasis (DM) and with overall survival (OS) after DM diagnosis in patients with malignant peripheral nerve sheath tumors (MPNST). Methods: All patients diagnosed with primary MPNST from 1988 to 2019 who were surgically treated for the primary tumor were included. Multivariable Cox regression analyses were performed to identify factors associated with DM and OS after DM diagnosis. Results: A total of 383 patients were included in this analysis, of which 150 developed metastatic disease. No differences in clinicopathologic characteristics and clinical outcome were found between patients with synchronous and metachronous DM. Neurofibromatosis type 1 (NF1), high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. NF1 and more than two metastasis sites were independently associated with worse OS after DM diagnosis. Metastasectomy, chemotherapy and the metastatic site category ‘other’ were associated with prolonged survival after DM diagnosis. Conclusions: This analysis provides important insights into clinicopathologic and treatment factors associated with outcomes in metastatic MPNST. Moreover, NF1-status is associated with a higher risk of DM, it is also independently associated with worse survival in metastatic MPNST.

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease

Contains fulltext : 239059.pdf (Publisher’s version ) (Closed access) BACKGROUND AND OBJECTIVES: Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC. METHODS: From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first-line FOLFIRINOX (April 2015-December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated. RESULTS: A total of 252 patients were included, with a median OS of 14 months. Thirty-two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index ≤1, and CA 19.9 1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein ≥ 270° were independent factors decreasing the probability of resection (c-index: 0.79). CONCLUSIONS: Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision-making process and counseling of these patients.

Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study.

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach, The authors would like to thank Peter E. Clark from Atrium Health, Levine Cancer Institute, Charlotte, NC, USA, for his contribution to the Delphi survey. Angela Corstorphine of Kstorfin Medical Communications Ltd provided medical writing support with the preparation of this manuscript; this support was funded jointly by EAU and ESMO.

Introduction Parathyroid carcinoma represents a rare cause of primary hyperparathyroidism. Distinguishing carcinoma from the benign tumors underlying primary hyperparathyroidism remains challenging. The diagnostic criteria for parathyroid carcinoma are local and/or metastatic spreading. Atypical parathyroid adenomas share other histological features with carcinomas but lack invasive growth. Somatostatin receptors are commonly expressed in different neuroendocrine tumors, but whether this also holds for parathyroid tumors remains unknown. Aim Our aim is to examine the immunohistochemical expression of somatostatin receptor 1–5 in parathyroid typical adenomas, atypical adenomas and carcinomas. Methods We used a tissue microarray construct from a nationwide cohort of parathyroid carcinomas (n = 32), age- and gender-matched typical parathyroid adenomas (n = 72) and atypical parathyroid adenomas (n = 27) for immunohistochemistry of somatostatin receptor subtypes 1–5. We separately assessed cytoplasmic, membrane and nuclear expression and also investigated the associations with histological, biochemical and clinical characteristics. Results All parathyroid tumor subgroups expressed somatostatin receptors, although membrane expression appeared negligible. Except for somatostatin receptor 1, expression patterns differed between the three tumor types. Adenomas exhibited the weakest and carcinomas the strongest expression of somatostatin receptor 2, 3, 4 and 5. We observed the largest difference for cytoplasmic somatostatin receptor 5 expression. Conclusions Parathyroid adenomas, atypical adenomas and carcinomas all express somatostatin receptor subtypes 1–5. Somatostatin receptor 5 may serve as a potential tumor marker for malignancy. Studies exploring the role of somatostatin receptor imaging and receptor-specific therapies in patients with parathyroid carcinomas are needed.

Aims: Chondrosarcoma, osteosarcoma and Ewing sarcoma form the majority of malignant primary tumours of bone. High-grade bone sarcomas require intensive treatment due to their rapid and invasive growth pattern and metastasising capabilities. This nationwide study covers overall incidence, treatment and survival patterns of bone sarcomas in a 15-year period (2000-2014) in the total population of the Netherlands.Patients and methods: Data for this study were derived from the Netherlands Cancer Registry, which receives primary notification from the national pathology database. Classification and categorisation was based on the ICD-O-3 classification and the WHO classification 2013 applied according to our clinicopathological expertise. Overall incidence over the 15-year-period was calculated as a rate per 100,000 person-years (using the European Standardised Rate, ESR). Survival was analysed with Kaplan-Meier curves and Cox proportional hazards regression.Results: Incidence for high-grade chondrosarcoma (n = 429) was estimated at 0.15 per 100,000 ESR, and 5-year overall survival at 65.9% (95% confidence interval (CI): 61.0%-70.4%). Incidence for high-grade central osteosarcoma (n = 605) was estimated at 0.25 per 100,000 ESR and 5-year survival at 53.9% (95% CI: 49.7%-58.0%). Ewing sarcoma incidence (n = 334) was estimated at 0.15 per 100,000 ESR and 5-year survival at 59.3% (95% CI: 53.5%-64.6%). For high-grade central osteosarcoma, treatment at a bone tumour centre was associated with better survival (HR 0.593).Conclusions: This study provides comprehensive incidence estimates for all the main primary bone sarcomas over a 15-year time period in a Northern European country with little migration. Centralisation of bone sarcoma care improves the clinical outcome in osteosarcoma.

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p

Objectives. This study aims to assess the impact of surgical margin and malignancy grade on overall survival (OS) and local recurrence free rate (LRFR) for soft tissue sarcomas (STS) of the thoracic wall. Methods. This retrospective cohort study identified 88 patients, diagnosed and treated surgically for a nonmetastatic STS located in the thoracic wall between 1995 and 2013, using the population based and validated Aarhus Sarcoma Registry and Danish Sarcoma Registry. The Kaplan-Meier method was used to estimate OS and LRFR. Multivariate Cox analyses were used to determine prognostic factors for OS and LRFR. Results. The 5-year OS was 55% (95% confidence interval (CI): 0.44-0.65) and 5-year LRFR was 77% (95% CI: 0.67-0.85). High malignancy grade and intralesional/marginal resection were identified as negative predictors for OS. High grade was the only prognostic factor associated with a lower LRFR. Conclusions. In this large, single institution, study tumor grade was the key predictor for OS and LRFR. Surgical margin only statistically significantly influenced mortality, not local recurrence.

Introduction: Serum carcinoembryonic (CEA) antigen is used as a diagnostic screening tool during follow-up in colorectal cancer patients. However, it remains unclear whether preoperative serum CEA is a reliable marker in the follow-up to predict recurrence. The aim of the study is to determine the value of elevated pre- and postoperative serum carcinoembryonic antigen levels (CEA > 5 µg/L) as an independent prognostic factor for locoregional and distant recurrence in patients who underwent curative surgery for colorectal cancer. Methods: This single center retrospective observational cohort study includes patients who underwent curative surgery for colorectal cancer between 2005 and 2015 and had pre- and postoperative serum CEA measurements. Five-year disease-free survival and multivariate Cox regression analyses were performed to adjust for confounding factors. Results: Preoperative serum CEA level was measured in 2093 patients with colorectal cancer. No significant association was found between an elevated preoperative serum CEA and locoregional recurrence (adjusted hazard ratio (HR) 1.29 (95% confidence interval (CI) 0.91, 1.84; P=0.26)). However, a significant association was found between an elevated preoperative serum CEA and systemic recurrence (adjusted HR 1.58 (95% CI 1.25, 2.00; PConclusions: The preoperative serum CEA level is an independent prognostic factor for systemic metastasis after curative surgery for colorectal cancer in patients with stage I–III disease. The level is the most sensitive for hepatic metastasis compared to metastasis to other anatomic sites.

Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa., SCOPUS: ar.j, info:eu-repo/semantics/published

Background and Purpose: During the months and years post-stroke, treatment benefits from endovascular therapy (EVT) may be magnified by disability-related differences in morbidity/mortality or may be eroded by recurrent strokes and non-stroke-related disability/mortality. Understanding the extent to which EVT benefits may be sustained at 5 years, and the factors influencing this outcome, may help us better promote the sustenance of EVT benefits until 5 years post-stroke and beyond.Methods: In this review, undertaken 5 years after EVT became the standard of care, we searched PubMed and EMBASE to examine the current state of the literature on 5-year post-stroke outcomes, with particular attention to modifiable factors that influence outcomes between 3 months and 5 years post-EVT.Results: Prospective cohorts and follow-up data from EVT trials indicate that 3-month EVT benefits will likely translate into lower 5-year disability, mortality, institutionalization, and care costs and higher quality of life. However, these group-level data by no means guarantee maintenance of 3-month benefits for individual patients. We identify factors and associated “action items” for stroke teams/systems at three specific levels (medical care, individual psychosocioeconomic, and larger societal/environmental levels) that influence the long-term EVT outcome of a patient. Medical action items include optimizing stroke rehabilitation, clinical follow-up, secondary stroke prevention, infection prevention/control, and post-stroke depression care. Psychosocioeconomic aspects include addressing access to primary care, specialist clinics, and rehabilitation; affordability of healthy lifestyle choices and preventative therapies; and optimization of family/social support and return-to-work options. High-level societal efforts include improving accessibility of public/private spaces and transportation, empowering/engaging persons with disability in society, and investing in treatments/technologies to mitigate consequences of post-stroke disability.Conclusions: In the longtime horizon from 3 months to 5 years, several factors in the medical and societal spheres could negate EVT benefits. However, many factors can be leveraged to preserve or magnify treatment benefits, with opportunities to share responsibility with widening circles of care around the patient.

Simple Summary: Penile cancer is a rare but aggressive malignancy characterized by rapid tumor growth as well as prompt metastasis in groin lymphatics. While localized diseases can be successfully cured by surgery in most cases, no truly effective treatment options have been established for metastatic diseases as of yet. In the current investigation, we assessed the value of selected members of the PI3K/mTOR/AKT pathway to serve as tumor markers or therapeutic targets for this disease. Higher expression of AKT was significantly more prevalent in high-grade tumors and independently predictive of the worse survival parameters, while increased expression of pmTOR was associated with an inferior prognosis as well. Treatment with the pan-AKT inhibitor capivasertib in PeCa cell lines induced significant reduction of cell viability and movement capacity. These findings might aid in the understanding of the molecular tumor background as well as development of novel treatment options for advanced penile cancer. Abstract: The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.

Simple Summary The historical standard treatment of metastatic non-small cell lung cancer (NSCLC) consisted of palliative chemotherapy, with limited influence on survival. With the introduction of immuno- and targeted therapy, the prognosis improved largely. A subset of NSCLC patients with limited metastatic disease, called oligometastatic, might obtain long-term survival by adding a local ablative treatment on all visible disease sites, in addition to the standard systemic treatment. The evidence for this combined treatment is still scarce and comes mainly from the pre-immunotherapy era. As radiotherapy might stimulate the immune system making immunotherapy more efficient, here we review the evidence before and in the era of immunotherapy, and discuss the challenges and prospects of the combined treatment. Abstract Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which metastatic cancer should be called “oligometastatic” is unknown, although a consensus definition for oligometastatic disease is proposed by research organizations, such as the EORTC (maximum of five metastases in three organs). Different states of the oligometastatic disease are defined, such as synchronous vs. metachronous, oligopersistent vs. oligoprogressive disease. All clinical trials including patients with non-small cell lung cancer (NSCLC) are small and most are not randomized. Two small randomized phase II trials on synchronous disease showed an improvement in progression free survival, with the addition of LAT, and one also demonstrated an overall survival benefit. Immune checkpoint inhibitors (ICI) were not part of the treatment in these trials, while ICI significantly improved long-term outcomes of patients with metastatic NSCLC. Radiotherapy might improve the prognosis of patients treated with ICI because of its immunostimulatory effects and the possibility to eradicate metastatic deposits. Here, we summarize the data for adding ablative radiotherapy to the treatment of oligometastatic NSCLC, especially in the ICI era, and discuss the challenges of combined treatment.

Contains fulltext : 245204.pdf (Publisher’s version ) (Open Access) AIM: To quantify lymphovascular invasion (LVI) and to assess the prognostic value in patients with pT1b esophageal adenocarcinoma. METHODS: In this nationwide, retrospective cohort study, patients were included if they were treated with surgery or endoscopic resection for pT1b esophageal adenocarcinoma. Primary endpoint was the presence of metastases, lymph node metastases, or distant metastases, in surgical resection specimens or during follow-up. A prediction model to identify risk factors for metastases was developed and internally validated. RESULTS: 248 patients were included. LVI was distributed as follows: no LVI (n = 196; 79.0%), 1 LVI focus (n = 16; 6.5%), 2-3 LVI foci (n = 21; 8.5%) and ≥4 LVI foci (n = 15; 6.0%). Seventy-eight patients had metastases. The risk of metastases was increased for tumors with 2-3 LVI foci [subdistribution hazard ratio (SHR) 3.39, 95% confidence interval (CI) 2.10-5.47] and ≥4 LVI foci (SHR 3.81, 95% CI 2.37-6.10). The prediction model demonstrated a good discriminative ability (c-statistic 0.81). CONCLUSION: The risk of metastases is higher when more LVI foci are present. Quantification of LVI could be useful for a more precise risk estimation of metastases. This model needs to be externally validated before implementation into clinical practice.

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age &lt, 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations.

Highlights • This review discusses 16 studies using 7T MRI to evaluate patients with chronic focal epilepsy. • UHF MRI increases the sensitivity to detect an epileptogenic lesion. • Diagnostic gain of 7T over conventional MRI was between 8 and 67%, pooled gain was 31% • FCD, gliosis and HS were the most frequently diagnosed histopathological lesions. • No conclusion can be drawn whether 7T improves surgical treatment and seizure outcome., Rationale Resective epilepsy surgery is an evidence-based curative treatment option for patients with drug-resistant focal epilepsy. The major preoperative predictor of a good surgical outcome is detection of an epileptogenic lesion by magnetic resonance imaging (MRI). Application of ultra-high field (UHF) MRI, i.e. field strengths ≥ 7 Tesla (T), may increase the sensitivity to detect such a lesion. Methods A keyword search strategy was submitted to Pubmed, EMBASE, Cochrane Database and clinicaltrials.gov to select studies on UHF MRI in patients with epilepsy. Follow-up study selection and data extraction were performed following PRISMA guidelines. We focused on I) diagnostic gain of UHF- over conventional MRI, II) concordance of MRI-detected lesion, seizure onset zone and surgical decision-making, and III) postoperative histopathological diagnosis and seizure outcome. Results Sixteen observational cohort studies, all using 7T MRI were included. Diagnostic gain of 7T over conventional MRI ranged from 8% to 67%, with a pooled gain of 31%. Novel techniques to visualize pathological processes in epilepsy and lesion detection are discussed. Seizure freedom was achieved in 73% of operated patients; no seizure outcome comparison was made between 7T MRI positive, 7T negative and 3T positive patients. 7T could influence surgical decision-making, with high concordance of lesion and seizure onset zone. Focal cortical dysplasia (54%), hippocampal sclerosis (12%) and gliosis (8.1%) were the most frequently diagnosed histopathological entities. Significance UHF MRI increases, yet variably, the sensitivity to detect an epileptogenic lesion, showing potential for use in clinical practice. It remains to be established whether this results in improved seizure outcome after surgical treatment. Prospective studies with larger cohorts of epilepsy patients, uniform scan and sequence protocols, and innovative post-processing technology are equally important as further increasing field strengths. Besides technical ameliorations, improved correlation of imaging features with clinical semiology, histopathology and clinical outcome has to be established.

OBJECTIVE: The objective of this study was to evaluate the long-term predictive value of the Danish Whiplash Group Risk Assessment Score (DWGRAS) with 7 risk strata.DESIGN: E-questionnaire-based follow-up study (n=927) combining 2 cohorts of whiplash-injured patients, 1 observational (n=187) and 1 interventional randomized controlled trial (n=740).METHODS: Nine hundred twenty-seven previously healthy persons exposed to acute whiplash injury during motor vehicle collision were sent letter by postal service asking the addressee if they would respond to an E-questionnaire. Outcome measures were: whiplash-related disability, pain, use of medication/nonmedical treatment, work capacity.RESULTS: The response rate was 37%. Fifty-five percent reported whiplash-related disability. Fourteen percent reported daily symptoms. A strong relationship was found between risk strata and impact of event and between risk strata and disabling symptoms.CONCLUSIONS: Internal and long-term validation of DWGRAS was performed, but a low response rate indicates that results should be interpreted with caution. Furthermore, external validation needs to be done in long-term studies. An receiver operating characteristics curve of 0.73 (95% confidence interval 0.67; 0.79) predicting daily or weekly whiplash-related disability after 12 to 14 years was found using the DWGRAS risk score.

BACKGROUND Information on scintigraphy findings in dogs with thyroid neoplasia is scarce. The use of single-photon emission computed tomography (SPECT) could improve detection of metastatic disease. HYPOTHESIS/OBJECTIVES To describe planar and SPECT imaging findings in dogs with thyroid tumors, and to compare SPECT and thoracic radiography for metastasis detection. ANIMALS Sixty-eight dogs with thyroid neoplasia. METHODS Retrospective study, search of medical records for dogs with thyroid neoplasia (2008-2018). RESULTS Thyroid scintigraphy was available from 68 dogs, of which 6 presented after surgical resection. Radionuclide uptake was increased in 56% of dogs, decreased in 24%, and comparable to that of the salivary glands in 13%. The remainder had multiple masses with variable uptake. A homogeneous uptake pattern was present in 16% and a heterogeneous uptake pattern in 73%. In 11% (all dogs with multiple masses), various uptake patterns were present. Thyroid tumors were well delineated in 55%. There was a significant association between hormone status and uptake pattern (P = .009), with a heterogeneous uptake pattern in the majority of euthyroid dogs, and hormone status and tumor circumscription (P = .003), with well-circumscribed margins in the majority of hypothyroid and hyperthyroid dogs. Thoracic SPECT imaging was available in 39 dogs and identified metastatic lesions in 15 dogs. Thoracic radiographs were performed in 14 of these dogs, and detected metastases in 3 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE SPECT imaging is a viable imaging technique to screen for thoracic metastasis and wider use of SPECT imaging is recommended in dogs with thyroid neoplasia.

Rob AB Oostendorp,1– 4 JW Hans Elvers,5,6 Emiel van Trijffel,7,8 Geert M Rutten,9,10 Gwendolyne GM Scholten-Peeters,11 Marcel Heijmans,4 Erik Hendriks,12,13 Emilia Mikolajewska,14,15 Margot De Kooning,3,16 Marjan Laekeman,17,18 Jo Nijs,3,16,19 Nathalie Roussel,20 Han Samwel21 1Scientific Institute for Quality of Healthcare, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; 2Department of Manual Therapy, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium; 3Pain in Motion International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium; 4Practice Physiotherapy and Manual Therapy, Heeswijk-Dinther, the Netherlands; 5Department of Public Health and Research, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; 6Department of Allied Health Care, Methodological Health-Skilled Institute, Beuningen, the Netherlands; 7Department of Master Education, SOMT University of Physiotherapy, Amersfoort, the Netherlands; 8Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium; 9Institute of Health Studies, Faculty of Health and Social Studies, HAN University of Applied Science, Nijmegen, the Netherlands; 10Campus Venlo, Faculty of Science and Engineering, Maastricht University, Maastricht, the Netherlands; 11Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands; 12Department of Epidemiology, Center of Evidence Based Physiotherapy, Maastricht University, Maastricht, the Netherlands; 13Practice Physiotherapy ‘Maasstaete, Druten, the Netherlands; 14Department of Physiotherapy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland; 15Neurocognitive Laboratory, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń, Poland; 16Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium; 17Department of Nursing Sciences, Ph.D.-Kolleg, Faculty of Health, University Witten/Herdecke, Witten, Germany; 18Department of Physiological Psychology, University of Bamberg, Bamberg, Germany; 19Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden; 20Department of Physiotherapy and Rehabilitation Sciences (MOVANT), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; 21Revalis Pain Rehabilitation Centre, S Hertogenbosch, the NetherlandsCorrespondence: Rob AB OostendorpScientific Institute for Quality of Healthcare, Radboud University Nijmegen Medical Centre, p/a Oude Kleefsebaan 325, AT Berg En Dal 6572, Nijmegen, the NetherlandsTel +31 246423419Email oostendorp.rob@gmail.comBackground: Whiplash-associated disorders (WADs) constitute a state of health characterized by a wide diversity of symptoms as a result of impairments of functions, activity limitations, and participation restrictions. Patient-reported outcome measurements (PROMs) and patient-reported outcomes (PROs) seem appropriate when describing and evaluating the health status of patients with WAD.Aim: To measure the use of PROMs and PROs as quality indicators in clinical reasoning, and to analyze and evaluate pre- and post-treatment ‘pain intensity’ and ‘functioning’, and for ‘perceived improvement’ in patients with WAD in primary care physiotherapy practice by year of referral, with the phase after accident and prognostic health profile embedded in the clinical reasoning process.Materials and Methods: Data were collected over a period of 10 years. Pain intensity, functioning, and perceived improvement were measured using the Visual Analogue Scale for Pain (VAS-P), the Neck Disability Index (NDI) and the Global Perceived Effect scale (GPE). Pre- and post-treatment mean differences were tested for statistical significance and compared to minimal clinically important differences (MCID). Effect sizes were expressed as Cohen’s d. Multivariable regression analysis was performed to explore independent associations of year of referral, phase after the accident, and the patient’s prognostic health profile with post-treatment pain intensity and functioning.Results: A consecutive sample of 523 patients was included. Pre- and post-treatment mean differences on VAS-P and NDI were statistically significant (P< 0.000) and clinically relevant, with ‘large’ effect sizes for pain intensity and functioning. MCIDs were achieved by 80% for VAS-P and for 60% for NDI. Year of referral and phase after the accident were independently associated with worse post-treatment functioning. About half of the patients (n=241 [46.1%]) perceived themselves as improved.Conclusion: The PROMs and PROs pain intensity, functioning and perceived improvement were integrated as quality indicators in the physiotherapy clinical reasoning process for patients with WAD. Significant differences in pain intensity and functioning were found but were unrelated to year of referral, phase after whiplash-related injury or prognostic health profile. The MCID VAS-P scores did not differ depending on experienced pain.Keywords: whiplash-Associated Disorders, neck pain, physiotherapy, patient-reported outcomes measures, routinely collected data

Preclinical and early clinical evidence suggest that radical radiotherapy of oligometastatic disease in non-small cell lung cancer (NSCLC) patients can impact outcomes with relatively limited toxicity. Whilst data from phase 2 randomized trials suggesting an improved overall survival (OS) with this treatment is promising, it has also illustrated the heterogeneity in this patient population and treatment. Oligometastatic disease in itself comprises a broad spectrum of patients, in terms of tumor load and location, stage of the disease and treatment history. This real-life variety in patient characteristics is often reflected in studies to a certain extent, hinting to the fact that all might benefit from radical radiotherapy to limited metastatic disease, yet leaving the question unanswered as to whom the ideal candidate is. Furthermore, differences between and within studies with regards to treatment modality, timing, radiation technique, and radiation dose are substantial. Also, preclinical and early clinical trials suggest that radiotherapy can work synergistically with checkpoint inhibitors by acting as an in situ cancer vaccine, therefore the combination of these two treatments in oligometastatic patients might entail the largest benefit. Ongoing randomized controlled phase 3 trials and prospective registry trials will further elucidate the true extent of benefit of this local treatment strategy and aid in identifying the ideal patient population and therapy. The current narrative review summarizes the clinical evidence on radiotherapy for oligometastatic NSCLC and highlights the remaining unknowns.

Supplemental Digital Content is Available in the Text. Stress mediated the effect of a physiotherapist-delivered integrated intervention on multiple health outcomes and pain-related coping mediated the effect on pain self-efficacy only. Changes in depressive and posttraumatic stress symptoms were also mechanisms of effect., Introduction: Integrated psychological and physical treatments can improve recovery for whiplash-associated disorders (WADs). Little is known about how these interventions work. Objective: To examine the mechanisms by which a physiotherapist-delivered integrated intervention for acute WAD improves health outcomes. Methods: Secondary analysis using structural equation modelling of a randomized controlled trial comparing integrated stress inoculation training and exercise to exercise alone for acute WAD. Outcomes were disability, pain self-efficacy, pain intensity, and health-related quality of life at 12 months. The intended intervention target and primary mediator, stress was tested in parallel with pain-related coping, an additional cognitive behavioral mediator that significantly improved at posttreatment (Model 1). Stress-related constructs that commonly co-occur with stress and pain were also tested as parallel mediators: depression and pain-related coping (Model 2); and posttraumatic stress and pain-related coping (Model 3). Results: Reductions in stress mediated the effect of the integrated intervention on disability (β = −0.12, confidence interval [CI] = −0.21 to −0.06), pain self-efficacy (β = 0.09, CI = 0.02–0.18), pain (β = −0.12, CI = −0.21 to −0.06), and health-related quality of life (β = 0.11, CI = 0.04–0.21). There was an additional path to pain self-efficacy through pain-related coping (β = 0.06, CI = 0.01–0.12). Similar patterns were found in Models 2 and 3. Conclusions: Improvements in stress and related constructs of depression and posttraumatic stress, and pain-related coping were causal mechanisms of effect in a physiotherapist-delivered integrated intervention. As integrated interventions are growing in popularity, it is important to further personalize interventions for improved benefit.

Objective The aim of this study was to determine whether the extent of peritoneal metastases (PMs) on preoperative diffusion-weighted magnetic resonance imaging (DW-MRI) can be used as a biomarker of disease-free and overall survival in patients with colorectal cancer who are considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Methods For this retrospective cohort study, patients with PMs considered for CRS/HIPEC who underwent DW-MRI for preoperative staging in 2016-2017 were included. The DW-MRI protocol consisted of diffusion-weighted, T2-weighted, and pre- and post-gadolinium T1-weighted imaging of the chest, abdomen, and pelvis. DW-MRI images were evaluated by two independent readers to determine the extent of PMs represented by the Peritoneal Cancer Index (MRI-PCI), as well as extraperitoneal metastases. Cox regression and Kaplan-Meier analysis was performed to determine the prognostic value of DW-MRI for overall and disease-free survival. Results Seventy-eight patients were included. CRS/HIPEC was planned for 53 patients and completed in 50 patients (60.5%). Median follow-up after DW-MRI was 23 months (interquartile range 13-24). The MRI-PCI of both readers showed prognostic value for overall survival, independently of whether R1 resection was achieved (hazard ratio [HR] 1.06-1.08; p

Purpose: We aim to establish the prognostic value of metabolic parameters of the primary tumor in patients diagnosed with vulvar squamous cell carcinoma (VSCC) who underwent a pretreatment F-18 FDG PET/CT scan. Materials and methods: This retrospective study included 47 patients with a his topathologically confirmed diagnosis of VSCC, and who underwent a F-18 FDG PET/CT scan prior to treatment. The disease stage and age at diagnosis, the maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (WV) and total lesion glycolysis (TLG) values of the primary tumor, based on a baseline PET scan, were recorded. The relationship between these factors, and progression-free survival (PFS) and overall survival (OS) was evaluated. Results: The mean age of the 47 study patients was 69.6 +/- 1.9 years. Among the patients, 18 were in early stage of the disease and 29 were in the advanced stage. The age, and SUVmax, SUVmean, MTV and TLG values were statistically significantly associated with OS and PFS. Furthermore, it was noted that OS and PFS were significantly longer in the early stage patients than in the advanced stage patients, in patients with a tumor size >= 4 cm than those with a tumor size 4 cm, and in patients with a negative lymph node metastasis than those with a positive lymph node metastasis. Conclusion: Our findings suggest that PET parameters are prognostic factors for VSCC. To the best of our knowledge, this study is the first to investigate the prognostic value of the PET parameters of primary tumors in patients with VSCC, and as such, we believe it contributes to literature. (C) 2020 Sociedad Espanola de Medicina Nuclear e Imagen Molecular. Published by Elsevier Espana, S.L.U. All rights reserved.

Introduction: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process.Methods: A pan-European multidisciplinary consensus group was established. Consensus questions were built on the basis of current controversies, and definitions were extracted from a survey, cases and a systematic review. This statement was formulated during a consensus meeting.Results: It was determined that definition of sOM NSCLC is relevant when a radical treatment that may modify the disease course (leading to long-term disease control) is technically feasible for all tumor sites with acceptable toxicity. On the basis of the review, a maximum of five metastases and three organs was proposed. Mediastinal lymph node involvement was not counted as a metastatic site. Fludeoxyglucose F 18 positron emission tomography-computed tomography and brain imaging were considered mandatory. A dedicated liver magnetic resonance imaging scan was advised for a solitary liver metastasis, and thoracoscopy and biopsies of distant ipsilateral pleural sites were recommended for a solitary pleural metastasis. For mediastinal staging, fludeoxyglucose F 18 positron emission tomography-computed tomography was deemed the minimum requirement, with pathological confirmation recommended if this influences the treatment strategy. Biopsy of a solitary metastatic location was mandated unless the multidisciplinary team is of the opinion that the risks outweigh the benefits.Conclusion: A multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.