11 research outputs found

    Increasing Radiation Dose to the Thoracic Marrow Is Associated With Acute Hematologic Toxicities in Patients Receiving Chemoradiation for Esophageal Cancer

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    Purpose: To test the hypothesis that increasing radiation dose to the thoracic marrow (TM) contributes to the development of hematologic toxicities (HT) in esophageal cancer (EC) patients receiving chemoradiation therapy (CRT).Methods: We identified EC cases treated with curative intent CRT at our institution from 2007 to 2016. The TM was contoured as the union of the vertebral bodies (VB) from T1-L1, the ribs from T1-L1, and the sternum. The TM-mean dose and the TM volume receiving at least 5–50 Gy (V5-V50) were collected. Grade ≥ 3 HT (HT3+) was the primary endpoint. Normal tissue complication probability (NTCP) was evaluated using the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT3+ and dosimetric parameters. Odds ratios (OR) and 95% confidence intervals (CI) are reported with p < 0.05 considered significant. Receiver operating characteristics analysis was used to determine optimal cut points.Results: We identified 137 EC cases, and most received concurrent carboplatin/paclitaxel (N = 83). Median radiation dose was 50.4 Gy (IQR = 50.4–50.4 Gy). The rate of HT3+ was 39.4%. Optimization of the LKB model yielded the results n = 0.70, m = 0.67, and TD50 = 20.1 Gy. The TM-V30 was most strongly associated with HT3+ and on multivariate analysis, patients with TM-V30 ≥ 14% had a 5.7-fold (95% CI 2.42–14.54, p < 0.001) increased odds of HT3+ in the entire cohort and a 4-fold (95% CI 1.54–11.11, p = 0.006) increased odds of HT3+ in the carboplatin/paclitaxel cohort compared to patients with TM-V30 < 14%. Radiation dose to the VB and rib sub-sites of the TM were also associated with HT3+, particularly VB-V40.Conclusion: We found that increasing TM radiation dose was associated with HT3+ in EC patients treated with CRT. Radiation dose to the VB and rib sub-sites were also associated with HT3+. These findings suggest that limiting radiation dose to the TM (or its sub-sites) may be sufficient to decrease HT3+, but further prospective evaluation of these results is needed

    Coeliac plexus radiosurgery for pain management in patients with advanced cancer : study protocol for a phase II clinical trial

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    Introduction: Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer. Methods and analysis: A single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association. Ethics and dissemination: Ethic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications. Trial registration number: NCT03323489

    Seminoma

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    Prior to treatment, an adequate staging workup should be performed. Complete H&P including scrotal and testicular examination, serum tumor markers (α-fetoprotein, β-human chorionic gonadotropin, and LDH), scrotal ultrasound, CT of the abdomen and pelvis, and CX

    The E2F1/Rb and p53/MDM2 pathways in DNA repair and apoptosis: understanding the crosstalk to develop novel strategies for prostate cancer radiotherapy

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    Both the p53- and E2F1-signaling pathways are defective in almost all types of tumors, suggesting very important roles for their signaling networks in regulating the process of tumorigenesis and therapy response. Studies on Radiation Therapy Oncology Group tissue samples have identified aberrant expression of p53, MDM2 (an E3 ubiquitin ligase that targets p53 for proteosomal degradation), and p16 (an upstream regulator of retinoblastoma and hence E2F1 in prostate cancer); abnormal expression of these biomarkers has been associated with clinical outcome after radiotherapy ± androgen deprivation therapy. Although the proapoptotic properties of p53 are well documented, a relatively new aspect of p53 function as an active mediator of prosurvival signaling pathways is now emerging. E2F1 is a transcription factor that possesses both proapoptotic and prosurvival properties. Thus, the role of E2F1 in the process of tumorigenesis versus apoptosis is a contested issue that needs to be resolved. Furthermore, the role of E2F1 in DNA repair is being increasingly recognized. Thus, novel approaches to curb the prosurvival and DNA repair capability of E2F1 while promoting apoptotic function are of interest. In this review, we discuss the challenges involved in targeting the p53/E2F1 pathways and the crosstalk networks, and further propose potential therapeutic strategies for prostate cancer management

    Prognostic impact of clinical tumor size on overall survival for subclassifying stages I and II vaginal cancer: A SEER analysis

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    This study accessed the Surveillance, Epidemiology and End Results (SEER) database to determine if tumor size is an independent predictor of overall survival (OS) for patients with stages I and II vaginal cancer (VC). We identified in the SEER database, patients with available tumor size having stage I or II squamous cell histology from January 2004 through December 2012 with minimum follow-up of six months. Univariate analyses (UA) and multivariable analyses (MVA) evaluated the effect of several prognostic factors, including tumor size, regarding OS. 529 SEER patients were found with recorded tumor sizes, of which 293 (55.4%) were stage I and 236 (44.6%) stage II. UA found the following significant prognostic factors of worse OS: tumor size >2cm (HR=1.80, p=0.02) and older age at diagnosis (p2cm (HR=2.13, p=0.04) and older age at diagnosis (p2cm were 79.2% vs. 66.1% in stage I (p=0.0187) and 80.9% vs. 51.2% in stage II (p=0.0369). MVA confirmed about double risk of death for patients with tumor size >2cm (HRs: 1.88 in stage I and 2.06 in stage II). Tumor size seems to predict OS outcome in patients with stages I/II VC. Further confirmatory investigations are recommended to firmly establish its incorporation into currently accepted staging criteria for these patients. •A review of patients with stage I/II vaginal cancers was performed.•Data was obtained from a national population-based repository.•Multivariable analyses found tumor size was an independent predictor of survival.•Confirmatory investigations are needed before revising existing staging systems

    A Tissue Biomarker–Based Model That Identifies Patients with a High Risk of Distant Metastasis and Differential Survival by Length of Androgen Deprivation Therapy in RTOG Protocol 92-02

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    PURPOSE: To examine the relationship between the expression of 7 promising apoptotic/cell proliferation proteins (Ki-67, p53, MDM2, bcl-2, bax, p16, and Cox-2) and risk of distant metastasis (DM). EXPERIMENTAL DESIGN: RTOG 92-02 compared external beam radiotherapy (EBRT) to ~70 Gy+short term androgen deprivation therapy (STADT) with EBRT+long term ADT (LTADT). Immunohistochemical analysis was available for ≥4 biomarkers in 616 of 1521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of DM using competing risks hazards regression, adjusting for age, PSA, Gleason score, T-stage, and treatment. RESULTS: Modeling identified four biomarkers (Ki-67, MDM2, p16 and Cox-2) that were jointly associated with DM. The c-index was 0.77 for the full model and 0.70 for the model without the biomarkers; a relative improvement of about 10% (likelihood ratio p < 0.001). Subdivision of the patients into quartiles based on predicted DM risk identified a high risk group with 10-year DM risk of 52.5% after EBRT+STADT and 31% with EBRT+LTADT; associated 10-year prostate cancer specific mortality (PCSM) risks were 45.9% and 14.5% with STADT and LTADT. CONCLUSION: Four biomarkers were found to contribute significantly to a model that predicted DM and identified a subgroup of patients at a particularly high risk of both DM and PCSM when EBRT+STADT was used. LTADT resulted in significant reductions in DM and improvements in PCSM, and there was a suggestion of greater importance in this very high risk subgroup

    Promoting Women and Historically Excluded Minorities in Medicine as Essential Leaders of Research

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    Women and historically excluded minorities are underrepresented in clinical research. At the ASTRO 2021 annual meeting, the authors reviewed several strategies to improve on this issue. Implementation of such strategies should not only improve their visibility but also provide increased opportunities for their advancement and work in clinical research
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