Uncrossable and undilatable lesions-A practical approach to optimizing outcomes in PCI.

Uncrossable lesions are those that cannot be crossed with a balloon after successful guidewire crossing. These lesions are challenging and are commonly encountered in tortuous and calcified arteries as well as chronic total occlusions. They are the second most common barrier to successful PCI in CTO intervention after inability to cross the CTO segment with a guidewire. Procedures involving balloon uncrossable lesions during routine and CTO PCI utilise longer procedural times, radiation dose and contrast volumes with a lower likelihood of procedural success. In this article, we describe a pragmatic approach of managing balloon uncrossable lesions utilising the most contemporary equipment available in an algorithmic fashion beginning with simple, cost effective techniques right up to complex strategies for advanced operators. In addition, some of these lesions, even when crossed by any technique, they may remain difficult to dilate and prepare for stent insertion. We describe an approach of how to manage these undilatable lesions.

Transradial Secondary Access to Guide Valve Implantation and Manage Peripheral Vascular Complications During Transcatheter Aortic Valve Implantation.

BACKGROUND: Vascular complications from transfemoral (TF) secondary access during transcatheter aortic valve implantation (TAVI) are common. We compare our experience of transradial (TR) versus transfemoral secondary access during TAVI and describe techniques for performing iliofemoral arterial intervention from the transradial approach. METHODS: All TAVI procedures with a single secondary access were included. Demographics, procedural details and 30-day outcomes were recorded. VARC-2 criteria were used for procedural complications. Procedures with TF primary access were stratified by the site of secondary arterial access. RESULTS: Single secondary access was used in 199 cases, of which 20 were performed via non-TF access. Of the 179 TF primary access cases, 115 (64%) used TR secondary access and 64 (36%) used TF secondary access. In the TR cohort percutaneous vascular intervention was performed from the transradial approach in 19 cases (17%). Emergent TF secondary access was not required in any case. There were no differences in procedural time, radiation dose, contrast use, bleeding complications, stroke or mortality between the groups. There was one secondary access complication in the TF cohort and none in the TR cohort. CONCLUSIONS: Transradial (TR) secondary access during TAVI is safe and feasible and may reduce the secondary access site vascular complication rate. With appropriate equipment, most peripheral vascular complications can be managed entirely via TR access avoiding unplanned femoral arterial access. TR secondary access should be considered the default approach for non-TF TAVI cases and can be considered for all TF cases as long as dedicated equipment is available.

Survival Outcomes of Dose-Escalated External Beam Radiotherapy versus Combined Brachytherapy for Intermediate and High Risk Prostate Cancer Using the National Cancer Data Base.

PURPOSE: We evaluated survival outcomes between dose-escalated EBRT (external beam radiotherapy) vs EBRT plus brachytherapy for intermediate and high risk prostate cancer using NCDB (National Cancer Data Base). MATERIALS AND METHODS: Patients with cN0M0 prostate cancer treated from 2004 to 2006 were divided into radiotherapy comparison groups, including EBRT alone (75.6 to 81 Gy) and EBRT (40 to 50.4 Gy) plus brachytherapy with EBRT delivered at 1.8 to 2.0 Gy per fraction. Brachytherapy data were limited to yes/no with no information on modality, dose or schedule. Eligible patients were known to have received androgen deprivation therapy. Overall survival was evaluated using multivariate Cox regression and propensity score matched analyses. RESULTS: Of the 20,279 study patients with prostate cancer, including 12,617 at intermediate risk and 7,662 at high risk, 71.3% received EBRT alone and 28.7% received EBRT plus brachytherapy. Median followup was 82 months (range 3 to 120) and median age was 70 years (range 36 to 90). On multivariate analysis compared to EBRT alone (75.6 to 81 Gy) EBRT plus brachytherapy was associated with improved survival (HR 0.75, p <0.001). This significance remained consistent for intermediate and high risk when analyzed separately (HR 0.73 and 0.76, respectively, each p <0.001). However on subset analysis compared to very high dose EBRT alone (79.2 to 81 Gy) in all patients combined EBRT plus brachytherapy was not associated with improved survival (HR 0.91, p = 0.083). CONCLUSION: Compared to EBRT (75.6 to 81 Gy) we observed an association of EBRT plus brachytherapy with a decreased risk of death in men with intermediate and high risk prostate cancer. However this association was no longer significant when EBRT doses of 79.2 to 81 Gy were used.

Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared.

Septal Hematoma: A Rare But Potentially Serious Complication of Retrograde CTO-PCI.

The uptake of CTO-PCI and the use of the hybrid approach have increased widely; this has resulted in a new set of complications, some of which are unusual, particularly with the retrograde approach. We present a case of a rare complication of septal collateral perforation resulting in the formation of septal hematoma that fortunately on this occasion did not result in any significant clinical deterioration, and was managed conservatively with a successful outcome. However, on other occasions, the outcome can be more serious.

Inferior outcomes and treatment disparities in elderly patients with classical Hodgkin lymphoma: a national cancer data base analysis.

Elderly patients with classical Hodgkin lymphoma (cHL) are understudied and poorly defined. The National Cancer Data Base was queried for adults with cHL diagnosed 2004-2013: 22,547 age 18-39, 12,841 age 40-59, and 10,873 age ≥60 were identified. Two-year overall survival (OS) was 97%, 91%, and 65% for the three age cohorts, respectively (p < .0001). Elderly patients age ≥60 had greater advanced comorbidity scores, stage III-IV disease, and lymphocyte-depleted histology. Elderly patients were treated less with chemotherapy, radiotherapy for stage I-II disease, and at academic/research centers (p < .001). There was improved OS in elderly patients who received chemotherapy and/or radiotherapy and were treated at academic/research centers. This largest analysis of elderly cHL demonstrates that patients ≥60 are distinct from those 40-59. Age ≥60 should be a stratification in future trials and merit distinct studies. Improving the poor rate of treatment delivery and directing care to academic centers may improve outcomes.

Patterns of Adjuvant Therapy Utilization in Uterine Carcinosarcoma Stages I to III: A National Cancer Database Analysis.

OBJECTIVE: The objective of this study is to characterize patterns of utilization of adjuvant chemotherapy (CT) and radiotherapy (RT) in the posthysterectomy management of uterine carcinosarcoma (UCS) in the United States. MATERIALS AND METHODS: We queried the National Cancer Database for women diagnosed with UCS between 2004 and 2012 and undergoing hysterectomy. Logistic regression was performed to identify sociodemographic, facility-specific, and treatment-related predictors of receiving multiagent chemotherapy, external beam radiotherapy (EBRT), or brachytherapy (BT). RESULTS: In total 4272 patients were included, with 2 in 5 (40.5%) receiving no adjuvant therapy. Regarding RT, 2357 (55.1%) received neither EBRT nor BT, 929 (21.7%) received EBRT alone, 518 (12.1%) received BT alone, and 468 (11.0%) received EBRT+BT. Most women (70.8%) received no CT, a minority (1.5%) received single-agent CT, and the rest (27.8%) received multiagent chemotherapy. Logistic regression demonstrated disparities in receipt of adjuvant therapies by age, diagnosis year, insurance, facility volume, facility type, stage, and margin status, with patients with positive surgical margins less likely to receive BT. CONCLUSIONS: Following hysterectomy for UCS, a large proportion of women receives no CT and no RT in the United States. Multispecialty evaluation is critical for individualization of therapy and may address disparities in this aggressive disease.

Patterns of Fractionation and Boost Usage in Adjuvant External Beam Radiotherapy for Ductal Carcinoma in Situ in the United States.

BACKGROUND: While the roles of hypofractionated (HFxn) radiotherapy and lumpectomy boost in the adjuvant management of invasive breast cancer are supported by the results of clinical trials, randomized data supporting their use for ductal carcinoma in situ (DCIS) are forthcoming. We sought to evaluate current national trends and identify factors associated with HFxn and boost usage using the National Cancer Database. PATIENTS AND METHODS: We queried the National Cancer Database for women diagnosed with DCIS from 2004 to 2014 undergoing external beam radiotherapy after breast conservation surgery. Patients were categorized as receiving either conventional fractionation (CFxn) or HFxn and as either receiving or not receiving a boost. Multiple logistic regression was performed to identify demographic, clinical, and treatment factor associations. RESULTS: A total of 101,615 women were identified, with 87,641 (86.2%) receiving CFxn, 13,974 (13.8%) receiving HFxn, and most patients in each group (84.9% and 57.7%, respectively) receiving a boost. Implementation of HFxn increased from 4.3% in 2004 to 33.0% in 2014, and the use of a boost declined from 83.3% to 74.6%. HFxn receipt was independently associated with later year of diagnosis, older age, higher income, greater distance from treatment facility, greater facility volume, academic facility type, Western residence, smaller lesions, and nonreceipt of a boost. Factors associated with boost receipt included earlier year of diagnosis, younger age, higher income, community facility type, adverse pathologic features, and nonreceipt of HFxn. CONCLUSION: Although CFxn with a boost remains the most common external beam radiotherapy strategy for DCIS, implementation of HFxn without a boost appears to be increasing. Practice patterns at present seem to be driven by guidelines for invasive breast cancer and nonclinical factors.

Outcomes after culprit-only percutaneous coronary intervention for multivessel disease during ST-segment elevation myocardial infarction: a comparison of registry and clinical trial outcomes.

BACKGROUND: The PRAMI and CvLPRIT trials support preventive percutaneous coronary intervention (PCI) for multivessel coronary disease found during ST-segment elevation myocardial infarction (STEMI). We assess our real-world experience of the management of multivessel disease identified during primary PCI (PPCI) in a large UK regional centre. PATIENTS AND METHODS: All STEMI patients who underwent culprit-only PPCI during the study period (August 2011 to August 2013) were retrospectively assessed for eligibility to each trial. The two resulting groups were designated as the 'observational' cohorts. Primary outcomes were then determined and compared with the culprit-only revascularisation cohorts from the respective published randomized controlled trials (RCTs). RESULTS: A total of 1143 consecutive cases were presented during the study period. Of these, 343 would have been suitable for inclusion to PRAMI and were included in the 'observational PRAMI' cohort; 196 patients were included in the 'observational CvLPRIT' cohort.The 'observational PRAMI' cohort experienced fewer primary outcome events (13.1 vs. 22.9%), cardiac deaths (0.6 vs. 4.3%) and nonfatal myocardial infarctions (3.5 vs. 8.7%) than the culprit-only PCI PRAMI cohort (n=231); there were significantly more diabetics (P=0.022) and anterior STEMI initial presentations in the culprit-only PCI PRAMI cohort. Primary outcomes were comparable to those of the preventive PCI PRAMI cohort.The 'observational CvLPRIT' cohort showed no significant difference in primary outcomes over 12 months (16.8 vs. 21.2%), but significantly lower all-cause mortality (2 vs. 6.9%) than the culprit-only PCI CvPLRIT cohort (n=146). The 30-day event rates were similar to the preventive PCI arm; the 12-month events were better than the nonpreventive, but not as good as the preventive RCT cohorts. CONCLUSION: Outcomes from culprit-only primary PCI for multivessel disease in patients selected by the RCT criteria from an all-comers population representing real-life experience are better than those published in the two main RCTs. The RCTs may have selected a high-risk population for study exaggerating the benefits of preventive PCI.

Prostate brachytherapy, either alone or in combination with external beam radiation, is associated with longer overall survival in men with favorable pathologic Group 4 (Gleason score 8) prostate cancer.

PURPOSE: Conventional prostate cancer risk stratification results in considerable heterogeneity within each prognostic group. Men with pathologic grade Group 4 (Gleason score 8) but otherwise low-risk features have been identified as a favorable subset of high-risk prostate cancer. Given recent randomized data supporting improved cancer outcome with brachytherapy in intermediate- and high-risk prostate cancer, we sought to evaluate brachytherapy utilization and overall survival (OS) for these patients. METHODS AND MATERIALS: We queried the National Cancer Database for clinical T1c-T2a N0 M0 prostate cancer with prostate-specific antigen <10 ng/mL and Gleason score 8 adenocarcinoma on biopsy. All patients received androgen deprivation therapy and either external beam radiation therapy (EBRT) alone, brachytherapy alone, or a combination of EBRT with brachytherapy boost (brachytherapy + EBRT). Kaplan-Meier OS estimates as well as univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score-matched analyses were performed to further control for baseline confounders. RESULTS: Four thousand four hundred ninety-six patients were identified with a median followup of 62.5 months (range, 2.3-119.8). Median age was 72 years (range, 41-90+). Utilization of brachytherapy decreased from 2004 to 2009. The odds ratio for brachytherapy by year (continuous variable) was 0.86 (p < 0.001). Five-year OS was 84%, 88%, and 89% for the EBRT alone, brachytherapy alone, and brachytherapy + EBRT groups, respectively. On multivariate analysis, higher median income, low comorbidity score, and treatment with brachytherapy alone (hazard ratio, 0.66; p = 0.005) or brachytherapy + EBRT (hazard ratio, 0.70; p = 0.001) remained associated with longer OS. Propensity score matching confirmed longer OS associated with either brachytherapy regimen. CONCLUSIONS: Of those men with World Health Organization pathologic grade Group 4 (Gleason score 8) prostate cancer and otherwise favorable prognostic features treated with androgen deprivation therapy and radiation therapy, longer OS was achieved when prostate brachytherapy was included, whether used alone or in combination with supplemental EBRT. In spite of these excellent outcomes, prostate brachytherapy utilization is declining in the United States.

The Impact of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma.

INTRODUCTION: The optimal role for postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. We used the National Cancer Data Base to investigate the impact of PORT on overall survival (OS). METHODS: Patients who underwent an operation for thymoma or thymic carcinoma were categorized into Masaoka-Koga stage groups I to IIA, IIB, III, and IV. Patients who did not undergo an operation or those who received preoperative radiation were excluded. Kaplan-Meier estimates of OS and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score-matched analyses were performed to further control for baseline confounders. RESULTS: From 2004 to 2012, 4056 patients were eligible for inclusion, 2001 of whom (49%) received PORT. On multivariate analysis of OS in the thymoma cohort adjusted for age, WHO histologic subtype, Masaoka-Koga stage group, surgical margins, and chemotherapy administration, PORT was associated with superior OS (hazard ratio [HR] = 0.72, p = 0.001). Propensity score-matched analyses confirmed the survival advantage associated with PORT. Subset analysis indicated longer OS in association with PORT for patients with stage IIB thymoma (HR = 0.61, p = 0.035), stage III (HR = 0.69, p = 0.020), and positive margins (HR = 0.53, p < 0.001). The impact of PORT for stage I to IIA disease did not reach significance (HR = 0.76, p = 0.156). CONCLUSIONS: In this large database analysis of PORT for thymic tumors, PORT was associated with longer OS, with the greatest relative benefits observed for stage IIB to III disease and positive margins. In the absence of randomized studies assessing the value of PORT, these data may inform clinical practice.

Treatment Selection and Survival Outcomes With and Without Radiation for Unresectable, Localized Intrahepatic Cholangiocarcinoma.

PURPOSE: Most patients with intrahepatic cholangiocarcinoma present with locally advanced disease not amenable to surgical resection. For these inoperable patients, chemotherapy alone is generally considered the standard of care, with limited data regarding the role of radiotherapy. We used the National Cancer Database to investigate care patterns and the impact of radiation as a component of combined modality therapy on overall survival. METHODS: We queried the National Cancer Database for patients with nonmetastatic intrahepatic cholangiocarcinoma diagnosed from 2001 to 2011. Those undergoing surgery were excluded. All included patients were coded as having received chemotherapy. Kaplan-Meier overall survival estimates and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score-matched analysis was performed to account for indication bias and mitigate heterogeneity between treatment groups. RESULTS: One thousand six hundred thirty-six patients were identified with a median follow-up of 11.3 months. Median age was 63 years; 23% received combined modality therapy with radiation. Two-year overall survival for the entire cohort was 21%, and for the chemotherapy-alone and combined modality therapy groups, it was 20% versus 26%, respectively. On univariate analysis, overall survival was improved with combined modality therapy. On multivariate analysis, combined modality therapy remained significantly associated with improved overall survival, as did younger age, female sex, higher median income, lower comorbidity score, and earlier stage. Propensity score matched analysis confirmed the overall survival benefit associated with combined modality therapy. DISCUSSION: In this largest reported analysis of combined modality therapy for localized, inoperable intrahepatic cholangiocarcinoma, the addition of radiation to chemotherapy was associated with an improvement in overall survival. Three quarters of inoperable patients in the United States do not receive radiation. Survival remains relatively poor for all patients, and we enthusiastically support ongoing randomized trials seeking to incorporate radiotherapy as a possible means to improve outcomes.

Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis.

BACKGROUND: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. METHODS AND MATERIALS: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. RESULTS: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. CONCLUSION: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease.

Survival outcomes of combined external beam radiotherapy and brachytherapy vs. brachytherapy alone for intermediate-risk prostate cancer patients using the National Cancer Data Base.

PURPOSE: The purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate-risk prostate cancer, using the National Cancer Data Base. METHODS AND MATERIALS: The National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate-specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40-50.4 Gy) plus brachytherapy and brachytherapy alone. RESULTS: A total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2-122 months); median age was 68 years (40-90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively (p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75-0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75-0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10-20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77-0.98; p = 0.026). CONCLUSIONS: EBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic.

Clinical potential of bevacizumab in the treatment of metastatic and locally advanced cervical cancer: current evidence.

The addition of bevacizumab to established therapies for metastatic and locally advanced cervical cancer is an area of evolving research and a potential strategy toward improving historically suboptimal outcomes for women with advanced disease. Bevacizumab, when added to first-line chemotherapy, has now been shown to improve overall survival among women with metastatic cervical cancer, and recent Phase II data suggests it is safe and effective for patients with locally advanced disease treated with curative intent. Here we review the rationale and current evidence for bevacizumab in clinical practice, with an emphasis on the emerging role of bevacizumab in the treatment of metastatic and locally advanced cervical cancer.

High-grade prostate cancer: favorable results in the modern era regardless of initial treatment.

Purpose. We performed a retrospective study to determine the outcome of a modern cohort of patients with high-grade (Gleason score ≥ 8) prostate cancer treated with radical prostatectomy, radiation therapy, or hormone therapy. Methods. We identified 404 patients in the South Texas Veteran's Healthcare System Tumor Registry diagnosed with high grade prostate cancer between 1998 and 2008. Mean follow-up was 4.62 ± 2.61 years. End points were biochemical failure-free survival, overall survival, metastasis-free survival, and cancer-specific survival. Results. 5-year overall survival for patients undergoing radical prostatectomy, radiation therapy, and hormone therapy was 88.9%, 76.3%, and 58.9%, respectively. 5-year metastasis-free survival for patients undergoing radical prostatectomy, radiation therapy, and hormone therapy was 96.8%, 96.6%, and 88.4%, respectively, and 5-year cancer-specific survival was 97.2%, 100%, and 89.9%, respectively. Patients with a Gleason score of 10 and pretreatment prostate-specific antigen > 20 ng/mL had decreased 5-year biochemical failure-free and cancer-specific survival. Patients with a pretreatment prostate-specific antigen > 20 ng/mL had decreased 5-year overall survival. Discussion. Even for patients with high-grade disease, the outcome is not as dire in the modern era regardless of primary treatment modality chosen. While there is room for improvement, we should not have a nihilistic impression of how these patients will respond to treatment.