Tangential beam IMRT versus tangential beam 3D-CRT of the chest wall in postmastectomy breast cancer patients: A dosimetric comparison

<p>Abstract</p> <p>Background</p> <p>This study evaluates the dose distribution of reversed planned tangential beam intensity modulated radiotherapy (IMRT) compared to standard wedged tangential beam three-dimensionally planned conformal radiotherapy (3D-CRT) of the chest wall in unselected postmastectomy breast cancer patients</p> <p>Methods</p> <p>For 20 unselected subsequent postmastectomy breast cancer patients tangential beam IMRT and tangential beam 3D-CRT plans were generated for the radiotherapy of the chest wall. The prescribed dose was 50 Gy in 25 fractions. Dose-volume histograms were evaluated for the PTV and organs at risk. Parameters of the dose distribution were compared using the Wilcoxon matched pairs test.</p> <p>Results</p> <p>Tangential beam IMRT statistically significantly reduced the ipsilateral mean lung dose by an average of 21% (1129 cGy versus 1437 cGy). In all patients treated on the left side, the heart volume encompassed by the 70% isodose line (V70%; 35 Gy) was reduced by an average of 43% (5.7% versus 10.6%), and the mean heart dose by an average of 20% (704 cGy versus 877 cGy). The PTV showed a significantly better conformity index with IMRT; the homogeneity index was not significantly different.</p> <p>Conclusions</p> <p>Tangential beam IMRT significantly reduced the dose-volume of the ipsilateral lung and heart in unselected postmastectomy breast cancer patients.</p

Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression

<p>Abstract</p> <p>Background</p> <p>Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention.</p> <p>Methods</p> <p>The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.</p> <p>Trial registration</p> <p>Local Ethics Committee: H-KF 307413</p> <p>Danish Medicines Agency: 2612-3162.</p> <p>EudraCT: 2006-001750-28.</p> <p>Danish Data Agency: 2006-41-6737.</p> <p>ClinicalTrials.gov: NCT 00386841</p

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

19 Overall survival after surgical staging by lymph node dissection versus sentinel lymph node biopsy in endometrial cancer: a national cancer database study

Objectives To investigate the association between the type of lymph node (LN) assessment and overall survival (OS) in endometrial cancer (EC). Methods Patients with stage I-III EC who underwent a hyster- ectomy and LN assessment from 2012 to 2015 were identi- fied from the National Cancer Database. Multivariable Cox proportional hazards regression analysis was performed to assess factors associated with OS. Results Of 68,614 patients identified, 64,796 underwent lym- phadenectomy (LND) only, 1,777 sentinel lymph node biopsy only (SLN-B), and 2,041 both procedures (SLN-B/LND). On multivariable analysis, SLN-B and SLN-B/LND were not associ- ated with different OS compared to LND (hazard ratio [HR]: 0.92; 95%CI: 0.73–1.17 - HR: 0.91; 95%CI: 0.77–1.07,respectively). Similarly, when stratified by LN status, SLN-B and SLN-B/LND reported similar OS compared to LND, both in negative (HR: 1.03; 95%CI: 0.85–1.26 – HR :0.95; 95% CI: 0.73–1.23, respectively) and positive (HR: 0.92; 95%CI: 0.55–1.54 – HR: 0.76; 95%CI: 0.57–1.03, respectively) LNs. Including only LND with !10 pelvic and !1 para-aortic LNs removed, no difference in OS was observed between LND and SLN-B or SLN-B/LND in the entire cohort, and in nega- tive or positive LNs. In all analyses, older age, Charlson-Deyo Score !2, black race, higher American Joint Committee on Cancer (AJCC) pathologic T stage, grade 3, presence of lym- phovascular infiltration, type-2 histology, and absence of che- motherapy or radiation therapy were independently associated with worse OS. Conclusions When compared to SLN-B or SLN-B/LND, LND does not appear to improve OS in EC, even in the presence of LN metastases

Adoption of Minimally Invasive Surgery and Decrease in Surgical Morbidity for Endometrial Cancer Treatment in the United States

To assess how the widespread adoption of minimally invasive surgery in the United States is associated with changes in 30-day morbidity and mortality in endometrial cancer treatment.OBJECTIVE: To assess how the widespread adoption of minimally invasive surgery in the United States is associated with changes in 30-day morbidity and mortality in endometrial cancer treatment. METHODS: In this retrospective cohort study, the American College of Surgeons' National Surgical Quality Improvement Project database for 2008-2014 was reviewed for patients who had undergone surgery for endometrial cancer according to their primary Current Procedural Terminology (CPT) codes. Women with CPT codes for advanced cancer or with disseminated disease were excluded. A trend analysis across the time period by surgical approach (open surgery through laparotomy, vaginal surgery, and minimally invasive surgery) was performed using a Cochran-Armitage test for trend. Thirty-day surgical outcomes were compared between patients who had minimally invasive surgery and open surgery. Inverse probability of treatment weighting models were used to investigate the independent effect of minimally invasive surgery on 30-day outcomes.RESULTS: Overall, 12,283 patients met the inclusion criteria. A significant implementation of minimally invasive surgery (24.2-71.4%) and a concomitant decrease in open surgery through laparotomy (71.1-26.4%) were observed from 2008 to 2014 (both P&lt;.001). Rate of vaginal surgery did not change over time (1.5-2.2%, P=.06). After adjusting for possible confounders, open surgery (compared with minimally invasive surgery) was independently associated with increased odds of major complications (n=347 versus n=274, adjusted odds ratio [OR] 2.4, 95% CI 2.0-2.8), readmission (n=269 versus n=238, adjusted OR 2.2, 95% CI 1.8-2.6), reoperation (n=80 versus n593, adjusted OR 1.5, 95% CI 1.2-2.1), superficial surgical site infection (n=190 versus n=55, adjusted OR 6.8, 95% CI 5.0-9.2), perioperative transfusion (n=430 versus n=149, adjusted OR 5.9, 95% CI 4.8-7.1), and death (n=41 vs, n=20, adjusted OR 3.8, 95% CI 2.2-6.6). A comprehensive decrease in 30-day morbidity for the treatment of endometrial cancer overall was observed from 2008 to 2014 (P&lt;.001), whereas 30-daymortality remained stable (P=.24).CONCLUSION: The widespread adoption of minimally invasive surgery is associated with substantial decreases in 30-day morbidity, readmission, and reoperation for women treated for endometrial cancer in the United States