OBJECTIVESApical ballooning syndrome (ABS) is a transient cause of ventricular dysfunction. The aim of this study was to determine the clinical and hemodynamic correlates of brain natriuretic peptide ...(BNP) levels in ABS and compare the biomarker profiles in ABS with acute myocardial infarction controls.
METHODSFifty-seven prospectively diagnosed patients with ABS whose BNP and troponin T level measurements were available were included. Fifty patients with ST-elevation myocardial infarction (STEMI) and 25 individuals with non-ST-elevation myocardial infarction (NSTEMI) were included as matched controls.
RESULTSIn the ABS cohort, the BNP levels were higher in patients older than 65 years compared with younger individuals767 (269, 951) versus 340 (131, 904.5), P=0.019. There were no significant correlations between BNP levels and hemodynamic parameters such as left ventricular ejection fraction and end diastolic pressure. There were no correlations between BNP and peak troponin T (r=0.03, P=0.8). BNP levels were significantly higher in ABS patients when compared with the STEMI and NSTEMI controls. The BNP to peak troponin T ratio was significantly higher in ABS compared with the STEMI controls 1089.4 (446.7, 3334.8) versus 97.4 (17.9, 264.7), P=0.04.
CONCLUSIONBNP elevation is almost universal in ABS. Cardiac hemodynamic indices do not correlate with BNP levels. The magnitude of BNP elevation is higher in ABS compared with STEMI and NSTEMI.
Radiation therapy (RT) is a mainstay of cancer care, and accumulating evidence suggests the potential for synergism with components of the immune response. However, few data describe the tumor immune ...contexture in relation to RT sensitivity. To address this challenge, we used the radiation sensitivity index (RSI) gene signature to estimate the RT sensitivity of >10,000 primary tumors and characterized their immune microenvironments in relation to the RSI.
We analyzed gene expression profiles of 10,469 primary tumors (31 types) within a prospective tissue collection protocol. The RT sensitivity of each tumor was estimated by the RSI and respective distributions were characterized. The tumor biology measured by the RSI was evaluated by differentially expressed genes combined with single sample gene set enrichment analysis. Differences in the expression of immune regulatory molecules were assessed and deconvolution algorithms were used to estimate immune cell infiltrates in relation to the RSI. A subset (n = 2368) of tumors underwent DNA sequencing for mutational frequency characterization.
We identified a wide range of RSI values within and across various tumor types, with several demonstrating nonunimodal distributions (eg, colon, renal, lung, prostate, esophagus, pancreas, and PAM50 breast subtypes; P < .05). Across all tumor types, stratifying RSI at a tumor type-specific median identified 7148 differentially expressed genes, of which 146 were coordinate in direction. Network topology analysis demonstrates RSI measures a coordinated STAT1, IRF1, and CCL4/MIP-1β transcriptional network. Tumors with an estimated high sensitivity to RT demonstrated distinct enrichment of interferon-associated signaling pathways and immune cell infiltrates (eg, CD8
T cells, activated natural killer cells, M1-macrophages; q < 0.05), which was in the context of diverse expression patterns of various immunoregulatory molecules.
This analysis describes the immune microenvironments of patient tumors in relation to the RSI gene expression signature.
Purpose
Leptomeningeal disease (LMD) is an advanced metastatic disease presentation portending a poor prognosis with minimal treatment options. The advent and widespread use of new systemic therapies ...for metastatic breast cancer has improved systemic disease control and extended survival; however, as patients live longer, the rates of breast cancer LMD are increasing.
Methods
In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of breast cancer LMD.
Results
We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, intrathecal, surgical, and radiotherapy treatment modalities), and treatment response evaluation specific to breast cancer patients. Furthermore, we discuss the controversies within this unique clinical setting and identify potential clinical opportunities to improve upon the diagnosis, treatment, and treatment response evaluation in the management of breast LMD.
Conclusions
We recognize the shortcomings in our current understanding of the disease and explore the future role of genomic/molecular disease characterization, technological innovations, and ongoing clinical trials attempting to improve the prognosis for this advanced disease state.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The treatment of oligometastatic disease has become common as imaging techniques have advanced and the management of systemic disease has improved. Use of highly targeted, hypofractionated regimens ...of stereotactic body radiotherapy (SBRT) is now a primary management option for patients with oligometastatic disease.
The properties of SBRT are summarized and the results of retrospective and prospective studies of SBRT use in the management of oligometastases are reviewed. Future directions of SBRT, including optimizing dose and fractionation schedules, are also discussed.
SBRT can deliver highly conformal, dosed radiation treatments for ablative tumors in a few treatment sessions. Phase 1/2 trials and retrospective institutional results support use of SBRT as a treatment option for oligometastatic disease metastasized to the lung, liver, and spine, and SBRT offers adequate toxicity profiles with good rates of local control. Future directions will involve optimizing dose and fractionation schedules for select histologies to improve rates of local control while limiting toxicity to normal structures.
SBRT offers an excellent management option for patients with oligometastases. However, additional research is still needed to optimize dose and fractionation schedules.
Background
Penile cancer (PeCa) is a rare, aggressive malignancy often associated with the human papillomavirus (HPV). The practice of a personalized risk-adapted approach is not yet established. ...This study is to assess the relationship between HPV tumor status and chemoradiotherapy (CRT) in PeCa locoregional control (LRC).
Methods
We retrospectively identified patients with HPV status who were diagnosed with squamous cell carcinoma of the penis and treated with surgical resection between 1999 and 2016. The relationship between tumor/treatment characteristics and LRC were analyzed with univariate and multivariate Cox proportional hazard regression analysis (UVA and MVA, respectively). Time-to-event outcomes were estimated with Kaplan–Meier curves and compared via log-rank tests.
Results
Fifty-one patients were identified. The median follow-up was 36.6 months. Patients were primarily HPV-negative (HPV−) (
n
= 28, 55%), and pathologic node positive (pN+) (55%). The 2 year LRC rate was 54%. pN+ patients had a significantly lower 2 year LRC (37 vs. 81%,
p
= 0.002). In the subgroup analysis of pN+ patients (
n
= 28), there was a LRC benefit associated with the addition of CRT (HR 0.19; 95% CI 0.05–0.70,
p
= 0.012) and HPV-positive (HPV+) disease (HR 0.18; 95% CI 0.039–0.80,
p
= 0.024) using MVA. HPV+ patients treated with CRT had improved 2 year LRC compared to HPV− patients (83 vs. 38%,
p
= 0.038).
Conclusions
Adjuvant CRT and HPV+ disease independently predicted for improved LRC in pN+ PeCa. In HPV+ PeCa, the LRC benefit was primarily observed in patients treated with adjuvant CRT. Prospective investigation of HPV+ and CRT is required to further delineate their roles in optimizing PeCa treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Leptomeningeal disease is a rare presentation of advanced metastatic breast cancer. The purpose of this study was to evaluate craniospinal progression between intrathecal (IT) trastuzumab, IT ...chemotherapy, and whole brain radiation therapy (WBRT) in leptomeningeal disease.
Methods
A total of 56 patients were identified with breast cancer leptomeningeal disease at our institution treated with IT trastuzumab (
n
= 18; 32%), single-agent IT chemotherapy (methotrexate
n
= 14 or thiotepa
n
= 1; 27%), or WBRT alone (
n
= 23; 41%). Patients were treated beginning November 2012 and followed until November 2018.
Results
Median time from breast cancer diagnosis to development of leptomeningeal disease was 4.3 years. There were no significant differences noted between IT trastuzumab, IT chemotherapy, or WBRT groups in age (
p
= 0.4), Karnofsky Performance Status (KPS) (
p
= 0.07), or receipt of systemic therapy at time of leptomeningeal disease treatment (
p
= 0.47). Median follow-up of patients from leptomeningeal diagnosis was 5 months (range 0.2–81.1 months). Significant differences were noted in Kaplan–Meier (KM) craniospinal progression-free survival (CS-PFS) with 6-month rates of 44%, 18%, and 26% (
p
= 0.04) between IT trastuzumab, IT chemotherapy, and WBRT, respectively. Craniospinal control > 10 months was achieved in four patients treated with IT trastuzumab. Twelve-month KM OS rates were 54%, 10%, and 19% (
p
= 0.01) between IT trastuzumab, IT chemotherapy, and WBRT groups, respectively. IT therapy was adequately tolerated with three patients undergoing treatment-related hospitalizations.
Conclusions
In our institutional series, significant differences were noted in CS-PFS and OS by treatment modality. IT trastuzumab should be considered in the management HER2+ breast leptomeningeal disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System Metastases in Tampa, Florida. The meeting included ...investigators from multiple academic centers and disciplines. A consensus summary of the progress and challenges in melanoma parenchymal brain metastases was published (Eroglu et al., Pigment Cell & Melanoma Research, 2019, 32, 458). Here, we will describe the current state of basic, translational, clinical research, and therapeutic management, for melanoma patients with leptomeningeal disease. We also outline key challenges and barriers to be overcome to make progress in this deadly disease.
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Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Purpose
Awareness of inherited breast cancer has increased bilateral prophylactic mastectomy (BPM) among unaffected genetic mutation carriers, yet many still choose surveillance. We aimed to identify ...differences among women electing BPM vs high-risk surveillance.
Methods
Participants from an IRB-approved database recruited from 11/2000 to 01/2017 with a deleterious/pathogenic, variant suspected deleterious, or likely pathogenic mutation in ≥ 1 of 11 genes with increased risk for breast cancer (per 2017 NCCN guidelines) were identified. Participants with breast cancer and males were excluded. Sociodemographic and clinical data were collected. The BPM and high-risk surveillance groups were compared using Wilcoxon, Fisher’s Exact, and Pearson’s Chi-Square analyses.
Results
A total of 304 unaffected genetic mutation carriers were identified; 22 men were excluded. 113/282 (40%) underwent BPM. There was no significant difference in age, race, marital status, high school graduates, family history of breast cancer, breast biopsies, chemoprevention use, or understanding implications of genetic mutation carriage. BPM participants were more likely to have a prior pregnancy (
p
= 0.0005), college education (
p
= 0.04), income > $50,000/year (
p
= 0.01), first-degree relative with breast cancer (
p
= 0.04), higher total number of relatives with breast cancer (
p
= 0.01), and rate of risk-reducing salpingo-oophorectomy (
p
= < 0.0001). The high-risk surveillance group was more likely to have a history of ovarian cancer (
p
= 0.009) and cancer worry (
p
= < 0.0001).
Conclusions
BPM is a common but not universal choice among unaffected genetic carriers of inherited breast cancer syndromes. Parity, education, income, ovarian cancer history, first-degree relatives with breast cancer, and cancer worry play significant roles in these decisions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at a particularly high risk of breast cancer brain metastasis (BCBM) and leptomeningeal disease (LMD). ...Improvements in systemic therapy have translated to improved survival for patients with HER2-positive BCBM and LMD. However, the optimal management of these cases is rapidly evolving and requires a multidisciplinary approach. Herein, a team of radiation oncologists, medical oncologists, neuro-oncologists, and breast surgeon created a review of the evolving management of HER2-positive BCBM and LMD. We assess the epidemiology, diagnosis, and evolving treatment options for patients with HER2-positive BCBM and LMD, as well as the ongoing prospective clinical trials enrolling these patients. The management of HER2-positive BCBM and LMD represents an increasingly common challenge that involves the coordination of local and systemic therapy. Advances in systemic therapy have resulted in an improved prognosis, and promising targeted therapies currently under prospective investigation have the potential to further benefit these patients.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To report outcomes and toxicity for patients with oligometastatic (≤5 lesions) prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT).
Seventeen men with 21 PCa lesions were ...treated with SBRT between February 2009 and November 2011. All patients had a detectable prostate-specific antigen (PSA) at the time of SBRT, and 11 patients (65%) had hormone-refractory (HR) disease. Treatment sites included bone (n = 19), lymph nodes (n = 1), and liver (n = 1). For patients with bone lesions, the median dose was 20 Gy (range, 8-24 Gy) in a single fraction (range, 1-3). All but two patients received some form of anti-androgen therapy after completing SBRT.
Local control (LC) was 100%, and the PSA nadir was undetectable in nine patients (53%). The first post-SBRT PSA was lower than pre-treatment levels in 15 patients (88%), and continued to decline or remain undetectable in 12 patients (71%) at a median follow-up of 6 months (range, 2-24 months). Median PSA measurements before SBRT and at last follow-up were 2.1 ng/dl (range, 0.13-36.4) and 0.17 ng/dl (range, <0.1-140), respectively. Six (55%) of the 11 patients with HR PCa achieved either undetectable or declining PSA at a median follow-up of 4.8 months (range, 2.2-6.0 months). Reported toxicities included one case each of grade 2 dyspnea and back pain, there were no cases of grade ≥3 toxicity following treatment.
We report excellent LC with SBRT in oligometastatic PCa. More importantly, over half the patients achieved an undetectable PSA after SBRT. Further follow-up is necessary to assess the long-term impact of SBRT on LC, toxicity, PSA response, and clinical outcomes.
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