Pre- and Post-therapy Risk Factors for Vasculopathy in Pediatric Craniopharyngioma Patients Treated with Surgery and Proton Radiotherapy

2022 ◽  
Author(s):  
John T. Lucas ◽  
Austin M. Faught ◽  
Chih Yang Hsu ◽  
Lydia J. Wilson ◽  
Yian Guo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Proton Radiotherapy ◽  
Post Therapy

Risk Factors For Radiation Pneumonitis In Patients With Lymphoma Treated With Chemotherapy and Photon Or Proton Radiotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5101-5101
Author(s):  
Anna Mesina ◽  
Surbhi Grover ◽  
Carmen Mesina ◽  
Sunita D. Nasta ◽  
Jakub Svoboda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hodgkin Lymphoma ◽  
Radiation Pneumonitis ◽  
Combined Modality Therapy ◽  
Proton Radiotherapy ◽  
Lung Dose ◽  
Non Hodgkin Lymphoma ◽  
Combined Modality ◽  
Dose Volume ◽  
Higher Doses

Abstract Introduction As volume-based radiotherapy planning has become a more standard part of combined modality therapy for lymphomas, dose-volume based constraints for organs-at-risk are needed for treatment planning. Conformal techniques such as intensity modulated radiation therapy and proton radiotherapy may achieve lower doses to certain organs like the heart, but may result in higher doses to other tissues like the lungs and breasts. We sought to define the dosimetric risk factors that are associated with development of radiation pneumonitis (RP). Methods This is a single-institution retrospective analysis of patients with thoracic lymphomas treated with combined modality therapy between 1999 and 2013 who had at least 4 months of follow-up after radiotherapy. Univariate analyses (UVA) were performed using Fisher exact and Wilcoxon rank-sum tests. Results Of the 89 patients analyzed, 13 (14.6%) were diagnosed with RP (at least Grade 1, Common Toxicity Criteria v4.0). Patients were predominantly female (62%) and never smoked (67%). Diagnoses were grouped as Hodgkin lymphoma (62.9%) or non-Hodgkin lymphoma (37.1%), and 18.5% were also treated with autologous stem cell transplants. UVA showed that RP was more commonly associated with a diagnosis of non-Hodgkin lymphoma (38%) than Hodgkin lymphoma (8%), despite exposure to bleomycin in the majority of patients with Hodgkin lymphoma. Higher lung doses were significantly associated with RP using multiple lung dose-volume parameters: mean lung dose (12.3 vs. 16.7 Gy, p=0.002), volume of lung receiving 20 Gy (27.3% vs. 39.1%, p=0.0009), and volume of lung receiving 5 Gy (51% vs. 66.8%, p=0.004). The majority (67%) of patients who developed RP had mean lung doses of over 15 Gy, whereas only 24% of those who did not develop RP had mean lung doses above 15 Gy, see Figure. Heart dosimetric parameters were also significantly associated with RP, including mean heart dose (13.3 vs. 21.5 Gy, p=0.004), volume of heart receiving 20 Gy (25.4% vs. 48.3%, p=0.003), and volume of heart receiving 5 Gy (57.6% vs. 81.1%, p=0.04). There were not enough events to determine if heart and lung parameters were independently associated with RP, but they were strongly correlated (R=0.75). Gender, smoking history, and autologous transplant were not significantly associated with RP. None of the 13 patients treated with proton radiotherapy developed RP. In general, patients treated with proton radiotherapy had lower mean heart doses (9.4 vs. 15.4 Gy) and mean lung doses (9.6 Gy vs. 13.5 Gy). Conclusions Higher doses to lung and heart are associated with increased risk of RP, and doses to these critical structures should be considered carefully during volume-based consolidative radiotherapy using advanced techniques. Disclosures: No relevant conflicts of interest to declare.

Liquid Biopsy In Stage Iv Non-Small Cell Lung And Prostate Cancers And Prevalence Of Ethnicity And Risk Factors: A Va Medcial Center Experience

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S145-S145
Author(s):  
S Dalal ◽  
D Jhala
Keyword(s):  
Risk Factors ◽  
African American ◽  
Risk Factor ◽  
Liquid Biopsy ◽  
Patient Population ◽  
Advanced Nsclc ◽  
Therapy Response ◽  
Agent Orange ◽  
Prostate Cancers ◽  
Post Therapy

Abstract Introduction/Objective The advent of Liquid biopsy (LB) is a milestone in precision oncology. This minimally invasive revolutionary technique analyses circulating tumor DNA and detects signature genomic alterations. Advanced-stage prostate cancers are more common in African Americans both in general and veteran patient population, while general cohort Caucasians are more prone to advanced/metastatic NSCLC. Risk factor for these cancers is smoking; agent orange exposure and its relationship with aggressiveness/ethnicity for veterans is sparse in the literature. We performed a QA study for advanced lung/prostate cancers of veteran patients on LB. Methods QA documentation from Foundation One (Cambridge MA, NGS) on LB performed for the regional Veteran Affairs Medical Center (VAMC) from May 2019 to April 2020 were reviewed. The testing was performed on advanced NSCLC/prostate cancer cases with evidence of advanced tumor progression. Data for ethnicity, risk factors, post therapy PSA, Gleason score and genetic mutations noted. Results A total of 30 LBs were performed over this time period. Of 30 LBs, 23 were prostate and 7 were lung cancers. 2/30 had unknown ethnic background. 19/28 (67.8%) were of African American origin, 18 of which had advanced prostate cancers. 11/28 were white, of which 3/30 were advanced NSCLC. One patient declined to reveal risk factor exposure, hence 17/29 (58.6%) had smoking, 15/29 (51.7%) had a risk of herbicide, agent orange exposure; and, 10/29 (34.4%) had both risk factor exposures. 6/29 (20.6%) African American veterans had combined risk factors. 9/10 (90%) veterans which had dual exposure presented with either Gleason score of 9 or as metastasis. Post therapy PSA ranged from 0.5 to 1870 ng/ml and did not corelate with the aggressiveness of the cancer or therapy response. Conclusion Veteran patient population has slightly higher incidence of ethnic African Americans presenting with advanced NSCLC/prostate cancers compared to general patient cohort. Although incidence of smoking is similar, combined exposure with agent orange, increases the aggressiveness of the disease three-fold. Real-time monitoring of the therapy response and multimodal benefits by LB is of immense help in morbidly ill veterans, compared to post- therapy PSA monitoring or invasive tissue biopsy. Role of LB should also be explored for early screening/triaging the veterans.

Other Cancers in Patients with Chronic Lymphocytic Leukemia Requiring Therapy: Association with Prognostic Factors and Impact On Survival

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3896-3896
Author(s):  
Lorenzo Falchi ◽  
Michael J. Keating ◽  
Susan Lerner ◽  
Xuemei Wang ◽  
Sara S. Strom ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Median Time ◽  
Causes Of Death ◽  
Stem Cell Transplant ◽  
Lymphocytic Leukemia ◽  
Cell Transplant ◽  
Post Therapy

Abstract Abstract 3896 Chronic lymphocytic leukemia (CLL) is associated with an increased incidence of other cancers (OC). Potential risk factors for OC in CLL include immune disturbances, shared risk factors, genetic predisposition and chemotherapy. While reports on OC in patients with CLL have been typically descriptive in nature, detailed information regarding the clinical features of OC, relationship with the time of diagnosis of CLL, patient characteristics, prognostic factors and survival have been missing. We report an analysis of OC in pts with CLL requiring therapy, with a post therapy observation time of 5 years or longer. We reviewed our database and selected pts with CLL seen at our center who underwent treatment and who have a follow-up of at least 5 years after therapy. We studied pts with an OC either before or after the diagnosis and/or treatment of CLL and compared them with patients without OC. Richter's transformation of CLL was not considered an OC in this analysis. A total of 1,364 pts with CLL referred between 1963 and 2007 with a median follow up time of 8.2 years (range 5–28) were studied. Among these, we identified 324 pts (24%) with OC. Sixty-eight pts were diagnosed with >1 OC [2 OC (62 pts), 3 OC (4 pts) or 4 OC (2 pts)], for a total of 400 individual OC. Of the 324 pts with OC, OC preceded the diagnosis of CLL in 117 pts (36%), with a median time from OC to CLL of 80 (0–455) months, OC occurred after the diagnosis of CLL but before treatment in 49 pts (15%), with median time from CLL to OC of 22 (0–131) months. OC occurred after treatment of CLL in 158 pts (49%), with a median time from treatment to OC of 94 (0–304) months. The type, frequency and timing of OC are summarized in table 1. Clinical characteristics and traditional prognostic factors were not significantly different between pts with and without OC, with the exception of age, as pts with OC are older than pts without OC at the time of referral (median age: 60 vs 55 years, p<.0001). We next analyzed the distribution of the newer prognostic parameters in these two groups. Fifty-three % of pts with OC had unmutated IGHV genes, 65% were ZAP70+, 22% CD38+, 8% had del17p, 27% del11q, 22% +12, 20% negative FISH, and 23% del13q. Sixty-one % of pts without OC had unmutated IGHV genes, 58% were ZAP70+, 26% CD38+, 6% had del17p, 17% del11q, 22% +12, 26% negative FISH, and 29% del13q. A trend toward significance (p.07) for a higher incidence of del11q was observed in pts with OC. At the time of this analysis 536 (39%) pts have died and 828 (61%) are alive. One hundred seventy six/324 (54%) pts with OC are alive, vs 652/1040 (63%) pts without OC (p<.007). Median overall survival (OS) has not been reached in either pt group at a median follow up of 95 (61–284) months for pts with OC and 98 (61–340) months for pts without OC. Causes of death were: progression of CLL (99), CLL-related complications (121), OC (43), complications of stem cell transplant (16), events unrelated to CLL (39) and unknown causes (218). In pts with OC, the OC itself was the cause of death in 37%. Other causes of death were CLL/CLL-related complications in 44%, complications of stem cell transplant in 8%, and events unrelated to CLL in 11%. In contrast, in pts without OC CLL/CLL-related complications accounted for 83% of deaths, complications of stem cell transplant for 4%, and events unrelated to CLL for 13%. In conclusion, in pts with CLL requiring therapy and with post therapy follow up of >5 years, the incidence of OC is 24%. Among pts with OC, there is a trend for higher number of pts with del11q. In pts with OC, OC itself is a major cause of death, while the vast majority of deaths among pts without OC are caused by CLL or CLL-related complications. Table 1. Distribution of OC (1364 pts). Site of OC 1st case Total cases OC prior/at CLL OC after CLL After diagnosis After treatment NMSC1 124 144 41 26 77 PROSTATE 43 54 18 7 29 MELANOMA 26 34 16 2 16 BREAST 23 26 14 2 10 MDS/AML2 16 18 0 0 18 LUNG 14 21 0 1 20 NEUROENDOCRINE 3 6 1 0 5 HEAD AND NECK 12 16 3 2 11 UROTHELIAL CELL CANCERS 11 12 7 2 3 GI3 (including pancreas and liver) 10 18 4 3 11 KIDNEY 10 11 4 3 4 NHL4 and MM5 8 12 0 0 12 TESTIS/OVARY 6 6 4 0 2 THYROID 6 7 5 1 1 SARCOMAS 4 5 4 0 1 UTERUS 2 3 3 0 0 OTHERS6 6 7 3 0 4 TOTALS 324 400 127 49 224 1 non-melanoma skin cancers; 2 myelodysplastic syndrome/acute myeloid leukemia; 3 gastrointestinal; 4 non-Hodgkin's lymphoma; 5 multiple myeloma; 6 includes: brain, nasopharyngeal, penis carcinoma, mesothelioma, unknown primary. Disclosures: No relevant conflicts of interest to declare.

THU0279 PREVALENCE AND RISK FACTORS OF HERPES ZOSTER REACTIVATION IN PATIENTS WITH BIOPSY PROVEN LUPUS NEPHRITIS UNDERGOING IMMUNOSUPPRESSIVE THERAPIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 366-367
Author(s):  
C. C. Mok ◽  
S. M. Tse ◽  
K. L. Chan ◽  
L. Y. Ho
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Herpes Zoster ◽  
Renal Disease ◽  
Renal Biopsy ◽  
Immunosuppressive Drugs ◽  
Daily Dose ◽  
First Time ◽  
Immunoglobulin Levels ◽  
Post Therapy

Background:Herpes zoster (HZ) reactivation is fairly common in patients with systemic lupus erythematosus (SLE). However, there is a paucity of studies that reported the risk factors of HZ reactivation in well-defined subsets of SLE patients.Objectives:To study the prevalence of HZ reactivation in patients with active biopsy confirmed lupus nephritis (LN) undergoing immunosuppressive therapies.Methods:Patients who had biopsy proven active LN that was treated with immunosuppressive regimens in our unit between 2003 and 2018 were retrospectively reviewed for the occurrence of HZ reactivation within 2 years’ therapies. HZ was a clinical diagnosis based on history and physical signs by attending physicians. The following were collected: age and SLE duration at renal biopsy, sex, SLE disease activity scores, maximum daily dose and total duration of high-dose prednisolone and other immunosuppressive drugs in the induction period, maintenance therapies, laboratory parameters at renal biopsy and 6 months post-therapy that included lupus serology, albumin, globulin, immunoglobulin levels (IgG/A/M) and white cell counts (lymphocyte and neutrophil), histological classes of LN and clinical response at 6 month and 2 years. The incidence of HZ reactivation within 2 years of active LN treatment and the total prevalence of HZ infection over time until last follow-up was calculated. Risk factors for HZ reactivation were studied by logistic regression.Results:251 patients with 311 episodes of active LN were studied (92% women; age 34.2±14.2 years at first renal biopsy). The distribution of histological classes (WHO or ISN/RPS) was: class III/IV±V (69%), I/II/V/VI (31%). First-time renal disease occurred in 61% of patients. Induction treatment regimens were: prednisolone in combination with CYC (17%), azathioprine (11%), MMF (42%), tacrolimus (25%). Within 2 years of immunosuppressive therapies, 55 (18%) episodes of LN were complicated by HZ infection. The incidence of HZ reactivation was 8.84/100 patient-year. The median time for HZ reactivation since LN treatment was 11 months. 28 patients had HZ infection occurring longer than 2 years post-therapy, giving an overall prevalence of 3.24/100 patient-years. The distribution of HZ lesions was: head and neck region (15%), lower limbs (27%), trunk (55%) and upper limbs (4%). Fourteen episodes of HZ (25%) were treated by intravenous anti-viral drugs while others were treated at out-patient settings with oral acyclovir. Secondary bacterial infection occurred in 9% of the episodes. Disseminated disease or mortality was not reported in any patients. Significant post-herpetic neuralgia developed in 9% of the episodes. Patients with HZ reactivation were more likely to have first-time renal disease (76% vs 58%; p=0.02) and a shorter SLE duration at LN (31.4±50 vs 62.7±72 months; p=0.02) than those without HZ. A trend of higher SLEDAI score, higher anti-dsDNA titer, lower C3 and albumin level but higher rate of refractory renal disease was also observed in HZ-infected patients. Other clinical parameters such as histological classes of LN, neutrophil, lymphocyte counts and immunoglobulin levels at baseline and 6 months post-therapy were not significantly different between HZ-infected and control patients. HZ-infected patients had been treated with a significantly higher dose of prednisolone (0.72±0.40 vs 0.63±0.24 mg/kg/day) as induction therapy. Dosages of other immunosuppressive drugs were not associated with HZ reactivation. Logistic regression revealed first-time renal disease (OR 2.25[1.08-4.71]; p=0.003), peak MMF daily dose (OR 1.24[1.10-3.07]; p=0.02) and cumulative CYC dose (OR 1.14[1.01-1.28]; p=0.04) during induction therapy were significantly associated with HZ within 2 years.Conclusion:HZ reactivation is fairly common in LN patients undergoing immunosuppressive therapies but unpredictable from histological and laboratory parameters. Higher doses of prednisolone, MMF and CYC were associated with a higher risk of HZ reactivation within 2 years.Acknowledgments:NILDisclosure of Interests:None declared

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

The Preschool Stuttering Screen for Health Care Professionals

2011 ◽  
Vol 21 (2) ◽  
pp. 59-62
Author(s):  
Joseph Donaher ◽  
Christina Deery ◽  
Sarah Vogel
Keyword(s):  
Risk Factors ◽  
Health Care ◽  
Differential Diagnosis ◽  
Preschool Children ◽  
Health Care Professionals ◽  
Healthcare Professionals ◽  
Evidence Based ◽  
Developmental Profile

Healthcare professionals require a thorough understanding of stuttering since they frequently play an important role in the identification and differential diagnosis of stuttering for preschool children. This paper introduces The Preschool Stuttering Screen for Healthcare Professionals (PSSHP) which highlights risk factors identified in the literature as being associated with persistent stuttering. By integrating the results of the checklist with a child’s developmental profile, healthcare professionals can make better-informed, evidence-based decisions for their patients.

Clinical Response to Questions Regarding Outcomes and Therapy Efficacy

2010 ◽  
Vol 20 (3) ◽  
pp. 76-83 ◽  
Author(s):  
Joseph Donaher ◽  
Tom Gurrister ◽  
Irving Wollman ◽  
Tim Mackesey ◽  
Michelle L. Burnett
Keyword(s):  
Risk Factors ◽  
Clinical Response ◽  
Speech Language Pathologists ◽  
Specific Therapy ◽  
Therapy Efficacy ◽  
Therapy Program ◽  
Adults Who Stutter ◽  
Cure Rates

Parents of children who stutter and adults who stutter frequently ask speech-language pathologists to predict whether or not therapy will work. Even though research has explored risk-factors related to persistent stuttering, there remains no way to determine how an individual will react to a specific therapy program. This paper presents various clinicians’answers to the question, “What do you tell parents or adults who stutter when they ask about cure rates, outcomes, and therapy efficacy?”

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