scholarly journals Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non–Small-Cell Lung Cancer

2017 ◽  
Vol 35 (13) ◽  
pp. 1395-1402 ◽  
Author(s):  
Robert T. Dess ◽  
Yilun Sun ◽  
Martha M. Matuszak ◽  
Grace Sun ◽  
Payal D. Soni ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Cardiac Disease ◽  
Cardiac Event ◽  
Locally Advanced ◽  
Cardiac Events ◽  
Eligibility Criteria ◽  
Heart Dose ◽  
Grade 3 ◽  
Mean Heart Dose

Purpose Radiation therapy is a critical component in the care of patients with non–small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had pre-existing cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.

An update on the dosimetric analysis of concurrent radiation therapy and trastuzumab on early cardiac events.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 121-121
Author(s):  
K. S. Keene ◽  
L. C. Klepczyk ◽  
R. Meredith ◽  
A. Forero-Torres ◽  
J. T. Carpenter ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Heart Disease ◽  
Breath Hold ◽  
Cardiac Events ◽  
Cardiac Morbidity ◽  
Heart Dose ◽  
Dosimetric Analysis ◽  
Mean Heart Dose ◽  
The Impact

121 Background: The impact of radiation therapy (RT) with concurrent trastuzumab on early cardiac morbidity is relatively unknown. Trastuzumab’s radiosensitizing properties may augment both early and late effects of RT. This retrospective review update provides an analysis of cardiac event (CE) development in patients treated with concurrent RT and trastuzumab with a focus on RT heart dose. Methods: Sixty-five patients treated with concurrent RT (30 left, 33 right, 2 bilateral) and trastuzumab at the University of Alabama at Birmingham were identified. Patient data for pre-existing heart disease, cardiac risk factors, drug regimen, and CEs were recorded. Dosimetric parameters of maximum heart dose, mean heart dose, heart volume receiving 5, 10, 15, 20 and 30Gy (V5, V10, V15, V20, V30) were also analyzed. Endpoints include the occurrence of CEs at any time in relation to RT and those specifically after the start of RT. Results: In addition to receiving trastuzumab, 80% of patients received doxorubicin. 15.4% had preexisting heart disease. The mean heart dose for all patients was 248cGy. With a median follow-up of 24.5 months, six patients developed CEs (9.2%), and three of these cases occurred after RT initiation (4, 4, and 0.5 months post-RT). All six CEs occurred during treatment with trastuzumab and consisted of congestive heart failure. Analysis of the heart dose maximum, mean, V5, V10, V15, and V20, V30 were similar in patients with and without CEs, and small differences between groups did not reach statistical significance. CE incidence was significantly associated with smoking (p=0.0037) but not hypertension, diabetes or pre-existing heart disease. Conclusions: This updated retrospective dosimetric analysis did not find a correlation between concurrent trastuzumab and RT on the development of early cardiac events. Modern era RT with 3D conformal planning, the use of heart blocks, and breath hold techniques will continue to decrease the dose to the heart. Longer follow-up will be needed for analysis of the impact of modern technologic advances and late cardiac morbidity.

Ischemic Cardiac Event

2019 ◽  
Author(s):  
Megan Lanigan ◽  
Matthew Culling ◽  
Robert Gould ◽  
Michael Wall ◽  
Joss Thomas
Keyword(s):  
Cardiac Surgery ◽  
Cardiac Disease ◽  
Cardiac Event ◽  
Myocardial Injury ◽  
High Cholesterol ◽  
Cardiac Events ◽  
Troponin Elevation ◽  
Adverse Cardiac Events ◽  
Common Causes ◽  
Artery Disease

An estimated 92.1 million Americans have at least one type of cardiovascular disease (CAD).1  Even though death rates due to CAD have declined, at least 2200 Americans die each day of CAD. 2 In the U.S. at least 50 million operations occur every year and up to 4% are associated with adverse cardiac events. 3There are many identifiable risk factors for cardiac disease such as diabetes, hypertension, obesity, smoking, and high cholesterol. 1In addition, there are non-modifiable risks for cardiac disease; these include age, gender, family history, and homocysteine levels. 4 Hypotension and tachycardia are the most common causes of ischemic cardiac events in the intra-operative phase. The failure to detect myocardial injury early on may contribute to complications as long as 30 days post-operatively. Typically, ischemic findings on electrocardiography and elevated troponin measurements have been used as potential indicators of ischemia or myocardial injury after non-cardiac surgery in the peri-operative setting. In the treatment of ischemic cardiac events, intensified medical therapy (antiplatelet, beta-blocker, ACE inhibitor, or a statin) in patients who suffered from a troponin elevation in the postoperative period reduces the risk of having a major cardiac event within a year.  This review contains 1 figure, 2 tables, and 74 references.  Keywords: Myocardial Injury after Non Cardiac Surgery (MINS), Perioperative ischemia, Troponin assay, VISION study, Coronary artery disease

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma

2018 ◽  
Vol 36 (19) ◽  
pp. 1913-1921 ◽  
Author(s):  
Pierce K.H. Chow ◽  
Mihir Gandhi ◽  
Say-Beng Tan ◽  
Maung Win Khin ◽  
Ariunaa Khasbazar ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Locally Advanced ◽  
Asia Pacific ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Advanced Hcc ◽  
Selective Internal Radiation ◽  
Internal Radiation Therapy ◽  
Sorafenib Group ◽  
Grade 3

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Phase I trial of chemotherapy combination with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/ metastatic head and neck cancer (HNC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6064-6064
Author(s):  
M. Tahara ◽  
K. Araki ◽  
N. Kiyota ◽  
S. Takeuchi ◽  
N. Fuse ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Response Rate ◽  
Locally Advanced ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Eligibility Criteria ◽  
Adequate Organ Function ◽  
Grade 3

6064 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC) with a response rate of 34% and preclinical data has demonstrated a possible synergy with platinums and taxanes. The aim of this study was to determine the maximum tolerated dose (MTD) of a combination therapy with TPS in patients (pts) with locally advanced or recurrent/ metastatic HNC. Methods: The eligibility criteria were: histologically proven squamous cell carcinoma of the head and neck with recurrent/metastatic and locally advanced lesions, PS 0–1, age =75 years, adequate organ function, and no prior chemotherapy. Chemotherapy consisted of 1-hour infusion of docetaxel at escalating doses of 50 and 60 mg/m2, 2-hour infusions of cisplatin at 70 mg/m2/day on day 1 and S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day. The treatment was repeated every 4-weeks. Results: Twenty two pts were enrolled. These were 17 males and 5 females with a median age of 50 years (22–74). There were 11 locally advanced and 11 metastatic cases. Median of 3 cycles were administrated (range 1–6; total 77 cycles). Anorexia, nausea, neutropenia and anemia were the most frequently observed adverse events. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (0%), anemia (14%) and thrombocytopenia (0%). Although a total of 12 pts were treated with TPS at doses of 60/70/80 mg/m2/day, one-dose limiting toxicity (grade3 infection) was observed at these doses, but MTD was not reached. As the approved dose of S-1 is 80 mg/m2, further dose escalation was not conducted. In a total of 22 pts treated with the TPS, 3 (1 locally advanced, 2 metastatic cases) achieved complete response and 11 (7 locally advanced, 4 metastatic cases) achieved partial response according to RECIST with an overall response rate of 64%. Conclusions: The TPS combination was well tolerated in pts with locally advanced or recurrent/ metastatic HNC. Although MTD was not reached and the data were preliminary, the antitumor activity was very promising, and this warrants further investigation. No significant financial relationships to disclose.

Final results of a phase I trial of chemotherapy combination with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent metastatic head and neck cancer (HNC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6021-6021
Author(s):  
M. Tahara ◽  
K. Araki ◽  
N. Kiyota ◽  
S. Okano ◽  
N. Fuse ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Dose Level ◽  
Neck Cancer ◽  
Response Rate ◽  
Metastatic Cancer ◽  
Locally Advanced ◽  
Maximum Tolerated Dose ◽  
Eligibility Criteria ◽  
Grade 3

6021 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC), with a response rate of 34%. We investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin and S-1 (TPS) in patients (pts) with locally advanced or recurrent/metastatic HNC. Methods: Eligibility criteria were histologically proven HNC, PS 0–1, age ≤75 years, adequate organ function, and no prior chemotherapy. Treatment consisted of 1-hour infusion of docetaxel at escalating doses of 50, 60 and 70 mg/m2, 2-hour infusion of cisplatin at 70 mg/m2/day on day 1, and S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day. This regimen was repeated every 3 or 4 weeks. Pts with locally advanced HNC received concurrent chemoradiotherapy after completion of 3 cycles of TPS. Results: Forty pts were enrolled, consisting of 33 males and 7 females with a median age of 50 years (range 22–74 years). Twenty-nine cases were locally advanced cancer and 11 were metastatic cancer. 116 cycles (median = 3, range 1–6) were administered in 6 dose levels. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (13%), and anemia (8%), whereas no grade 3 or 4 thrombocytopenia was seen. Two dose-limiting toxicities (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg/m2/day every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 pts treated at dose level 6 (TPS: 70/70/60 mg/m2/day every 3 weeks), three DLTs were seen, namely one grade 3 diarrhea, one grade 3 ALT/AST and one grade 2 creatinine elevation. Of a total of 40 pts, 6 achieved a complete response and 22 a partial response according to RECIST, giving an overall response rate of 70%. Conclusions: The TPS combination was well tolerated. The recommended phase II dose was determined to be TPS at 70/70/60 mg/m2/day every 3 weeks. Antitumor activity was highly promising, and warrants further investigation. No significant financial relationships to disclose.

Survival and toxicity with intensity modulated radiation therapy (IMRT) and chemotherapy for esophageal carcinoma, with or without surgery.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 125-125
Author(s):  
Kristin Kowalchik ◽  
Elizabeth Johnson ◽  
George P. Kim ◽  
C. Daniel Smith ◽  
Siyong Kim ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Acute Toxicity ◽  
Esophageal Carcinoma ◽  
Locally Advanced ◽  
Late Toxicity ◽  
Concurrent Chemotherapy ◽  
Conformal Radiation Therapy ◽  
Trimodality Therapy ◽  
Grade 3 ◽  
3D Crt

125 Background: Treatment for locally advanced esophageal carcinoma is radiation and chemotherapy, with or without surgery. Radiation has traditionally been delivered with 3D conformal radiation therapy (3D CRT). This study evaluates late toxicity in patients treated with IMRT as well as early outcomes and acute toxicity. Methods: This is a retrospective review of 32 patients with esophageal carcinoma treated with IMRT at Mayo Clinic Florida from 2008 -2012. Pathology includes squamous cell and adenocarcinomas. Tumor sites include middle and lower thoracic and GE junction. Clinical stages are TX-T3, N0-3, M0-1. All patients received at least one cycle of concurrent chemotherapy. IMRT dose was 50.4 Gy in 28 fractions prescribed to a target volume including the tumor and regional lymphatics. IMRT plans utilized coplaner beams in a 7-9 beam arrangement or volumetric modulated arc therapy. Results: Median follow-up is 8.9 months (range 2.4-23.0) for all patients and 13.1 months (range 2.8-23.0 months) in surviving patients. Median patient age is 69 (range 46-87). Trimodality treatment was completed in 20 patients (62.5%). Surgery was either an open or minimally invasive esophagogastrectomy. The incidence of grade 3 or greater late toxicity at 1 year was 48% in surgery patients and 26% in non-surgery patients. The most common grade 3 or higher toxicity was esophageal strictures in 25%. The incidence of any grade 3 or greater acute toxicity was 65% in the surgery patients and 75% in the non-surgery patients. Overall survival (OS) for all patients at 18 months is 57% (CI 37-86%) and progression-free survival (PFS) is 60% (36-99%). OS and PFS for trimodality therapy at 12 months is 83% (66-100%) and 81% (63-100%) respectively and for bimodality therapy is 34% (12-93%) and 70% (33-100%) respectively. Conclusions: Increased late toxicity occurs in surgery patients, and increased acute toxicity in non-surgery patients. Lower survival in non-surgery patients may be due to early progression, morbidities which preclude surgery or improved survival with surgery. Overall, IMRT is a feasible treatment modality, which may be equally efficacious to 3D CRT for the treatment of esophageal carcinoma.

FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Lipika Goyal ◽  
Funda Meric-Bernstam ◽  
Antoine Hollebecque ◽  
Juan W. Valle ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Disease Progression ◽  
Intrahepatic Cholangiocarcinoma ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Gene Fusions ◽  
Phase 2 ◽  
Fgfr2 Gene ◽  
Platinum Based Chemotherapy ◽  
Grade 3

108 Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 ( FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ≥1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ≥6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ≥3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ≥3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ≥3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information: NCT02052778.

scholarly journals Dose Volume Relationship in Estimating Cardiac Doses in Breast Cancer Radiotherapy

2020 ◽  
Author(s):  
Lucy Pattanayak ◽  
Swodeep Mohanty ◽  
Deepak Kumar Sahu ◽  
Tapas Kumar Dash ◽  
Itishree Priyadarsini
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Conformal Radiotherapy ◽  
Free Breathing ◽  
P Value ◽  
Carcinoma Breast ◽  
Heart Dose ◽  
Cardiac Dose ◽  
The Mean ◽  
Mean Heart Dose

Introduction: Radiation therapy is an integral part of adjuvant treatment for breast cancer which reduces local recurrence and significantly increases survival. But, radiation therapy also has the propensity to increase cardiac morbidity and mortality due to dose received by the heart which is more in left-sided breast cancer. Mean Heart dose and Maximum Heart Distance (MHD) are two parameters to study dose received by the heart. Aim: The purpose of this study was to determine individual doses received by the heart and to correlate MHD with the mean heart dose received by heart in carcinoma breast patients receiving radiotherapy. Materials and Methods: Ninety patients of histologically proven carcinoma breast who attended the Department of Radiotherapy, Acharya Harihar Regional Cancer, Cuttack from January 2017 to January 2019 were selected for a prospective observational study. All patients were treated with 3D Conformal Radiotherapy technique using free breathing multi slice Computed Tomography (CT) scans to contour target and vital organs. Parallel opposed tangential treatment plans were generated for each patient. Individual dose received by the heart and MHD was assessed for each case. SPSS version 21 used for statistical analysis. The Spearman’s Rho test was used for correlation of MHD with Mean heart dose. The Mann-Whitney U test was used for comparing mean of MHD in left-sided and right-sided breast cancer. The Independent t-test was used for comparing means of Mean heart dose in left-sided and right-sided breast cancer. A p-value <0.05 was considered as statistically significant. Results: The Mean Heart Dose was 4.63 Gy for left-sided breast carcinoma patients and 0.846 Gy for right-sided breast cancer and there was a significant difference (p<0.001). Mean MHD for left-sided breast cancer was 2.974 cm while for right-sided it was 0.017 cm, the difference was statistically significant (p-value <0.001). MHD also correlated positively with Mean Heart Dose with correlation coefficient of 0.849 and p-value <0.001. Conclusion: MHD and Mean Heart dose were significantly higher in left-sided breast cancer receiving radiotherapy. MHD was also found to be positively related to Mean Heart dose and therefore found to be an important predictor of cardiac dose. For right-sided breast carcinoma receiving radiotherapy, free breathing technique using 3-Dimensional Conformal Radiotherapy (3DCRT) will suffice in terms of cardiac dose.

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