Prior Mediastinal Radiation Research Articles

Abstract 4144542: In-Hospital Outcomes of Open Mitral Valve Repair or Replacement versus Percutaneous Mitral Valve Repair or Replacement in patients with Prior Mediastinal Radiation: Insight from The National Inpatient Database (2015-2020)

Background: Radiation associated heart disease has a wide spectrum of manifestations including pericardial disease, coronary artery disease, and valvular heart disease. Mitral valve regurgitation is the second most common valvular dysfunction in patients with prior mediastinal radiation. Research Question: What are the outcomes of percutaneous or transcatheter mitral valve replacement/repair (T-MVR) versus surgical mitral valve replacement/repair (S-MVR) in patients with prior mediastinal radiation. Methods: The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify patients with mediastinal tumors and prior exposure to radiation therapy undergoing mitral valve repair/replacement. We subclassified the data into hospitalizations for S-MVR and T-MVR. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes. Results: A total of 1725 patients with prior mediastinal radiation were hospitalized for MVR; 1110 (64.3%) patients underwent S-MVR and 615 (35.6%) patients underwent T-MVR. On a multivariable analysis, the odds of MACCE [aOR: 2.21; 95 % CI: (1.87-4.01); p <0.001)], and in-hospital mortality [aOR: 5.6; 95% CI (2.06-7.35); p=0.008] were higher in patients undergoing S-MVR compared to those undergoing T-MVR. Additionally, patients undergoing S-MVR had higher odds of periprocedural complications including cardiogenic shock [aOR: 7.4; 95% CI: (3.75 -9.20); p <0.001], major bleeding [aOR: 2.9; 95% CI: (1.26-7.09); p=0.01], AKI [aOR: 3.4; 95% CI: (1.33-5.23); p <0.001], stroke [aOR: 5.01; 95% CI: (1.51-6.57); p=0.008], and MCS utilization [aOR: 3.05; 95% CI: (1.31-7.13); p=0.009] compared to the T-MVR cohort. Conclusion: Compared to T-MVR, S-MVR was associated with higher odds of MACCE, in-hospital mortality and periprocedural complications suggesting that T-MVR might be a safer option for MVR among patients with prior mediastinal radiation.

Incidence and Risk Factors for Permanent Pacemaker Implantation After Tricuspid Valve Repair

BackgroundAlthough the likelihood of needing a permanent pacemaker (PPM) after tricuspid valve (TV) repair has been thought to be low compared with TV replacement, the incidence and determinants are controversial. This study aimed to evaluate the incidence and risk factors for PPM implantation after TV repair. MethodsA total of 1237 consecutive patients undergoing TV repair from 1997 to 2019 were reviewed using a prospectively maintained database, and 1058 patients were enrolled. ResultsIncidence of PPM implantation was 10.3% (n = 109). Median time to PPM implantation was 7 (range, 6-9) days. Indications for PPM implantation were heart block (n = 62, 56.9%), junctional or sinus bradycardia (n = 21, 19.3%), and ventricular arrhythmia (n = 17, 15.6%). Likelihood of PPM varied with concurrent procedures: left ventricular assist device (3.4%), mitral repair (11.2%), mitral valve replacement (13.7%), aortic and mitral valve replacement (19.2%), and isolated tricuspid repair (6.5%). Older age (odds ratio [OR], 1.020; 95% CI, 1.003-1.036), prior mediastinal radiation (OR, 4.106; 95% CI, 1.598-10.554), and concomitant mitral and aortic valve replacement (OR, 1.963; 95% CI, 1.046-3.683) were risk factors, and concomitant left ventricular assist device implantation (OR, 0.325; 95% CI, 0.139-0.759) was a protective factor for PPM implantation. PPM implantation did not affect the early outcomes, overall survival (P =.287), or cumulative incidence of recurrent moderate or greater tricuspid regurgitation (P =.890) or TV reoperation (P =.602). ConclusionsThe likelihood of PPM implantation after TV repair is relatively high, but PPM implantation does not affect the early and long-term clinical outcomes. Older age, prior mediastinal radiation, and concomitant mitral and aortic valve replacement are risk factors, and concomitant left ventricular assist device implantation is a protective factor for PPM implantation after TV repair.

Abstract 13389: Outcomes of Transcatheter Aortic Valve Replacement in Patients With Prior Mediastinal Radiation in the United States

Introduction: Although prior mediastinal radiation is associated with significantly worse clinical outcomes after SAVR, it is unknown if the same holds true for patients undergoing transcatheter aortic valve replacement (TAVR). Hypothesis: We hypothesized that the presence of prior mediastinal radiation may affect the outcomes of patients undergoing TAVR and tested this hypothesis using data from a nationally representative sample of the US population. Methods: The National Readmissions Database was analyzed from 2016-2019 to identify patients ≥ 18 years old undergoing TAVR. Patients with prior mediastinal radiation were then identified by using ICD-10 CM codes. Propensity score matching was used to adjust for confounders. Results: Our cohort included 173,743 patients undergoing TAVR, of which 2,780 (1.6%) had prior mediastinal radiation. Patients with prior mediastinal radiation undergoing TAVR were younger, had a higher proportion of females, and had a lower burden of comorbidities including hypertension, diabetes, and renal failure. Crude percentages are reported in Figure 1. On propensity score-matched analysis, the presence of prior mediastinal radiation was associated with similar odds of in-hospital mortality and peri-procedural complications including cardiovascular complications, peripheral vascular complications, pulmonary complications, neurological complications, major bleeding, and new pacemaker implantation along with similar odds of 30-day and 180-day all-cause, stroke-related, bleeding-related, and heart failure-related readmissions compared to those without prior mediastinal radiation. Conclusion: In conclusion, our data suggest that patients with prior mediastinal radiation undergoing TAVR have similar outcomes compared to those who have no history of mediastinal radiation.

Abstract 18970: Sex Differences and In-Hospital Outcomes of Acute Coronary Syndrome Among Patients With Mediastinal Radiation Exposure: Insights From the National Inpatient Sample (2009-2020)

Background There is a paucity of data about the sex disparities and temporal trends in outcomes of Acute Coronary Syndrome (ACS) patients with prior mediastinal radiation. Methods: The National Inpatient Sample database years 2009 to 2020 was queried for ACS hospitalizations of patients with prior mediastinal radiation. The primary outcome was MACCE (major cardiovascular events) and secondary outcomes included other hospital cardiovascular outcomes including hospital resource utilization. Results: A total 23385 hospitalizations for ACS with prior mediastinal radiation exposure were identified. Females accounted for 15904 (68.01%) of the cases. Median age was 70 vs 72 and the majority of the cases were whites 82.79% vs 78.22% for females and males respectively. Cases were mostly non-ST elevation MI in both genders 75.98% vs 79.71% while ST-elevation MI represented 24.02% vs 20.29% of them. Female patients with ACS had a higher burden of hypertension, diabetes mellitus, hyperlipidemia and obesity, however, males had a higher burden of Peripheral vascular disease, chronic heart failure and smoking. After propensity matching, primary outcome related to MACCE was higher in males (aOR1.803, 95%CI (1.65-1.96)) along with cardiogenic shock (aOR: 1.77, 95%CI (1.55-2.02)) and Mechanical Circulatory Support (MCS) use (aOR: 1.48, 95%CI (1.29 -1.71)). Similar findings were noted after the subgroup analysis in STEMI and NSTEMI where males had the worst In-hospital outcomes compared to females. Overall, we observed an increasing trend in ACS hospitalizations among females from 2.85% in 2009 to 7.91% in 2020 however, mortality decreased over the years from 8.69% in 2009 to 3.51% in 2020. Conclusions: This nationwide observational analysis showed significant disparities and burden of cardiovascular comorbidities among male and female ACS patients with prior mediastinal radiation history, with higher hospitalization rates among females but higher mortality among males.

Mediastinal radiation therapy for breast cancer in female patients is an independent risk factor for atrial fibrillation recurrence post-catheter ablation.

The aim of this study was to assess the safety, efficacy, and predictors of outcomes for atrial fibrillation (AF) ablation in patients with a history of breast cancer. Consecutive patients with a history of breast cancer undergoing AF ablation from January 2010 to December 2021 were propensity matched in a 1:1 ratio to patients without a history of any cancer. The primary outcome was procedural efficacy, defined by clinical AF recurrence and repeat catheter ablation. The secondary outcome was an assessment of safety looking at eight peri-procedural events. Our cohort was comprised of 82 female patients, 41 patients with a history of breast cancer (mean age, 74.6 ± 7.4years), and 41 patients with no history of cancer (76.7 ± 8.1years). Both groups had similar echocardiographic, baseline, and arrhythmia characteristics. Breast cancer patients were at an increased risk of AF recurrence post-ablation compared to non-cancer patients (OR 2.68, 95% CI 1.05-6.86, p = 0.04). Multivariate analysis found prior mediastinal radiotherapy (OR 4.79, 95% CI 1.34-17.1) and AF diagnosis to ablation time (OR 1.2, 95% CI 1.03-1.29) were both independent predictors of AF recurrence post-ablation. Our study suggests that female patients with a history of breast cancer are at a higher risk of developing AF recurrence after catheter ablation. Multivariate analysis showed that patients with a history of prior mediastinal radiation therapy and AF diagnosis to time to ablation were both independent risk factors.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With PriorMediastinal Radiation.

This study sought to evaluate the trends and outcomes of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) among patients with prior mediastinal radiation from a national database. There is a paucity of data about the temporal trends and outcomes of TAVR versus SAVR in patients with prior mediastinal radiation. The National Inpatient Sample database years 2012 to 2017 was queried for hospitalizations of patients with prior mediastinal radiation who underwent isolated AVR. Using multivariable analysis, the study compared the outcomes of TAVR versus SAVR. The main study outcome was in-hospital mortality. The final analysis included 3,675 hospitalizations for isolated AVR; of whom 2,170 (59.1%) underwent TAVR and 1,505 (40.9%) underwent isolated SAVR. TAVR was increasingly performed over time (ptrend=0.01), but there was no significant increase in the rates of utilization of SAVR. The following factors were independently associated with TAVR utilization: older age, chronic lung disease, coronary artery disease, chronic kidney disease, prior cerebrovascular accidents, prior coronary artery bypass grafting, and larger-sized hospitals, while women were less likely to undergo TAVR. Compared with SAVR, TAVR was associated with lower in-hospital mortality (1.2% vs. 2.0%, adjusted odds ratio: 0.27; 95% confidence interval: 0.09 to 0.79; p=0.02). TAVR was associated with lower rates of acute kidney injury, use of mechanical circulatory support, bleeding and respiratory complications, and shorter length of hospital stay. TAVR was associated with higher rates of pacemaker insertion. This nationwide observational analysis showed that TAVR is increasingly performed among patients with prior mediastinal radiation. TAVR provides an important treatment option for this difficult patient population with desirable procedural safety when using SAVR as a benchmark.

Retrospective Cohort Study Analyzing the Safety and Efficacy of Anti-PD-1 Therapy Following CD30 CAR-T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma

Background: The safety and efficacy of treating pts with relapsed/refractory (r/r) CD30+ lymphomas with chimeric receptor modified T cells targeting the CD30 molecule (CD30.CAR-T) has been recently demonstrated (Grover et al., ASH 2018). Expression of PD-1 on CD30.CAR-T cells has been observed post-infusion at the time of disease recurrence. To determine the safety and efficacy of anti-PD-1 mAb therapy (CPI) post CD30.CAR-T cell therapy, we present a retrospective cohort review of pts with r/r Hodgkin lymphoma (HL) who subsequently received CPI after CD30.CAR-T progression. Methods: We followed and analyzed the clinical outcome of 5 pts with r/r HL who progressed after CD30.CAR-T cell therapy at the University of North Carolina at Chapel Hill and subsequently received CPI to treat relapsed disease. Clinical responses in follow up were determined per local radiologist assessment. Results: Prior to CAR-T cell therapy, the average age of the pts in this cohort was 36 years old (range, 26-54). Four of the five had been treated with CPI prior to CD30.CAR-T therapy, with a median duration of response of 224 days (range, 81-280) and best objective response being a partial response (PR) for all 4 pts. The median time from CPI to CD30.CAR-T therapy was 483 days (range, 25-1174 days). A total of 5 pts have been treated with CPI following clinical progression after CD30.CAR-T. All pts were heavily pre-treated with a median of 8 therapies prior to CD30.CAR-T. One pt received a second infusion of CD30.CAR-T after having stable disease (SD) 6 weeks following the first infusion. Following CD30.CAR-T infusion, 1 pt initially had a complete response (CR), 1 pt had a PR, 2 pts had stable disease (SD), and 1 pt had progressive disease (PD). All 5 pts subsequently developed PD. The median time from CD30.CAR-T to CPI was 132 days (range, 67-393 days), (Table 1). Of the 5 pts evaluable for response, 4 pts achieved a CR and 1 pt achieved a PR (Figure 1). At the time of data cutoff, the median duration of response was 212 days (range 139-836) with ongoing response in 3 pts. Two pts developed recurrent disease following CPI and were again treated with CD30.CAR-T cell therapy, achieving a 2nd CR in both cases. CPI use was associated with the expected toxicities. One pt developed neuropathy, leading to therapy discontinuation after 8 months of therapy. Another pt developed grade 3 colitis, resulting in discontinuation of therapy after 25 months of therapy. A third pt developed pneumonitis (prior mediastinal radiation), with discontinuation of therapy after 8 months of therapy. All pts were still alive at last follow up with a median overall survival of 2.44 years (range, 0.93-2.76) from initial CD30.CAR-T cell therapy. Conclusion: To our knowledge, this is first report of pts with r/r HL who received CPI after CD30.CAR-T cell therapy. Though limited by size, this cohort demonstrates clinical efficacy of CPI after CD30.CAR-T even in those pts who had progressed after previous treatment with CPI. All pts achieved an objective response with CPI administered for relapsed disease after CD30.CAR T cell therapy. Four of five of these patients achieved a CR and 3 patients achieved an improved response when compared to CPI prior to CD30.CAR-T. Combination of CPI and CD30.CAR-T may be an attractive study design in the future for r/r HL. Disclosures Grover: Seattle Genetics: Consultancy. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Savoldo:Baylor College of Medicine: Patents & Royalties: CAR.CD30 patent; Bluebirdbio: Other: research agreement; Cell Medica: Other: Research Agreement; Bellicum: Other: Research Agreement. Serody:Merck: Research Funding; GlaxoSmithKline: Research Funding.

Risk factors for mortality after pericardiectomy for chronic constrictive pericarditis in a large single-centre cohort.

Constrictive pericarditis (CP) is an uncommon disease with multiple causes and unclear clinical outcomes. To date, few publications have clearly defined risk factors of poor outcomes after surgery for CP. We performed a retrospective analysis of almost 100 patients undergoing surgical treatment for CP at a single institution in order to identify risk factors for perioperative and long-term mortality. A total of 97 consecutive patients (67.0% male) undergoing surgery for CP at our institution from 1995 to 2012 were included in the study. CP was diagnosed either preoperatively by cardiac catheterization and appropriate imaging or during surgery. Preoperative and intraoperative risk factors for 30-day and late mortality were analysed using stepwise multivariate logistic and Cox regression analyses. Median follow-up was 1.23 ± 3.96 years (mean 3.08 ± 3.96 years). The mean patient age was 60.0 ± 12.5 years and the underlying aetiology was idiopathic (50.5%), prior cardiac surgery (15.5%), prior mediastinal radiation (9.3%), and miscellaneous (24.7%). All patients underwent either radical (55.2%) or partial (44.8%) pericardiectomy. Concomitant procedures were performed in 54 (55.7%) patients. The total procedure time was 197.0 ± 105.0 min. Cardiopulmonary bypass (CPB) was used in 62 patients with a corresponding CPB time of 124.8 ± 68.4 min. In those patients who underwent CPB, cardioplegic arrest was performed in 53.2% of patients with a mean cross-clamp time of 74.9 ± 41.9 min. Overall 30-day, 1-year and 5-year survival rates were 81.4, 66.5 and 51.6%, respectively, without significant differences according to the underlying aetiology. Multivariate analysis revealed patients with reduced left ventricular ejection fraction (LVEF) [P = 0.01, odds ratio (OR) 3.6] and preoperative right ventricular dilatation (P = 0.04, OR 3.5) to be at significant risk of early mortality. Long-term mortality was independently predicted by the presence of coronary artery disease (CAD) [P < 0.001, hazard ratio (HR) 6.44], chronic obstructive pulmonary disease (P = 0.001, HR 4.21) and preoperative renal insufficiency (P = 0.012, HR 1.8). Concomitant tricuspid valve repair (TVR) appeared to provide protective effect on the long-term survival (P = 0.07). Surgery for CP is associated with a significant risk based on the poor preoperative patient status. Whenever justified, partial over radical pericardiectomy should be preferred and TVR should be indicated liberally. Reduced LVEF and right ventricular dilatation were independent predictors for early mortality, whereas CAD, chronic obstructive pulmonary disease and renal insufficiency were risk factors for late mortality. Thus, an optimal timing for surgery on CP remains crucial to avoid secondary morbidity with an even worse natural prognosis.

Low-Flow, Low-Gradient Severe Aortic Stenosis in the Setting of Constrictive Pericarditis: Clinical Characteristics, Echocardiographic Features, and Outcomes.

Low-flow, low-gradient aortic stenosis (AS), associated with a poor prognosis, can be caused by a reduced stroke volume despite a preserved ejection fraction (left ventricular ejection fraction). We hypothesized that impaired ventricular diastolic filling secondary to constrictive pericarditis (CP) could contribute to reduced transaortic gradients in patients with AS+CP. We sought to examine the characteristics and outcomes of this unique cohort. We analyzed 84 patients with different degrees of AS and preserved left ventricular ejection fraction (≥50%): 28 diagnosed with concomitant CP by echocardiography and 56 patients without CP matched by age, sex, and AS severity during 1998 to 2013. Prior mediastinal radiation (32.1% versus 5.4%; P=0.0072) and cardiac surgery (50.0% versus 3.6%; P=0.0016) were more common in AS+CP patients than those with AS only. AS+CP patients had lower left ventricular stroke volume index and mean transaortic gradients. Five-year survival was 34.3% for AS+CP patients and 89.1% for those with AS only (P<0.001). In univariate analysis, prior mediastinal radiation (hazard ratio, 8.35; 95% confidence interval, 3.38-20.62; P<0.001), reduced left ventricular stroke volume index of <35 mL/m(2) (hazard ratio, 12.52; 95% confidence interval, 3.97-39.48; P<0.001), and concomitant CP (hazard ratio, 13.65; 95% confidence interval, 4.85-38.41; P<0.001) were highly associated with increased mortality. Our findings highlighted the possibility of CP as a pathophysiological mechanism for low-flow, low-gradient AS. Left ventricular stroke volume index and transaortic gradients were commonly reduced in AS in the setting of CP despite a preserved left ventricular ejection fraction, which may result in underestimation of AS severity. Prior mediastinal radiation, lower left ventricular stroke volume index, and concomitant CP were associated with poorer survival in AS patients.

Frequency of Severe Valvular Disease Caused by Mediastinal Radiation Among Patients Undergoing Valve Surgery in a Community‐Based, Regional Academic Medical Center

Our goal was to define the prevalence of radiation-induced valvular heart (RIVD) disease among patients undergoing cardiac valve surgery in a community-based, regional academic medical center. Mediastinal radiation is a treatment modality for various hematologic and solid malignancies; however, long-term cardiac complications, including radiation-induced valvular heart disease, can occur years after the radiation treatments. Mediastinal radiation exposure is an independent risk factor for valvular heart disease often necessitating valve replacement in patients without other risk factors for valve disease. Between January 1, 1998 and September 1, 2007, we retrospectively analyzed our institution's cardiac surgical database over a 10 year period and identified 189 consecutive patients ≤ 50 years of age who underwent valve surgery. Using case-control matching, we assessed the prevalence of mediastinal radiation among these young patients with valve disease necessitating surgery and to their matched controls from all patients admitted to the hospital. Nine individuals (4.8%) were identified as having received previous mediastinal radiation, significantly increased from controls (p<0.0001), and 8 of whom had surgical or pathologic findings consistent with radiation damage. Compared with a matched case-control population, individuals who had severe valve disease and underwent valve replacement had a markedly increased prevalence of prior mediastinal radiation therapy. In conclusion, cardiologists must remain aware of the potential long term valvular complications in patients treated with mediastinal radiation. Increased surveillance for RIVD may be considered in the decades following radiation therapy.

Implantation of a HeartMate II Left Ventricular Assist Device via Left Thoracotomy

Left thoracotomy was used as an approach for the implantation of pulsatile ventricular assist devices. Avoiding the standard approach of median sternotomy is attractive in patients undergoing complicated redo cardiac surgery, especially with prior mediastinal radiation. We report a case of the use of left thoracotomy for the implantation of the HeartMate II axial-flow pump.

Risk factors for development of pneumonitis after high-dose chemotherapy with cyclophosphamide, BCNU and etoposide followed by autologous stem cell transplant

Pneumonitis is a complication of high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) regimens containing BCNU. Our goal was to define the incidence and risk factors for pneumonitis in patients with lymphoma receiving a uniform conditioning regimen in the modern era. We studied 222 patients who received HDC-ASCT using cyclophosphamide, BCNU and VP-16 (CBV). Pneumonitis incidence was 22%, with 19% receiving systemic corticosteroid treatment and 8% requiring inpatient hospitalization for pneumonitis. Three patients died secondary to pneumonitis-related complications. The following variables were independently associated with pneumonitis: prior mediastinal radiation (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.3–18.9, p = 0.0005), total BCNU dose above 1000 mg (OR 3.4, 95% CI 1.3–8.7, p = 0.012) and age less than 54 (OR 3.0, 95% CI 1.4–6.5, p = 0.0037). Increased vigilance for symptoms of pneumonitis is warranted for patients with prior mediastinal radiation and for younger patients, and dose reduction may be considered for patients who would receive greater than 1000 mg of BCNU.

Risk Factors Associated with the Development of Pneumonitis After High-Dose Chemotherapy with Cyclophosphamide, BCNU, and Etoposide (CBV) Followed by Autologous Stem Cell Transplant

AbstractAbstract 903 Background:High-dose chemotherapy (HDC) with autologous stem cell transplant (ASCT) is a standard component of therapy for some patients with hematologic malignancies, particularly those with relapsed or refractory lymphoma. No high-dose chemotherapy regimen has been shown to be superior to another, and thus regimens are chosen based on institutional standards and toxicity profiles. Pneumonitis is a recognized complication of HDC regimens containing BCNU. There has not been a large study of uniformly-treated lymphoma patients to define the incidence and risk factors for developing pneumonitis in the modern era. Methods:We retrospectively examined the medical records of patients who were treated with HDC-ASCT at the Dana-Farber Cancer Institute and Massachusetts General Hospital Cancer Center from 2007–2009 using a regimen containing cyclophosphamide 750 mg/m2 Q12h x4d, BCNU 112.5 mg/m2 daily x4d, and VP-16 (etoposide) 200 mg/m2 Q12h x4d (CBV). Overall (OS) and progression-free survival (PFS), and the incidence of pneumonitis were determined. Univariable and multivariable analyses were performed for characteristics likely to be associated with an increased risk of pneumonitis, which was defined based on a combination of clinical, laboratory, and radiographic factors, with or without bronchoscopy. Results:222 patients were analyzed. The age range was 21–77 (median 54). 61% were male. 71% had non-Hodgkin lymphoma and 29% had Hodgkin lymphoma. The median number of prior chemotherapy regimens was 2; 65% of patients had received prior rituximab, 31% prior bleomycin, and 12% prior gemcitabine. 71% had disease involvement of the mediastinum, and 11% had received prior mediastinal radiation therapy. 43% were past or present smokers. The median follow-up among all living patients was 12 months. The total cumulative incidence of pneumonitis was 22% (49 patients), with 41 patients (19%) receiving corticosteroid treatment, and 18 patients (8%) requiring inpatient hospitalization for pneumonitis. The time range to development of pneumonitis was 26–199 days post-transplant, with a median of 50 days. There were four treatment-related deaths (1.8%): three related to pneumonitis and one related to veno-occlusive disease. On univariable analysis, age, diagnosis of Hodgkin lymphoma, prior mediastinal radiation, prior bleomycin, total BCNU dose delivered, and lack of complete remission status at the time of ASCT were associated with the development of pneumonitis. Gender, body mass index, history of smoking, mediastinal disease involvement, prior rituximab, prior gemcitabine, and pretransplant pulmonary function testing were not found to be statistically significantly different between patients with and without pneumonitis. Stepwise multivariable logistic regression analysis, excluding 31 patients without pneumonitis who had death, relapse, or censoring in the first four months post-transplant, revealed the following variables as independently associated with development of pneumonitis: prior mediastinal radiation (odds ratio 6.5, 95% CI 2.2–18.9, P=0.0005), total BCNU dose above 1000 mg (OR 3.4, 95% CI 1.3–8.7, P=0.012), and age less than 54 (OR 3.0, 95% CI 1.4–6.5, P=0.0037). One year overall survival was 92%, and progression-free survival was 71%. There were no variables, including pneumonitis, associated with PFS on multivariable analysis. Only lack of complete or partial disease response prior to ASCT was associated with inferior OS on multivariable Cox regression modeling (hazard ratio 0.2, 95% CI 0.05–0.72, P=0.01). Conclusions:Pneumonitis is relatively common after HDC-ASCT using CBV conditioning. Increased vigilance for symptoms of pneumonitis is warranted for patients with prior mediastinal radiation and for younger patients. Our data suggests an increased risk with total BCNU dose above 1000 mg, suggesting a possible threshold toxicity effect. Empiric dose reduction may be considered for patients who would receive greater than 1000 mg of BCNU, particularly if they are also younger and/or have had prior mediastinal radiation. Disclosures:No relevant conflicts of interest to declare.

Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines

New anticancer therapies have led to a long life expectancy for many patients; however, treatment-related comorbidities have become an issue for long-term cancer survivors. Cardiac toxicity is one of most feared side-effects of anticancer agents so that the gain in life expectancy due to anticancer therapy might be countered by increased mortality due to cardiac problems, above all heart failure (HF), but also myocardial ischaemia, arrhythmias, hypertension, thromboembolism. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. The incidence of cardiotoxicity depends on different factors related to oncological therapies (type of drug, dose administered during each cycle, cumulative dose, schedule of administration, route of administration, combination of other cardiotoxic drugs or association with radiotherapy) and to patient [age, presence of cardiovascular (CV) risk factors, previous cardiovascular disease (CVD), prior mediastinal radiation therapy]. Adverse cardiotoxic effects induced by chemotherapy are summarized in Table 1.

Conduit choice for coronary artery bypass grafting after mediastinal radiation

Patients who have undergone prior mediastinal radiation might require coronary artery bypass grafting. However, there is some concern regarding potential radiation damage to the internal thoracic artery. Our objective was to assess the late patency of the internal thoracic artery and venous grafts in patients with prior mediastinal radiation. Patients undergoing coronary artery bypass grafting at our clinic after prior mediastinal radiation were identified, and medical records, including operative reports, clinical notes, and coronary angiography, were reviewed. Between 1985 and 2005, 138 patients had coronary artery bypass grafting after mediastinal radiation. Of these, 25 underwent clinically indicated postoperative angiography. The mean patient age was 56.1 +/- 13.8 years, and 24% were female. All patients received between 3000 and 6000 rads in fractionated doses. Seventy-two percent of patients had 3-vessel coronary artery disease. At late angiography (mean, 2.2 years), 6 (32%) of 19 internal thoracic arteries and 13 (27%) of 48 venous or radial arterial conduits showed stenosis of 70% or greater (P = .72). Assessing only grafts that were anastomosed to the left anterior descending coronary artery, 35% (6 of 17) of internal thoracic artery grafts and 60% (3 of 5) of non-internal thoracic artery grafts showed narrowing of 70% or greater (P = .61). Among patients who received a graft to the left anterior descending coronary artery (n = 113), however, age-adjusted survival at 5 years was superior among those receiving an internal thoracic artery graft to the left anterior descending coronary artery. Internal thoracic artery graft patency among patients with prior radiation was less than expected and similar to that for venous grafts, although the effect of conduit disease versus distal target vessel runoff is unknown. Despite this, late survival was superior among those receiving an internal thoracic artery graft to the left anterior descending coronary artery. These data support use of an internal thoracic artery graft to the left anterior descending coronary artery when it appears grossly to be an acceptable conduit.

Gemcitabine-induced pericardial effusion and tamponade after unblocked cardiac irradiation

Gemcitabine therapy has been associated with radiation recall reactions when used in the treatment of carcinoma. We report four cases of hemodynamically significant pericardial effusion in patients with refractory lymphoma who were receiving gemcitabine, all of whom had a history of mediastinal radiation without subcarinal blocking. All four patients had pericardial abnormalities on echocardiography prior to receiving gemcitabine. Two patients required emergent surgical procedures. Of twenty other patients in our practice who received gemcitabine for refractory lymphoma without developing pericardial effusion, none had received prior direct radiation to the heart. The overall response rate of these 24 refractory lymphomas to gemcitabine-containing regimens was 46%. Although gemcitabine-based regimens have clear efficacy in refractory lymphoma, prior mediastinal radiation without subcarinal blocking may be a relative contraindication, especially in the presence of pericardial abnormalities on echocardiography. Physicians should be aware of the potential for developing a gemcitabine-induced radiation recall reaction resulting in hemodynamically significant pericardial effusion.

Left Internal Thoracic Artery Graft Occlusion Following Mediastinal Radiation Therapy

Premature coronary artery disease is a late consequence of mediastinal radiation therapy. Many of these patients have been successfully treated with coronary bypass surgery. A 51-year-old man underwent bypass surgery for severe multivessel coronary disease 18 years following radiation therapy for a posterior mediastinal tumor. Recurrent angina 1 year later occurred following closure of the left internal thoracic artery graft. We suspect that this occurred as a consequence of injury sustained during mediastinal irradiation. Patients who have undergone prior mediastinal radiation therapy may not be assured the excellent long-term patency of the internal thoracic artery graft which has been reported for the general population. Saphenous vein grafts probably should be considered instead.

Intrapericardial abnormalities in patients with pericardial effusion. Findings by two-dimensional echocardiography.

Ten patients with pericardial fluid who also had striking band-like intrapericardial echoes by two-dimensional ultrasonic sector scanning are reported. Four patients had prior mediastinal radiation and four patients had severe renal disease. One patient had purulent pericarditis and one patient had traumatic hemopericardium. The two-dimensional images permitted recognition of loculation of fluid and led to the suspicion of thickened pericardial membranes. Three postradiation patients had both tamponade and constriction; tamponade alone was present in four additional patients. These data are preliminary but suggest that such findings by two-dimensional echocardiography should alert us to consider an effusive-constrictive form of pericardial disease.