Pneumonitis als gravierende Nebenwirkung bei Asthmapatienten unter Immuntherapie

2020 ◽  
Vol 8 (4) ◽  
pp. 204-205
Author(s):  
Susanne M. Lang
Keyword(s):  
Medical Records ◽  
Checkpoint Inhibitors ◽  
Cancer Center ◽  
Increased Risk ◽  
Characteristic Imaging ◽  
Life Threatening ◽  
History Of ◽  
Former Smokers ◽  
The Common ◽  
Grade 3

Introduction: Predicting the factors that increase the risk of immune-related pneumonitis, a potentially life-threatening complication of treatment with immune checkpoint inhibitors for cancer, is a clinical challenge. Baseline clinical factors such as asthma may portend the development of pneumonitis due to pre-existing airway inflammation prior to immunotherapy. Objective: The purpose of the study was to investigate whether a prior diagnosis of asthma is associated with an increased risk of immune-related pneumonitis in patients undergoing cancer immunotherapy. Methods: Patients at the Moores Cancer Center at UC San Diego Health undergoing immunotherapy were identified on an IRB-approved protocol. Clinical charts were reviewed for asthma documented in the medical records and CT scans were reviewed during and after treatment. Pneumonitis was defined as the onset of new pulmonary symptoms with characteristic imaging findings during or after a patient’s first course of immunotherapy that could not be readily explained as infection or a progression of malignancy. It was graded according to the Common Terminology Criteria for Adverse Events. Results: A total of 187 patients were included. A diagnosis of asthma was found in the records of 26 cases (13.9%). Pneumonitis was found in 10 cases (5.35%); 50% were grade 2 and 50% were grade 3–4. Two of the grade 3–4 cases (40%) occurred in patients with non-small-cell lung cancer. Three patients with asthma developed pneumonitis (11.5% of patients with asthma), all grade 3–4. Only 28.6% of the non-asthma-pneumonitis cases were grade 3–4. All (100%) of the asthma-pneumonitis patients were former smokers, while 71.4% of the non-asthma-pneumonitis patients were former smokers. Conclusion: A history of asthma may be associated with a higher grade of pneumonitis if it develops, and a history of smoking may augment this relationship.

scholarly journals PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  
Keyword(s):  
Health Science ◽  
Cancer Center ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Science Center ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

Does the primary tumour location affect the prognosis of patients with colorectal cancer peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haipeng Chen ◽  
Sicheng Zhou ◽  
Jianjun Bi ◽  
Qiang Feng ◽  
Zheng Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Primary Tumour ◽  
Cancer Center ◽  
Tumour Location ◽  
Life Threatening ◽  
Grade 3 ◽  
The Impact

Abstract Background The impact of primary tumour location on the prognosis of patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rarely discussed, and the evidence is still limited. Methods Patients with PM arising from CRC treated with CRS and HIPEC at the China National Cancer Center and Huanxing Cancer Hospital between June 2017 and June 2019 were systematically reviewed. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analysed. Results A total of 70 patients were divided into two groups according to either colonic or rectal origin (18 patients in the rectum group and 52 patients in the colon group). Patients with PM of a colonic origin were more likely to develop grade 3–4 postoperative complications after CRS+HIPEC (38.9% vs 19.2%, P = 0.094), but this difference was not statistically significant. Patients with colon cancer had a longer median overall survival (OS) than patients with rectal cancer (27.0 vs 15.0 months, P = 0.011). In the multivariate analysis, the independent prognostic factors of reduced OS were a rectal origin (HR 2.15, 95% CI 1.15–4.93, P = 0.035) and incomplete cytoreduction (HR 1.99, 95% CI 1.06–4.17, P = 0.047). Conclusion CRS is a complex and potentially life-threatening procedure, and we suggest that the indications for CRS+HIPEC in patients with PM of rectal origin be more restrictive and that clinicians approach these cases with caution.

scholarly journals Long-Lasting Increased Risk of Human Papillomavirus–Related Carcinomas and Premalignancies After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study

2017 ◽  
Vol 35 (22) ◽  
pp. 2542-2550 ◽  
Author(s):  
Renée M.F. Ebisch ◽  
Dominiek W.E. Rutten ◽  
Joanna IntHout ◽  
Willem J.G. Melchers ◽  
Leon F.A.G. Massuger ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Incidence Rate ◽  
Intraepithelial Neoplasia ◽  
Population Based ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Increased Risk ◽  
History Of ◽  
Grade 3 ◽  
Rate Ratios

Purpose The aim of this study was to determine the risk of human papillomavirus (HPV)–related carcinomas and premalignancies in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3). Knowledge of this risk is important to preventing the development and progression of other HPV-related premalignancies and carcinomas, by considering prophylactic HPV vaccination and/or by paying increased attention to other HPV-related carcinomas and premalignancies when CIN3 is identified. Methods Women diagnosed with a CIN3 between 1990 and 2010 were identified from the Dutch nationwide registry of histopathology and cytopathology (PALGA) and matched with a control group of women without CIN3. Subsequently, all cases of high-risk (hr) HPV–associated high-grade lesions and carcinomas in the anogenital region and oropharynx between 1990 and 2015 were extracted. Incidence rate ratios were estimated for carcinomas and premalignancies of the vulva, vagina, anus, and oropharynx. Results A total of 178,036 women were identified: 89,018 with a previous diagnosis of CIN3 and 89,018 matched control subjects without a history of CIN3. Women with a history of CIN3 showed increased risk of HPV-related carcinomas and premalignancies, with incidence rate ratios of 3.85 (95% CI, 2.32 to 6.37) for anal cancer, 6.68 (95% CI, 3.64 to 12.25) for anal intraepithelial neoplasia grade 3, 4.97 (95% CI, 3.26 to 7.57) for vulvar cancer, 13.66 (93% CI, 9.69 to 19.25) for vulvar intraepithelial neoplasia grade 3, 86.08 (95% CI, 11.98 to 618.08) for vaginal cancer, 25.65 (95% CI, 10.50 to 62.69) for vaginal intraepithelial neoplasia grade 3, and 5.51 (95% CI, 1.22 to 24.84) for oropharyngeal cancer. This risk remained significantly increased, even after long-term follow-up of up to 20 years. Conclusion This population-based study shows a long-lasting increased risk for HPV-related carcinomas and premalignancies of the anogenital and oropharyngeal region after a CIN3 diagnosis. Studies that investigate methods to prevent this increased risk in this group of patients, such as intensified screening or vaccination, are warranted.

scholarly journals Management of rheumatic complications of immune checkpoint inhibitor therapy – an oncological perspective

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_7) ◽  
pp. vii29-vii39 ◽  
Author(s):  
Neil M Steven ◽  
Benjamin A Fisher
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Cancer Control ◽  
Myasthenic Crisis ◽  
Life Threatening ◽  
Checkpoint Inhibitor Therapy ◽  
The Common ◽  
Risk And Benefit

Abstract Immune checkpoint inhibitors (CPIs) are an effective treatment for many cancers but cause diverse immune-related adverse events (IrAEs). Rheumatological IrAEs include arthralgia, arthritis, tenosynovitis, myositis, polymyalgia rheumatica and sicca syndrome. CPI use can unmask RA as well as causing flares of prior autoimmune or connective tissue disease. Oncologists categorize and grade IrAEs using the Common Terminology Criteria for Adverse Events and manage them according to international guidelines. However, rheumatological events are unfamiliar territory: oncologists need to work with rheumatologists to elicit and assess symptoms, signs, results of imaging and autoantibody testing and to determine the use of steroids and DMARDs. Myositis may overlap with myasthenic crisis and myocarditis and can be life-threatening. Treatment should be offered on balance of risk and benefit, including whether to continue CPI treatment and recognizing the uncertainty over whether glucocorticoids and DMARDs might compromise cancer control.

scholarly journals Incidence of and Risk Factors for Glenohumeral Osteoarthritis After Anterior Shoulder Instability: A US Population–Based Study With Average 15-Year Follow-up

2020 ◽  
Vol 8 (11) ◽  
pp. 232596712096251
Author(s):  
Bradley M. Kruckeberg ◽  
Devin P. Leland ◽  
Christopher D. Bernard ◽  
Aaron J. Krych ◽  
Diane L. Dahm ◽  
...  
Keyword(s):  
Risk Factors ◽  
Shoulder Instability ◽  
The United States ◽  
Anterior Shoulder Instability ◽  
Geographic Population ◽  
Increased Risk ◽  
Modifiable Factors ◽  
History Of ◽  
Former Smokers

Background: The rate of osteoarthritis (OA) in patients with a history of previous anterior shoulder instability (ASI) varies within the literature, with the majority of studies investigating rates after surgical stabilization. ASI appears to lead to increased rates of OA, although risk factors for developing OA in cohorts treated nonoperatively and operatively are not well-defined. Purpose: To determine the incidence of clinically symptomatic OA and identify potential risk factors for the development of OA in patients younger than 40 years with a known history of ASI. Study Design: Case-control study; Level of evidence, 3. Methods: An established, geographically based database was used to identify patients in the United States who were younger than 40 years and were diagnosed with ASI between 1994 and 2014. Patient information, including demographic, imaging, and surgical details, was collected. Comparative analysis was performed between groups with and without OA at final follow-up as well as between patients who underwent surgical and nonsurgical management. Results: The study population consisted of 154 patients with a mean follow-up of 15.2 years (range, 5.1-29.8 years). The mean age at initial instability event was 20.9 years (95% CI, 19.9-22.0 years). Overall, 22.7% of patients developed clinically symptomatic glenohumeral OA. Multivariate analysis revealed that current or former smokers (odds ratio [OR], 4.3; 95% CI, 1.1-16.5; P = .030), hyperlaxity (OR, 10.1; 95% CI, 1.4-72.4; P = .020), laborer occupation (OR, 6.1; 95% CI, 1.02-36.1; P = .043), body mass index (BMI) (OR, 1.2; 95% CI, 1.03-1.3; P = .012), and age at initial instability (OR, 1.1; 95% CI, 1.02-1.2; P = .013) as potential independent risk factors when accounting for other demographic and clinical variables. Conclusion: In a US geographic population of patients younger than 40 years with ASI, approximately one-fourth of patients developed symptomatic OA at a mean follow-up of 15 years from their first instability event. When accounting for differences in patient demographic and clinical data, we noted a potentially increased risk for the development of OA in patients who are current or former smokers, have hyperlaxity, are laborers, have higher BMI, and have increased age at initial instability event. Smoking status, occupation, and BMI are modifiable factors that could potentially decrease risk for the development of symptomatic OA in these patients.

Long-Term Health-Related Outcomes In Survivors Of Childhood Hematopoietic Cell Transplantation (HCT): A Report From The Bone Marrow Transplant Survivor Study (BMTSS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 553-553
Author(s):  
Saro Armenian ◽  
Can-Lan Sun ◽  
Mukta Arora ◽  
K. Scott Baker ◽  
Liton Francisco ◽  
...  
Keyword(s):  
Premature Death ◽  
Chronic Health Condition ◽  
Health Condition ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Chronic Health ◽  
Allogeneic Hct ◽  
Increased Risk ◽  
Life Threatening ◽  
Grade 3

Abstract Introduction HCT is frequently offered as a curative option for children with benign and malignant conditions. Improvement in HCT strategies have increased survival by approximately 10% per decade. Adult HCT survivors are at increased risk for chronic health conditions (Sun, Blood 2010), and premature death (Bhatia, Blood 2007; 2005). The magnitude of risk of these chronic health conditions and of premature death in childhood HCT survivors is not known. Methods Participants were drawn from the BMTSS, and included patients undergoing HCT between 1976 and 1998 at City of Hope or University of Minnesota. Participants were ≤21 years of age at HCT and were ≥2 yrs from myeloablative HCT. Participants completed a questionnaire addressing the diagnosis of physical health conditions (endocrinopathies, central nervous system compromise, cardiopulmonary dysfunction, gastrointestinal sequelae, musculoskeletal abnormalities, and subsequent malignancies), chronic GvHD (cGVHD), and sociodemographics. Chronic physical health conditions were graded using CTCAE v 3.0 (grade 1-5, ranging from mild to death due to chronic health condition). Relative risk (RR) regression was used to identify risk of health conditions and 95% confidence interval (CI). Information on vital status and cause of death was obtained from medical records, National Death Index, and Social Security Death Index, and compared with age-, sex-and calendar-specific mortality of the US general population (standardized mortality ratio [SMR]). Results The current study included 317 BMTSS participants. Median age at HCT was 7.9 yrs, and at study participation was 19.9 yrs; time from HCT was 10.3 yrs; 42% were female, 86.7% were non-Hispanic white, and 79% underwent allogeneic HCT. The most frequent indications for HCT included AML (27%), ALL (21%), SAA (13%), lymphoma (6%), and CML (5%). Total body irradiation (TBI) was used in 61% of 2 year survivors, and cGvHD was reported in 26%. Health Conditions: The cumulative incidence of a chronic health condition (grade 1-5) was 56% (95% CI: 51%-60%) at 15 years after HCT, with a cumulative incidence of 25% (95% CI: 20%-30%) for severe/life-threatening or fatal condition (grade 3-5, Figure). The highest incidence of grade 3-5 conditions was in allogeneic HCT recipients with cGvHD (32% at 15 years, 95% CI: 20%-44%; Figure). Risk Factors: After adjustment for age at HCT, follow-up, ethnicity/race, diagnosis, relapse risk at HCT, and treatment era, female participants were 1.2 (1.0-1.4, p=0.02) times more likely to report a chronic health condition, and 1.6 (1.1-2.4, p=0.01) times more likely to report a severe/life-threatening/fatal condition. Exposure to TBI was associated with a 1.3-fold (1.0-1.5, p=0.02) risk of a chronic health condition, and a 2.6-fold (1.4-4.91, p=0.003) risk of a severe/life-threatening/fatal condition compared to chemotherapy-only conditioning. Among allogeneic HCT recipients, cGvHD was associated with a 2.0-fold (1.2-3.2, p<0.01) risk of severe/life-threatening/fatal conditions when compared to survivors without cGvHD. Healthcare utilization: 92% of the survivors carried health insurance and 68% had been seen at their transplant center within the past 2 yrs. Late mortality: Overall survival in 2 year survivors was 80% at 10 years (68% autologous, 83% allogeneic, p<0.01). The primary cause of death included primary disease (61%), secondary cancer (8%), cGvHD (6%), cardiopulmonary compromise (5%), and other causes (21%). The cohort was at a 22-fold (SMR 22.0, 18.9-25.5, p<0.01) increased risk of premature death compared to age-and sex-matched general population. Female participants, those treated with TBI, and autologous HCT survivors had the highest risk of premature death (Table). Conclusions Childhood HCT survivors carry a substantial burden of morbidity, years following completion of therapy, providing clear evidence for their close monitoring in a specialized setting targeting these high risk complications. Disclosures: No relevant conflicts of interest to declare.

Gemcitabine-related thrombocytosis: Does it increase the risk of thrombosis?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6091-6091
Author(s):  
S. Ahmed ◽  
R. K. Shahid ◽  
A. Sami ◽  
S. Yadav ◽  
I. Ahmad ◽  
...  
Keyword(s):  
Platelet Count ◽  
Median Number ◽  
Vascular Event ◽  
Cancer Center ◽  
Platinum Compound ◽  
Advanced Malignancy ◽  
Exact Test ◽  
Patients With Cancer ◽  
Increased Risk ◽  
History Of

6091 Background: Gemcitabine is an antimetabolite agent that has demonstrated activity in various solid and hematological malignancies. Although thrombocytopenia is a known side effect, gemcitabine-related thrombocytosis has been uncommonly reported. Chemotherapy increases the risk of thrombo-embolism in patients with cancer. The study aimed to identify the incidence of gemcitabine-related thrombocytosis and to determine whether it has been associated with an increased risk of thrombo-embolism. Methods: Medical records of 175 consecutive adults patients with a malignant disease who received gemcitabine at Saskatoon Cancer Center were reviewed. Patients with history of prior thrombo-embolism or with baseline thrombocytosis were excluded. Fisher’s Exact test was done for statistical analysis. Results: 149 eligible patients with median age of 62 (26–83) and M:F of 1.01:1 were identified. 141 (95%) patients had advanced malignancy and 61 (41%) had received prior chemotherapy. 106 (71%) patients received combination of chemotherapy and 95% of those patients received gemcitabine in combination with a platinum compound. Median number of cycle was 3 (1–8). Median platelets count prior to commencement of gemcitabine was 285 × 109 (44–449). 83 (56%) patients experienced thrombocytopenia whereas 69 (46%) patients experienced thrombocytosis within 3 weeks of treatment with gemcitabine. Median post-gemcitabine platelet count in patients with thrombocytosis was 622 × 109 (457–1385). 15 (10%) patients experienced thrombocytosis with each cycle of gemcitabine. Median duration of thrombocytosis was 2 weeks (0.5−5). 13 (9%) of 149 patients experienced a vascular event (venous, n=9; arterial, n=4) within 6 weeks of treatment with gemcitabine. Median platelet count prior to the vascular event was 268 × 109 (79–669). All except one patient had advanced malignancy and 85% had received combination of chemotherapy. 5 of 69 (7%) patients with thrombocytosis experienced a vascular event compared with 8 of 80 (10%) patients without thrombocytosis (p=0.77). Conclusions: Gemcitabine has been associated with an increased incidence of thrombocytosis. However gemcitabine-related thrombocytosis is a transient phenomenon and has not been associated with an increased risk of a vascular event. No significant financial relationships to disclose.

Cetuximab use without chronic antihistamine premedication

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13521-13521 ◽  
Author(s):  
J. Timoney ◽  
K. Y. Chung ◽  
V. Park ◽  
R. Trocola ◽  
C. Peake ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Center ◽  
First Year ◽  
Institutional Practice ◽  
Chemotherapy Administration ◽  
Time Period ◽  
Life Threatening ◽  
Anaphylactoid Reactions ◽  
Grade 3 ◽  
Severe Grade

13521 Background: Cetuximab is a human-murine chimeric monoclonal antibody against EGFR with approximately a 3% reported incidence of severe (≥ grade 3) anaphylactoid reactions. The overwhelming majority of such reactions have been reported with the initial dose of cetuximab. Diphenhydramine (Benedryl)or a related antihistamine is often given as a premedication for cetuximab, however this may cause fatigue or other side effects. Most early clinical trials of cetuximab permitted investigator discretion in use of premedication beyond the initial cetuximab dose. Methods: We obtained an IRB waiver of authorization to review the records of patients treated with cetuximab at Memorial Sloan Kettering Cancer Center for the first year of commercial availability of cetuximb (Feb, 2004 through Feb, 2005). Computerized pharmacy records were reviewed to identify all patients who were treated with cetuximab (outside of a clinical trial) and use of premedication was then evaluated. Records of institutional adverse event reports regarding chemotherapy administration were reviewed, and, any moderate or severe/life-threatening reactions were evaluated for presence or absence of concurrent premedication. Results: As per our institutional guidelines, all patients received 50 mg of diphenhydramine prior to the initial loading dose of cetuximab, and 25 mg of diphenhydramine prior to the second dose. While there was inconsistency in terms of cessation of diphenhydramine, overall a total of 115 patients received one or more doses of cetuximab without premedication. A total of 746 doses of cetuxmab without diphenhydramine premedication were given over this time period. No severe/life-threatening reactions to cetuximab occurred during these doses given without premedication. Conclusions: Omission of diphenhydramine premedication after the initial two doses of cetuximab is our current institutional practice, and appears not to alter the safety profile of cetuximab. Considering the side effects of diphenhydramine, routine long tern use of antihistamine premedication with cetuximab administration does not appear to be warranted. [Table: see text]

Examining ethnic differences for bevacizumab-induced hypertension and proteinuria

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21168-21168 ◽  
Author(s):  
Y. M. Choi ◽  
S. Shord ◽  
S. Cuellar ◽  
J. Villano
Keyword(s):  
Clinical Benefit ◽  
Previous History ◽  
Retrospective Chart Review ◽  
Increased Risk ◽  
High Prevalence ◽  
Induced Hypertension ◽  
History Of ◽  
Grade 3 ◽  
The University ◽  
Ethnic Variations

21168 Background: Bevacizumab is an increasingly used anti-cancer treatment with common side effects including hypertension (htn) and proteinuria which occur in approximately 10% and 20% of the patients, respectively. Little is known regarding ethnic variations of bevacizumab induced htn and proteinuria, particularly in African-Americans (AA) who have a high prevalence of htn and susceptibility to kidney disease. Methods: We conducted a retrospective chart review of patients who completed bevacizumab alone or as a chemotherapy regimen at the University of Illinois at Chicago for an 18-month study period. We collected blood pressure (BP) measurements and urinanalyses before starting bevacizumab, during bevacizumab and after stopping bevacizumab, in addition to concurrent medications, past medical history and demographics. Htn and proteinuria were graded by CTC v3.0. Patients with less than two successive doses of bevacizumab or unreliable ethnicity were excluded. Results: 27 subjects were eligible. Eighteen AA (67%) and 9 (33%) non-AA were included. Twenty-two (81%) had colorectal cancer. AA received a median of 10 cycles and non-AA received a median of 6 cycles. Six subjects (22%) developed any grade htn toxicity; maximum grade: grade 2=4 (15%), grade 3=2 (7%). Htn toxicity occurred in 28% AA and 11% non-AA (p=NS). Previous history of hypertension was found in 15 subjects (55%): AA=14 vs. non-AA=1 (p=0.002) and was not correlated with hypertensive toxicity. Twelve subjects (44%) developed any grade proteinuria; maximum grade: grade 1=9 (33%), grade 2=3 (11%). Proteinuria toxicity occurred in 50% AA and 33% non-AA (p=NS). Presence of hypertensive toxicity was associated with increased risk of proteinuria. Clinical benefit (PR, SD) was seen in 15 subjects (55%). Rate of clinical benefit was 67% in AA and 33% in non-AA (p=NS). Clinical benefit did not correlate with hypertensive or proteinuria toxicities. Conclusions: AA were more prone than non-AA to bevacizumab induced hypertension and proteinuria toxicity in this retrospective study. Higher clinical benefit was seen in AA. No significant financial relationships to disclose.

Long term morbidity and mortality among survivors of infant neuroblastoma: A report from the Childhood Cancer Survivor Study (CCSS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10051-10051
Author(s):  
Danielle Novetsky Friedman ◽  
Pamela J Goodman ◽  
Wendy Leisenring ◽  
Lisa Diller ◽  
Susan Lerner Cohn ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Malignant Neoplasms ◽  
Cumulative Mortality ◽  
Late Mortality ◽  
Increased Risk ◽  
Life Threatening ◽  
Standardized Mortality Ratios ◽  
Grade 3 ◽  
The Impact

10051 Background: Infants with neuroblastoma typically have low-risk disease with excellent survival. Therapy has been de-intensified over time to minimize late effects, however the impact on survivors’ risk of late mortality, subsequent malignant neoplasms (SMN), and chronic health conditions (CHC) is unclear. Methods: We evaluated late mortality, SMNs and CHCs (graded according to CTCAE v4.03), overall and by diagnosis era, among 990 5-year neuroblastoma survivors diagnosed at < 1 year of age between 1970-1999. Cumulative mortality, standardized mortality ratios (SMR), and standardized incidence ratios (SIR) of SMNs were estimated using the National Death Index and SEER rates, respectively. Cox proportional hazards estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC, compared to 5,051 CCSS siblings. Results: Among survivors (48% female; median attained age: 24 years, range 6-46), there was increased treatment with surgery alone across the 1970s, 1980s and 1990s (21.5%, 35.3%, 41.1%, respectively), but decreased treatment with combination surgery + radiation (22.5%, 5.3%, 0.3%, respectively) and surgery + radiation + chemotherapy (28.7%, 14.7%, 9.3%, respectively). The 20-year cumulative mortality was 2.3% (95% CI, 1.4-3.8), primarily due to SMNs (SMRSMN= 10.0, 95% CI, 4.5-22.3). The 20-year cumulative incidence of SMN was 1.2% (95% CI, 0.3-3.2), 2.5% (95% CI, 1.3-4.4), and zero for those diagnosed in the 1970s, 1980s, and 1990s, respectively. SIR was highest for renal SMNs (SIR 12.5, 95% CI, 1.7-89.4). Compared to siblings, survivors were at increased risk for grade 1-5 CHC (HR 2.1, 95% CI, 1.9-2.3) with similar HR across eras (HR1970s= 1.9, 95% CI, 1.6-2.2; HR1980s= 2.2, 95% CI, 1.9-2.6; HR1990s= 2.0, 95% CI, 1.7-2.4). The HR of severe, disabling, life-threatening and fatal CHC (grades 3-5) decreased in more recent eras (HR1970s= 4.7, 95% CI, 3.4-6.6; HR1980s= 4.4, 95% CI, 3.2-6.2; HR1990s= 2.9, 95% CI, 2.0-4.3). Conclusions: Survivors of infant neuroblastoma remain at increased risk for late mortality, SMN, and CHCs many years after diagnosis. However, the risk of grade 3-5 CHCs has declined in more recent eras, likely reflecting de-intensification of therapy.

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