A B S T R A C T PurposeFive-year survival rates for childhood cancer have improved over the past four decades. However, it is unknown whether changes in primary cancer therapy have improved rates of long-term (Ͼ 5 years from diagnosis) durable remissions and reduced treatment-related deaths. We investigated changes in patterns of late mortality over time and cause-specific attribution of late-mortality among 5-year survivors. Patients and MethodsUsing data from the Surveillance, Epidemiology and End Results (SEER) population-based registry, we assessed all-cause and cause-specific (recurrence/progression of primary disease, external cause, and nonrecurrence/nonexternal cause) late mortality during four consecutive time periods from 1974 through 2000 among 26,643 5-year survivors of childhood cancer. ResultsAll-cause late mortality improved during more recent eras, dropping from 7.1% (95% CI, 6.4% to 7.8%) among children diagnosed during 1974 to 1980 to 3.9% (95% CI, 3.3% to 4.4%) among children diagnosed during 1995 to 2000 (P Ͻ .001), largely because of reduced mortality from recurrence or progression. While there was no significant reduction in mortality attributable to other health conditions (including treatment-related health conditions), analysis controlling for demographic characteristics identified a trend toward reduced risk during more recent eras (P ϭ .007). Disparity by race/ethnicity was identified, with higher mortality among non-Hispanic blacks than among non-Hispanic whites for all-cause and nonrecurrence/nonexternal -cause late mortality. ConclusionWhile overall patterns of mortality from other health conditions do not differ over time, adjustment for demographic characteristics provides evidence that risk of treatment-related mortality may be lower in more recent eras. Disparities in health care utilization among survivors should be explored.

SUMMARY Background Positive health-related behaviors are essential for the future wellbeing of childhood cancer survivors, though relatively few maintain healthy behaviors into adulthood. Methods Neurocognitive function and emotional distress were examined in 6,440 adult survivors from the Childhood Cancer Survivor Study, and used to predict rates of expected health-related behaviors. Covariates included cancer diagnosis, age, sex, body mass index, insurance status, income, and antidepressant medication use, and multivariable models were constructed adjusting for these factors. Findings In multivariable regression models, survivors with neurocognitive problems in task efficiency (RR=0.77, 95% CI=0.72–0.84) were less likely to meet the Centers for Disease Control guidelines for weekly physical activity. Survivors with neurocognitive impairment were more likely to engage in general survivor care (RR=1.20, 95% CI=1.10–1.30), and less likely to engage in dental care (RR=0.92, 95% CI=0.88–0.97). Obese survivors were less likely to report receiving a bone density exam (RR=0.67, 95% CI=0.54–0.82), a mammogram (RR=0.71, 95% CI=0.57–0.89), and a skin exam (RR=0.78, 95% CI = 0.68–0.89). Survivors reporting somatization, i.e. vague physical symptoms associated with anxiety, were more likely to report receiving echocardiograms (RR=1.53, 95% CI = 1.32–1.77). Interpretation These results support the link between neurocognitive and emotional problems and health-related behaviors in adult survivors of childhood cancer. Monitoring neurocognitive and emotional outcomes may help to identify survivors at risk for poor adherence to prescribed health behaviors and health screening exams.

The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications.

The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved‐field radiotherapy (IF‐RT) for treating LM from solid tumors with adverse prognostic factors. Fifty‐nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5–15 mg and dexamethasone 5 mg, weekly) and IF‐RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1–3 times) was given before concurrent therapy. Thirty‐eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n = 42), breast cancer (n = 11) and others (n = 6). Median KPS score was 40 (range 20–70). Fifty‐one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1‐year‐survival rate was 21.3%. Treatment‐related adverse events mainly included acute meningitis, chronic‐delayed encephalopathy, radiculitis, myelosuppression and mucositis. Twelve patients (20.3%) had grade III–V toxic reactions. We concluded that IC combined with concomitant IF‐RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. LM, in which cancer cells spread to membranes enveloping the brain and spinal cord, is a devastating complication of solid cancers. Existing LM therapies center on IC. In this prospective clinical study, the authors combined intrathecal methotrexate with involved‐field radiotherapy in a concomitant regimen, showing that the approach can potentially improve quality of life for patients with adverse prognostic factors. Concurrent radiotherapy‐bolstered IC by contributing to prolonged remission of neurological symptoms and increasing OS. The findings suggest that the concomitant regimen could be an optimal treatment option for LM.

In this study, we examined the characteristics and aimed to increase the knowledge of clinical features of leptomeningeal metastasis (LM). The clinical data, including initial diagnosis and treatment of primary tumor, clinical manifestations, neuroimaging findings, cerebrospinal fluid (CSF) examination, were analyzed. For the patients with adenocarcinoma/breast cancer, the incidence of cranial lesions and cranial nerve paralysis was obviously higher than patients with small cell lung cancer. Whereas, the incidence of involvement of intravertebral canal was obviously lower than that of small cell lung cancer. Patients with adenocarcinoma/breast cancer showed more incidence of leptomeningeal enhancement compared to those with small cell lung cancer. Persistent severe headache was noticed in those with squamous carcinoma, and usually showed absence of abnormally LM-related neuroimaging and CSF cytological findings, which resulted in a challenge in the diagnosis of LM from squamous carcinoma. Patients with different primary tumors showed differential clinical features. Significant differences were observed in clinical features between patients with adenocarcinoma/breast cancer and small cell lung cancer. Our study contributes to the understanding of clinical characteristics of LM, and contributes to improvement of LM diagnosis in clinical practice.

Background We aimed to develop and validate a nomogram for predicting the disease-specific survival of Ewing sarcoma (ES) patients. Methods The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify ES from 1990 to 2015, in which the data was extracted from 18 registries in the US. Multivariate analysis performed using Cox proportional hazards regression models was performed on the training set to identify independent prognostic factors and construct a nomogram for the prediction of the 3-, 5-, and 10-year survival rates of patients with ES. The predictive values were compared by using concordance indexes (C-indexes), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Results A total of 2,643 patients were identified. After multivariate Cox regression, a nomogram was established based on a new model containing the predictive variables of age, race, extent of disease, tumor size, and therapy of surgery. The new model provided better C-indexes (0.684 and 0.704 in the training and validation cohorts, respectively) than the model without therapy of surgery (0.661 and 0.668 in the training and validation cohorts, respectively). The good discrimination and calibration of the nomogram were demonstrated for both the training and validation cohorts. NRI and IDI were also improved. Finally, DCA demonstrated that the nomogram was clinically useful. Conclusion We developed a reliable nomogram for determining the prognosis and treatment outcomes of patients with ES in the US. However, the proposed nomogram still requires external data verification in future applications, especially for regions outside the US.

This study aimed to establish a comprehensive prognostic system for osteosarcoma based on a large population database with high quality. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients with osteosarcoma from 1973 to 2015. Multivariate analysis was performed to screen statistically significant variables. A nomogram was constructed by R software to predict the 3-, 5- and 10-year survival rates. Predictive abilities were compared by C-indexes, calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), as well as decision curve analysis (DCA). In total, 4505 osteosarcoma patients were identified. They were divided into training (70%, n = 3153) and validating (30%, n = 1352) groups. Multivariate analyses identified independent predictors. Subsequently, the nomogram system of a new model was established, which comprised 7 variables as age, sex, site, decade of diagnosis (DOD), extent of disease (EOD), tumor size and patients undergoing tri-modality therapy (surgery, radiotherapy and chemotherapy). It provided better C-indexes than the model without therapies (0.727, 0.712 vs 0.705, 0.668) in the 2 cohort, respectively. As well, the new model had good performances in the calibration plots. Moreover, both IDI and NRI improved for 3-, 5- and 10-year follow-up of C-indexes. Finally, DCA demonstrated that the nomogram of new model was clinically meaningful. We developed a reliable nomogram for prognostic determinants and treatment outcome analysis of osteosarcoma, thus helping better choose medical examinations and optimize therapeutic regimen under the cooperation among oncologists and surgeons.

The use of traditional American Joint Committee on Cancer (AJCC) staging alone has limitations in predicting patient survival with nodular melanoma (NM). We aimed to establish a comprehensive prognostic nomogram and compare its prognostic value with the AJCC staging system. A nomogram was constructed to predict the 3-year and 5-year survival rates of NM patients by Cox regression. Several common model-validation parameters were used to evaluate the performance of our survival model. The multivariate analyses demonstrated that the age at diagnosis; being divorced, separated, or widowed; AJCC stages II, III, and IV; a regional SEER stage and the lymph-node density (LND) were risk factors for survival. The concordance index, the area under the time-dependent receiver operating characteristic curve, and calibration plots indicated that the nomogram performed well, while the net reclassification improvement and the integrated discrimination improvement showed that the nomogram performed better than the AJCC staging system. Finally, the decision curve analyses curves of the nomogram yielded net benefits that were higher than when using AJCC staging system with either the training or the validation cohort. The prognostic value of the nomogram is better than that of the AJCC staging system alone. In addition, we found that LND is an important risk factor for the survival of NM patients. The nomogram developed in this study may be a valuable tool for clinical practice when advising patients about their survival risk over the next 3 to 5 years.