Benign and malignant pulmonary parenchymal findings on chest CT among adult survivors of childhood and young adult cancer with a history of chest radiotherapy.

PURPOSE: Childhood and young adult cancer survivors exposed to chest radiotherapy are at increased risk of lung cancer. In other high-risk populations, lung cancer screening has been recommended. Data is lacking on prevalence of benign and malignant pulmonary parenchymal abnormalities in this population. METHODS: We conducted a retrospective review of pulmonary parenchymal abnormalities in chest CTs performed more than 5 years post-cancer diagnosis in survivors of childhood, adolescent, and young adult cancer. We included survivors exposed to radiotherapy involving the lung field and followed at a high-risk survivorship clinic between November 2005 and May 2016. Treatment exposures and clinical outcomes were abstracted from medical records. Risk factors for chest CT-detected pulmonary nodule were assessed. RESULTS: Five hundred and ninety survivors were included in this analysis: median age at diagnosis, 17.1 years (range, 0.4-39.8); and median time since diagnosis, 22.3 years (range, 1-58.6). At least one chest CT more than 5 years post-diagnosis was performed in 338 survivors (57%). Among these, 193 (57.1%) survivors had at least one pulmonary nodule detected on a total of 1057 chest CTs, resulting in 305 CTs with 448 unique nodules. Follow-up was available for 435 of these nodules; 19 (4.3%) were malignant. Risk factors for first pulmonary nodule were older age at time of CT, CT performed more recently, and splenectomy. CONCLUSIONS: Benign pulmonary nodules are very common among long-term survivors of childhood and young adult cancer. IMPLICATIONS FOR CANCER SURVIVORS: High prevalence of benign pulmonary nodules in cancer survivors exposed to radiotherapy could inform future guidelines on lung cancer screening in this population.

Benign and Malignant Findings on Chest CT Among Adult Survivors of Childhood and Young Adult Cancer with a History of Chest Radiotherapy.

Purpose : Childhood and young adult cancer survivors exposed to chest radiotherapy are at increased risk of lung cancer. In other high-risk populations, lung cancer screening has been recommended. Data is lacking on prevalence of benign and malignant imaging abnormalities in this population. Methods : We conducted a retrospective review of imaging abnormalities in chest CTs performed more than 5 years post-cancer diagnosis in survivors of childhood, adolescent, and young adult cancer. We included survivors exposed to radiotherapy involving the lung field and followed at a high-risk survivorship clinic between November 2005 and May 2016. Treatment exposures and clinical outcomes were abstracted from medical records. Risk factors for chest CT-detected pulmonary nodule were assessed. Results : Five hundred and ninety survivors were included in this analysis; median age at diagnosis, 17.1 years (range, 0.4-39.8) and median time since diagnosis, 21.1 years (range, 0.4-58.6). At least one chest CT more than 5 years post-diagnosis was performed in 338 survivors (57%). Among these, 193 (57.1%) survivors had at least one pulmonary nodule detected on a total of 1057 chest CTs, resulting in 305 CTs with 448 unique nodules. Follow-up was available for 435 of these nodules; 19 (4.3%) were malignant. Risk factors for first pulmonary nodule were older age at time of CT, CT performed more recently and splenectomy. Conclusions : Benign pulmonary nodules are very common among long-term survivors of childhood and young adult cancer. Implications for Cancer Survivors: High prevalence of benign pulmonary nodules in cancer survivors exposed to radiotherapy could inform future guidelines on lung cancer screening in this population.

The Association of Post-Concussion and Post-Traumatic Stress Disorder Symptoms with Health-Related Quality of Life, Health Care Use and Return-to-Work after Mild Traumatic Brain Injury.

Patients with mild traumatic brain injury (mTBI) are at risk for post-concussion (PC) symptoms and post-traumatic stress disorder (PTSD). The co-occurrence of PC and PTSD symptoms after mTBI in relation to health-related quality of life (HRQoL), health care utilization, and return to work has not yet been investigated. PC and PTSD symptoms were measured six months post-TBI by respectively the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). Of the 1566 individuals after mTBI who met the inclusion criteria, 26.1% experienced PC symptoms (RPQ ≥16). Additionally, 9.8% experienced PTSD symptoms (PCL-5 ≥ 33), of which the vast majority (81%) also reported experiencing PC symptoms. Differences between patients with no/mild symptoms, with only PC, only PTSD, and both PC and PTSD symptoms in HRQoL, return to work, and rehabilitation were analyzed using logistic and linear regression analyses. Patients with PC and/or PTSD symptoms reported lower HRQoL, higher rates of rehabilitation, and lower return to work rates compared to patients with no/mild symptoms. Patients with both PC and PTSD symptoms reported significantly lower HRQoL (B = -2.73, CI = -4.65; -0.83, p < 0.001) compared to those with only PC symptoms, while there were no significant differences in their ongoing rehabilitation care (OR = 1.39, CI = 0.77-2.49, p = 0.272) and return to work rates (OR = 0.49, CI = 0.15-1.63, p = 0.246) at six months. These results underline the importance of the diagnosis and appropriate treatment of patients with mTBI, experiencing PC and/or PTSD symptoms.

Renal and pulmonary late effects of cancer therapy.

Both the kidneys and lungs are susceptible to the toxic effects of cancer therapy, with specific chemotherapy agents, as well as radiation therapy, leading to acute toxicities and the risk for long-term dysfunction. The kidneys also are vulnerable to the direct impact of the cancer itself and to supportive care drugs such as certain anti-infectives and immunosuppressive agents, nonsteroidal anti-inflammatories, and radiocontrast media. The lungs are especially vulnerable after hematopoietic stem cell transplantation (HSCT), particularly in patients who develop chronic graft-versus-host disease. This article will discuss the epidemiology, specific risk factors, pathogenesis, natural history, recommended screening, preventive strategies, treatment, and areas for future research into renal and pulmonary toxicity in survivors of cancer.

Phase II study of everolimus in metastatic urothelial cancer.

UNLABELLED: What's known on the subject? and what does the study add?: No recent advances have been made in the treatment of patients with advanced bladder cancer and, to date, targeted therapies have not resulted in an improvement in outcome. The mammalian target of rapamycin pathway has been shown to be up-regulated in bladder cancer and represents a rational target for therapeutic intervention. In the present phase II study of everolimus, one near-complete response, one partial response and several minor responses suggest that everolimus possesses biological activity in a subset of patients with bladder cancer. To maximize benefit from targeted agents such as everolimus, the preselection of patients based on molecular phenotype is required. OBJECTIVE: To assess the efficacy and tolerability of everolimus in advanced urothelial carcimoma (UC). PATIENTS AND METHODS: The present study comprised a single-arm, non-randomized study in which all patients received everolimus 10 mg orally once daily continuously (one cycle = 4 weeks). In total, 45 patients with metastatic UC progressing after one to four cytotoxic agents were enrolled between February 2009 and November 2010 at the Memorial Sloan-Kettering Cancer Center. The primary endpoints were 2-month progression-free survival (PFS) and the safety of everolimus, with the secondary endpoint being the response rate. A Simon minimax two-stage design tested the null hypothesis that the true two month PFS rate was ≤ 50%, as opposed to the alternative hypothesis of ≥ 70%. RESULTS: The most common grade 3/4 toxicities were fatigue, infection, anaemia, lymphopaenia, hyperglycaemia and hypophosphataemia. There were two partial responses in nodal metastases, with one patient achieving a 94% decrease in target lesions and remaining on drug at 26 months. An additional 12 patients exhibited minor tumour regression. There were 23 of 45 (51%) patients who were progression-free at 2 months with a median (95% CI) PFS of 2.6 (1.8-3.5) months and a median (95% CI) overall survival of 8.3 (5.5-12.1) months. No clear association was observed between mammalian target of rapamycin pathway marker expression and 2-month PFS. CONCLUSIONS: Although everolimus did not meet its primary endpoint, one partial response, one near-complete response and twelve minor regressions were observed. Everolimus possesses meaningful anti-tumour activity in a subset of patients with advanced UC. Studies aiming to define the genetic basis of everolimus activity in individual responders are ongoing.

Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers.

H19, a paternally imprinted gene, is postulated to have regulatory functions in normal development and oncogenesis. Loss of imprinting (LOI) of H19 is observed in human malignancies, including lung cancer. Microarray assessment of gene expression patterns in airway epithelium of healthy 20 pack-year smokers versus nonsmokers revealed that smokers have dramatically elevated H19 RNA levels without alteration of expression of other imprinted genes. Interestingly, the up-regulation of H19 was not attributable to LOI, i.e., expression of H19 in smokers was monoallelic. These observations suggest that cigarette smoking initially induces up-regulation of the active H19 allele and that there is likely progression to LOI as the burden of smoking increases and as the epithelium undergoes transition from normal to neoplastic. Overexpression and eventual LOI of H19 may represent early markers in the progression of airway epithelium toward lung cancer.

Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers.

Cigarette smoking is the major risk factor for developing chronic bronchitis, yet only 15-20% of smokers develop this disorder. Because oxidants are the major mechanism of smoking-induced airway damage, we hypothesized that smoking is associated with upregulation of various antioxidant-related genes in the airway epithelium, but the magnitude of the response shows high inter-individual variability. Microarray analysis was used to assess levels of expression of 44 antioxidant-related genes in four categories (catalase/superoxide dismutase family; glutathione metabolism; redox balance; and pentose phosphate cycle) in bronchoscopy-obtained airway epithelium of matched cohorts (13 current smokers, 9 nonsmokers), none of whom had lung disease. There was minimal variation in gene expression levels within the same individual (right versus left lung or over time), but significant upregulation of 16/44 antioxidant-related genes in smoker epithelium compared with nonsmokers. Subgroups of smokers were identified with clusters of expression levels of antioxidant-related genes. We propose that the antioxidant-related genes demonstrating the most variability in the level of expression in smokers may be useful genetic markers in epidemiologic studies assessing susceptibility to smoking-induced chronic bronchitis.