Stroke among cancer patients Zaorsky, Nicholas G; Zhang, Ying; Tchelebi, Leila T ...
Nature communications,
11/2019, Letnik:
10, Številka:
1
Journal Article
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We identify cancer patients at highest risk of fatal stroke. This is a population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results program, ...1992-2015. Among 7,529,481 cancer patients, 80,513 died of fatal stroke (with 262,461 person-years at risk); the rate of fatal stroke was 21.64 per 100,000-person years, and the standardized mortality ratio (SMR) of fatal stroke was 2.17 (95% CI, 2.15, 2.19). Patients with cancer of the prostate, breast, and colorectum contribute to the plurality of cancer patients dying of fatal stroke. Brain and gastrointestinal cancer patients had the highest SMRs (>2-5) through the follow up period. Among those diagnosed at <40 years of age, the plurality of strokes occurs in patients treated for brain tumors and lymphomas; if >40, from cancers of the prostate, breast, and colorectum. For almost all cancers survivors, the risk of stroke increases with time.
•Few studies characterize combined immunotherapy and radiation.•Toxicities similar after adding radiation to immunotherapy.•Anti-CTLA-4 associated with more toxicity than anti-PD-1/PD-L1.•No ...significant difference based on timing of immunotherapy and radiation.
Immune checkpoint inhibitor with radiation therapy (ICI + RT) is under investigation for improved patient outcome, so we performed a systematic review/meta-analysis of toxicities for ICI + RT compared to immune checkpoint inhibitor (ICI) therapy alone.
A PRISMA-compliant systematic review of studies in MEDLINE (PubMed) and in the National Comprehensive Cancer Network guidelines was conducted, with primary outcome grade 3 + toxicity. Criteria for ICI alone were: phase III/IV trials that compared immunotherapy to placebo, chemotherapy, or alternative immunotherapy; and for ICI + RT: prospective/retrospective studies with an arm treated with ICI + RT. Meta-analysis was performed by random effects models using the DerSimonian and Laird method. The I2 statistic and Cochran’s Q test were used to assess heterogeneity, while funnel plots and Egger’s test assessed publication bias.
This meta-analysis included 51 studies (n = 15,398), with 35 ICI alone (n = 13,956) and 16 ICI + RT studies (n = 1,442). Our models showed comparable grade 3–4 toxicities in ICI + RT (16.3%; 95% CI, 11.1–22.3%) and ICI alone (22.3%; 95% CI, 18.1–26.9%). Stratification by timing of radiation and irradiated site showed no significant differences, but anti-CTLA-4 therapy and melanoma showed increased toxicity. The grade 5 toxicities were 1.1% and 1.9% for ICI alone and ICI + RT respectively. There was significant heterogeneity, but not publication bias.
The random effects model showed comparable grade 3–4 toxicity in using ICI + RT compared to ICI alone in CNS melanoma metastases, NSCLC, and prostate cancer. ICI + RT is safe for future clinical trials in these cancers.
There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported ...with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.
Primary breast sarcoma (PBS) is a rare and heterogeneous group of malignancies with limited publications. We obtained data from the Surveillance, Epidemiology, and End Results Program and performed ...analysis to determine clinicopathological characteristics of PBS and estimate their associations with overall survival (OS) and cancer-specific survival (CSS). Median age of PBS was 55-59 years and median OS was 108 months. Age, overlap or entire breast involvement, tumor histology, and tumor spread were associated with poor survival outcomes. In the multivariable analysis, tumor size, lymph node involvement, distant metastasis and histologic grade were correlated with survival outcomes (P < 0.001). In M0 patients, mastectomy was associated with worse survival outcomes compared with breast conservative surgery (BCS) (adjusted hazard ratio adjHR, 1.80; 95% CI, 1.31-2.47), regardless of tumor size, tumor grade, tumor histology or radiation history. Adjuvant radiation improved survival outcomes in patients with tumor size >5 cm (adjHR, 0.63; 95% CI, 0.43-0.91), but not in patients with tumor size ≤ 5 cm. Our study demonstrated clinicopathological characteristics of PBS in the US population and supports performing BCS if R0 resection can be achieved, with radiation if tumor size is over 5 cm.
Background
The objectives of this study were to characterize the risk of death (1) from the primary cancer vs competing cause of death; and (2) from various causes of death vs the general poplation. ...The relative risk of death after a pediatric cancer diagnosis versus the general population and the risk of death from a primary cancer diagnosis versus competing causes of death.
Methods
This retrospective, population‐based study used the Surveillance, Epidemiology, and End Results database (1980‐2015) and included patients aged 0 to 19 years at the time of diagnosis. Observed deaths were calculated; the risk of death versus the general population was assessed with standardized mortality ratios (SMRs). Competing risk models for the cause of death were performed.
Results
There were 58,356 patients who were diagnosed, and the mortality rate was 22.8%. To assess causes of death, 6996 patients who died during the study period were included (45,580 total person‐years at risk): 5128 (73%) died of their primary cancer, and 1868 (27%) died of a competing cause. Among all patients, the rate of death from the index cancer was higher than the rate of death from another cause within the first 5 years after diagnosis. The risk of death from a nonprimary cancer began to supersede the rate of death from the primary cancer 10 years after diagnosis for patients with germ cell tumors, lymphomas, and sarcomas. SMRs for the primary cancer were highest within the first 5 years after diagnosis for all cancers (SMRs, 100‐50,000; P < .0001). The risk of death from competing causes (heart disease, suicide, and sepsis) was elevated (SMR, >100; P < .001). The risk of dying of heart disease was high, especially for patients with astrocytomas (SMR, 47.84; 95% confidence interval CI, 27.87‐76.59) and neuroblastomas (SMR, 98.59; 95% CI, 47.28‐181.32). The risk of dying of suicide was high in most patients, particularly for those with osteosarcomas (SMR, 111.40; 95% CI, 2.82‐620.69), Hodgkin lymphomas (SMR, 62.35; 95% CI, 34.89‐102.83), and gonadal germ cell tumors (SMR, 28.97; 95% CI, 12.51‐57.09).
Conclusions
The cause of death for patients with gonadal germ cell tumors, lymphomas, and sarcomas is more commonly a secondary cancer or noncancerous cause than the primary disease; their risk of death from competing causes (heart disease, suicide, and sepsis) rises throughout life.
This study represents one of the first studies of US pediatric patients with cancer to establish the risk of mortality from a primary cancer diagnosis versus secondary cancers and nonneoplastic causes in long‐term analyses. These analyses have demonstrated that over a 30‐year follow‐up period, the risk of mortality for pediatric patients with cancer is significantly higher than the risk for the general population and that certain noncancerous causes of mortality present a particularly increased risk.
Objective
To model the relationship of an area‐based measure of a breast cancer screening and geographic area deprivation on the incidence of later stage breast cancer (LSBC) across a diverse region ...of Appalachia.
Data Source
Central cancer registry data (2006–2008) from three Appalachian states were linked to Medicare claims and census data.
Study Design
Exploratory spatial analysis preceded the statistical model based on negative binomial regression to model predictors and effect modification by geographic subregions.
Principal Findings
Exploratory spatial analysis revealed geographically varying effects of area deprivation and screening on LSBC. In the negative binomial regression model, predictors of LSBC included receipt of screening, area deprivation, supply of mammography centers, and female population aged >75 years. The most deprived counties had a 3.31 times greater rate of LSBC compared to the least deprived. Effect of screening on LSBC was significantly stronger in northern Appalachia than elsewhere in the study region, found mostly for high‐population counties.
Conclusions
Breast cancer screening and area deprivation are strongly associated with disparity in LBSC in Appalachia. The presence of geographically varying predictors of later stage tumors in Appalachia suggests the importance of place‐based health care access and risk.
Abstract
Pancreatic cancer is a highly fatal malignancy for which surgery is currently considered to be the only curative treatment. However, less than a quarter of patients have disease amenable to ...definitive surgical resection. Local treatment with radiation therapy is a promising alternative to surgery for those patients with unresectable disease. However, conventional radiation techniques with computed tomography (CT)-guided therapy have yielded disappointing results due to the inability to deliver ablative doses of ionizing radiation, while sparing the radiosensitive adjacent organs at risk. Magnetic resonance-guided radiotherapy (MRgRT) has emerged as an alternative to CT-guided radiation treatment which allows for the delivery of higher doses of radiation with low toxicity to surrounding structures. Further study into the use of MRgRT and dose escalation for locally advanced unresectable pancreatic cancer is needed.
Abstract
BACKGROUND
Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences ...in the pretreatment nidus volumes.
OBJECTIVE
To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features.
METHODS
We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation.
RESULTS
The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts.
CONCLUSION
This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.
Graphical Abstract
Graphical Abstract
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