Ayal A. Aizer

Marital Status and Survival in Patients With Cancer

PURPOSE To examine the impact of marital status on stage at diagnosis, use of definitive therapy, and cancer-specific mortality among each of the 10 leading causes of cancer-related death in the United States. METHODS We used the Surveillance, Epidemiology and End Results program to identify 1,260,898 patients diagnosed in 2004 through 2008 with lung, colorectal, breast, pancreatic, prostate, liver/intrahepatic bile duct, non-Hodgkin lymphoma, head/neck, ovarian, or esophageal cancer. We used multivariable logistic and Cox regression to analyze the 734,889 patients who had clinical and follow-up information available. RESULTS Married patients were less likely to present with metastatic disease (adjusted odds ratio [OR], 0.83; 95% CI, 0.82 to 0.84; P < .001), more likely to receive definitive therapy (adjusted OR, 1.53; 95% CI, 1.51 to 1.56; P < .001), and less likely to die as a result of their cancer after adjusting for demographics, stage, and treatment (adjusted hazard ratio, 0.80; 95% CI, 0.79 to 0.81; P < .001) than unmarried patients. These associations remained significant when each individual cancer was analyzed (P < .05 for all end points for each malignancy). The benefit associated with marriage was greater in males than females for all outcome measures analyzed (P < .001 in all cases). For prostate, breast, colorectal, esophageal, and head/neck cancers, the survival benefit associated with marriage was larger than the published survival benefit of chemotherapy. CONCLUSION Even after adjusting for known confounders, unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer. This study highlights the potentially significant impact that social support can have on cancer detection, treatment, and survival.

Multidisciplinary Care and Pursuit of Active Surveillance in Low-Risk Prostate Cancer

PURPOSE Multidisciplinary clinics offer a unique approach to the management of patients with cancer. Yet, limited data exist to show that such clinics affect management. The purpose of this study was to determine whether consultation at a multidisciplinary clinic is associated with selection of active surveillance in patients with low-risk prostate cancer. PATIENTS AND METHODS The study comprised 701 men with low-risk prostate cancer managed at three tertiary care centers in Boston, MA in 2009. Patients either obtained consultation at a multidisciplinary prostate cancer clinic, at which they were seen by a combination of urologic, radiation, and medical oncologists in a concurrent setting, or they were seen by individual practitioners in sequential settings. The primary outcome was selection of active surveillance. RESULTS Crude rates of selection of active surveillance in patients seen at a multidisciplinary clinic were double that of patients seen by individual practitioners (43% v 22%), whereas the proportion of men treated with prostatectomy or radiation decreased by approximately 30% (P < .001). On multivariate logistic regression, older age (odds ratio [OR], 1.09; 95% CI, 1.05 to 1.12; P < .001), unmarried status (OR, 1.66; 95% CI, 1.01 to 2.72; P = .04), increased Charlson comorbidity index (OR, 1.37; 95% CI, 1.06 to 1.77; P = .02), fewer positive cores (OR, 0.92; 95% CI, 0.90 to 0.94; P < .001), and consultation at a multidisciplinary clinic (OR, 2.15; 95% CI, 1.13 to 4.10; P = .02) were significantly associated with pursuit of active surveillance. CONCLUSION Multidisciplinary care is associated with increased selection of active surveillance in men with low-risk prostate cancer. This finding may have an important clinical, social, and economic impact.

Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair

While axonal regeneration is more successful in peripheral nerve than in the central nervous system, it is by no means complete and research to enhance peripheral nerve regeneration is clinically important. Olfactory ensheathing cells (OECs) are known to enhance axonal regeneration and to produce myelin after transplantation. In contrast to Schwann cells their migratory potential and ability to penetrate glial scars is higher. This study evaluated the effect of OEC transplantation on microsurgically repaired sciatic nerves. Rat sciatic nerves were transected followed by microsurgical repair and transplantation of OECs or injection of medium without cells. Twenty-one days later the nerves were removed and prepared for either histology or electrophysiological analysis. Footprint analysis was carried out at 7, 14 and 21 days. The OECs survived and integrated into the repaired nerves as indicated by eGFP-expressing cells aligned with neurofilament identified axons bridging the repair site. Moreover, regenerated axons were myelinated by the transplanted OECs and nodes of Ranvier were formed. Conduction velocity in the OEC transplant group was increased in comparison to the microsurgical repair alone, and improved stepping was observed in the transplant group. These results suggest that presentation of OECs at the time of nerve injury enhances regeneration and improves functional outcome. Even a modest improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

Cancer-Specific Outcomes Among Young Adults Without Health Insurance

PURPOSE The Patient Protection and Affordable Care Act (ACA) will likely improve insurance coverage for most young adults, but subsets of young adults in the United States will face significant premium increases in the individual market. We examined the association between insurance status and cancer-specific outcomes among young adults. METHODS We used the SEER program to identify 39,447 patients age 20 to 40 years diagnosed with a malignant neoplasm between 2007 and 2009. The association between insurance status and stage at presentation, employment of definitive therapy, and all-cause mortality was assessed using multivariable logistic or Cox regression, as appropriate. RESULTS Patients who were uninsured were more likely to be younger, male, nonwhite, and unmarried than patients who were insured and were also more likely to be from regions of lower income, education, and population density (P < .001 in all cases). After adjustment for pertinent confounding variables, an association between insurance coverage and decreased likelihood of presentation with metastatic disease (odds ratio [OR], 0.84; 95% CI, 0.75 to 0.94; P = .003), increased receipt of definitive treatment (OR, 1.95; 95% CI, 1.52 to 2.50; P < .001), and decreased death resulting from any cause (hazard ratio, 0.77; 95% CI, 0.65 to 0.91; P = .002) was noted. CONCLUSION The improved coverage fostered by the ACA may translate into better outcomes among most young adults with cancer. Extra consideration will need to be given to ensure that patients who will face premium increases in the individual market can obtain insurance coverage under the ACA.

Whole Pelvic Radiotherapy Versus Prostate Only Radiotherapy in the Management of Locally Advanced or Aggressive Prostate Adenocarcinoma

PURPOSE To determine whether whole pelvic radiotherapy (WPRT) or prostate-only radiotherapy (PORT) yields improved biochemical disease-free survival (BDFS) in patients with advanced or aggressive prostate adenocarcinoma. METHODS AND MATERIALS Between 2000 and 2007, a consecutive sample of 277 patients with prostate adenocarcinoma and at least a 15% likelihood of lymph node involvement who had undergone WPRT (n = 68) or PORT (n = 209) at two referral centers was analyzed. The median radiation dose in both arms was 75.6 Gy. The outcome measure was BDFS, as determined using the prostate-specific antigen nadir + 2 ng/mL definition of failure. BDFS was calculated using the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed to assess for confounding. Treatment-related toxicity was assessed using the National Cancer Institutes Common Terminology Criteria for Adverse Events guidelines. The median follow-up was 30 months. RESULTS WPRT patients had more advanced and aggressive disease at baseline (p < .001). The 4-year BDFS rate was 69.4% in the PORT cohort and 86.3% in the WPRT cohort (p = .02). Within the entire cohort, after adjustment for confounding variables, the pretreatment prostate-specific antigen (p < .001), Gleason score (p < .001), use of hormonal therapy (p = .002), and use of WPRT (vs. PORT, p = .006) predicted for BDFS. Patients undergoing WPRT had increased acute gastrointestinal toxicity (p = .048), but no significant difference in acute genitourinary toxicity was seen (p = .09). No difference in late toxicity was found. CONCLUSION WPRT may yield improved BDFS in patients with advanced or aggressive prostate adenocarcinoma, but results in a greater incidence of acute toxicity.

Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma

BACKGROUND Meningiomas are the most common primary intracranial tumor in adults. Identification of SMO and AKT1 mutations in meningiomas has raised the possibility of targeted therapies for some patients. The frequency of such mutations in clinical cohorts and the presence of other actionable mutations in meningiomas are important to define. METHODS We used high-resolution array-comparative genomic hybridization to prospectively characterize copy-number changes in 150 meningiomas and then characterized these samples for mutations in AKT1, KLF4, NF2, PIK3CA, SMO, and TRAF7. RESULTS Similar to prior reports, we identified AKT1 and SMO mutations in a subset of non-NF2-mutant meningiomas (ie, ∼9% and ∼6%, respectively). Notably, we detected oncogenic mutations in PIK3CA in ∼7% of non-NF2-mutant meningiomas. AKT1, SMO, and PIK3CA mutations were mutually exclusive. AKT1, KLF4, and PIK3CA mutations often co-occurred with mutations in TRAF7. PIK3CA-mutant meningiomas showed limited chromosomal instability and were enriched in the skull base. CONCLUSION This work identifies PI3K signaling as an important target for precision medicine trials in meningioma patients.

Marital status and head and neck cancer outcomes

The objective of this study was to examine the effects of marital status on stage at presentation, receipt of treatment, and survival in patients with head and neck cancer (HNC).

Glioproliferative Lesion of the Spinal Cord as a Complication of “Stem-Cell Tourism”

A primitive neoplasm composed predominantly of nonhost cells was detected in the thoracic spinal cord and thecal sac of a 66-year-old man who had received experimental stem-cell treatment from commercial clinics.

Radical prostatectomy vs. intensity-modulated radiation therapy in the management of localized prostate adenocarcinoma

BACKGROUND AND PURPOSE To determine whether radical prostatectomy (RP) or intensity-modulated radiation therapy (IMRT) to > or =72 Gy, plus hormonal therapy if indicated, results in improved biochemical disease-free survival (BDFS) in localized prostate adenocarcinoma. MATERIALS AND METHODS Between 1997 and 2005, a consecutive sample of 556 patients who underwent RP (n=204) or IMRT (n=352) at two referral centers was analyzed. The patients were stratified into prognostic groups based on clinical stage, Gleason score, and pretreatment prostate-specific antigen (PSA). The outcome measure was BDFS. RESULTS IMRT patients had more advanced disease at baseline (p<.001). There was no difference in five-year BDFS rates between RP and IMRT in the favorable (92.8% vs. 85.3%, p=.20) or intermediate prognosis (86.7% vs. 82.2%, p=.46) subsets. A difference favoring IMRT plus hormonal therapy was seen in the poor prognosis (38.4% vs. 62.2%, p<.001) subset. Within the entire cohort, after adjustment for confounding variables, Gleason score (p<.001) and clinical stage (p<.001) predicted BDFS, but treatment modality (p=.06) did not. Within the poor prognosis subset, treatment modality (p=.006) predicted BDFS. CONCLUSIONS BDFS is similar between RP and IMRT for patients with a favorable or intermediate prognosis. Patients with a poor prognosis display higher BDFS when treated with IMRT to > or =72 Gy plus hormonal therapy.

Extent of resection and overall survival for patients with atypical and malignant meningioma

The prognosis for patients with atypical and malignant meningioma is guarded; whether the extent of resection is associated with survival‐based outcomes in this population remains poorly defined. This study investigated the association between gross total resection (GTR) and all‐cause mortality in patients with atypical and malignant meningioma.