Jigisha P. Thakkar

Epidemiologic and Molecular Prognostic Review of Glioblastoma

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system malignancy with a median survival of 15 months. The average incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis is 64 years. Incidence is higher in men and individuals of white race and non-Hispanic ethnicity. Many genetic and environmental factors have been studied in GBM, but the majority are sporadic, and no risk factor accounting for a large proportion of GBMs has been identified. However, several favorable clinical prognostic factors are identified, including younger age at diagnosis, cerebellar location, high performance status, and maximal tumor resection. GBMs comprise of primary and secondary subtypes, which evolve through different genetic pathways, affect patients at different ages, and have differences in outcomes. We report the current epidemiology of GBM with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival. We also provide a concise review on molecular markers in GBM that have helped distinguish biologically similar subtypes of GBM and have prognostic and predictive value. Cancer Epidemiol Biomarkers Prev; 23(10); 1985–96. ©2014 AACR.

A Review of an Unfavorable Subset of Breast Cancer: Estrogen Receptor Positive Progesterone Receptor Negative

Estrogen receptor (ER)(+) progesterone receptor (PR)(-) tumors are a distinct subset of breast cancers characterized by aggressive behavior and tamoxifen resistance in spite of being ER(+). They are categorized as luminal B tumors and have greater genomic instability and a higher proliferation rate. High growth factor (GF) signaling and membranous ER activity contribute to the aggressive behavior of these tumors. The absence of PR is attributable to low serum estrogen, low levels of nuclear ER, and features of molecular crosstalk between GFs and membranous ER. PR expression is also downregulated by expression of mutated epidermal growth factor receptor (EGFRvIII). This subset of patients has greater expression of human epidermal growth factor receptor (HER)-1 and HER-2 and active GF signaling mediated by the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway. Currently, aromatase inhibitors, fulvestrant, and chemotherapy may be the favored treatment approaches for this subset of patients. Overcoming tamoxifen resistance with targeted therapies such as gefitinib is being evaluated and strategies involving short courses of tamoxifen have been postulated for prevention of recurrence of this subtype. Understanding the interplay between molecular endocrinology and tumor biology has provided experimental therapeutic insights, and continued work in this area holds the promise of future advances in prognosis.

Epidemiology of meningiomas post‐Public Law 107‐206: The Benign Brain Tumor Cancer Registries Amendment Act

The current analysis follows the implementation of Public Law 107‐260, the Benign Brain Tumor Cancer Registries Amendment Act, which mandated the collection of nonmalignant brain tumors.

Incidence of brain metastasis at initial presentation of lung cancer

BACKGROUND No reliable estimates are available on the incidence of brain metastasis (BM) in cancer patients. This information is valuable for planning patient care and developing measures that may prevent or decrease the likelihood of metastatic brain disease. METHODS We report the first population-based analysis on BM incidence at cancer diagnosis using the Kentucky Cancer Registry (KCR) and Alberta Cancer Registry (ACR). All cancer cases with BM were identified from KCR and ACR, with subsequent focus on metastases from lung primaries; the annual number of BMs at initial presentation was derived. Comparisons were made between Kentucky and Alberta for the stage and site of organ involvement of lung cancer. RESULTS Low incidence of BM was observed in the United States until mandatory reporting began in 2010. Both the KCR and ACR recorded the highest incidence of BM from lung cancer, with total BM cases at initial presentation occurring at 88% and 77%, respectively. For lung cancer, stage IV was the most common stage at presentation for both registries and ranged from 45.9% to 57.2%. When BM from lung was identified, the most common synchronous organ site of metastasis was osseous, occurring at 28.4%. CONCLUSION Our analysis from the Kentucky and Alberta cancer registries similarly demonstrated the aggressive nature of lung cancer and its propensity for BM at initial presentation. Besides widespread organ involvement, no synchronous organ site predicted BM in lung cancer. BM is a common and important clinical outcome, and use of registry data is becoming more available.

Age-Specific Cancer Incidence Rates Increase Through the Oldest Age Groups

Background:In the United States, from 2005 to 2009, nearly 8% of all cancers diagnosed and 15% of cancer deaths occurred in individuals aged 85 years and older (85+ age group). With the aging of the U.S. population, an analysis of incidence of cancer in the elderly population may provide information for clinical care and resource allocation. Materials and Methods:Previously reported data were retrieved from the Surveillance Epidemiology and End Results (SEER) 18 Registry for years 2000 to 2010 and Central Brain Tumor Registry of the United States (CBTRUS) for years 2004 to 2008. Cancers included invasive cases only, except for nonmalignant meningiomas, and rates were per 100,000. Results:The age-specific cancer incidence rate (IR) increases with age until a decrease in the 85+ age group. IR for all cancers combined for this age group was 2,317 per 100,000. Statistically, males had significantly higher IR compared with females (3,194 versus 1,911 [P ⩽ 0.0001]). Blacks had an IR similar to whites (2,255 versus 2,340 [P = 0.12]). Despite a drop in the overall IR in this oldest age group, IR for certain cancers continued to increase. Among these cancers, gastrointestinal cancers like colorectal, pancreatic and stomach had the highest incidence and mortality rates. Conclusions:This study contributes to measuring cancer burden in the oldest old population. In certain cancers, including meningiomas, the IR continues to rise with advancing age. Management of cancer in elderly is challenging and screening persons in the 85+ age group for frailty very thoroughly may help guide decisions of palliative versus aggressive therapies.

Clinical InvestigationAge-Specific Cancer Incidence Rates Increase Through the Oldest Age Groups

Background:In the United States, from 2005 to 2009, nearly 8% of all cancers diagnosed and 15% of cancer deaths occurred in individuals aged 85 years and older (85+ age group). With the aging of the U.S. population, an analysis of incidence of cancer in the elderly population may provide information for clinical care and resource allocation. Materials and Methods:Previously reported data were retrieved from the Surveillance Epidemiology and End Results (SEER) 18 Registry for years 2000 to 2010 and Central Brain Tumor Registry of the United States (CBTRUS) for years 2004 to 2008. Cancers included invasive cases only, except for nonmalignant meningiomas, and rates were per 100,000. Results:The age-specific cancer incidence rate (IR) increases with age until a decrease in the 85+ age group. IR for all cancers combined for this age group was 2,317 per 100,000. Statistically, males had significantly higher IR compared with females (3,194 versus 1,911 [P ⩽ 0.0001]). Blacks had an IR similar to whites (2,255 versus 2,340 [P = 0.12]). Despite a drop in the overall IR in this oldest age group, IR for certain cancers continued to increase. Among these cancers, gastrointestinal cancers like colorectal, pancreatic and stomach had the highest incidence and mortality rates. Conclusions:This study contributes to measuring cancer burden in the oldest old population. In certain cancers, including meningiomas, the IR continues to rise with advancing age. Management of cancer in elderly is challenging and screening persons in the 85+ age group for frailty very thoroughly may help guide decisions of palliative versus aggressive therapies.

Intra-CSF administration of chemotherapy medications

Leptomeningeal carcinomatosis is a devastating complication of cancer and is likely increasing in incidence. The combination of widespread neuro-axial spread based on CSF flow and the blood–brain barrier (BBB) has favored immediate local delivery of antineoplastic agents. With the BBB, the leptomeninges can be a sanctuary site to systemic cancers and goal of therapy includes preventing involvement in this space. Current therapies with U.S. Food and Drug Administration (FDA) approval are limited to treat hematologic cancers. Although lacking FDA guidance, a wider array of therapies is available to treat solid tumors. We provide an updated examination on both well-established intra-CSF chemotherapies as well as agents having limited data, but reports of therapeutic benefit.

National cancer database analysis of outcomes in pediatric glioblastoma

Glioblastoma in children is an aggressive disease with no defined standard therapy. We evaluated hospital‐based demographic and survival patterns obtained through the National Cancer Database to better characterize children with glioblastoma. Our study identified 1173 patients from 0 to 19 years of age between 1998 and 2011. Comparisons were made among demographics, clinical characteristics, treatment, and survival variables. Fifty‐four percent of patients were over 10 years of age. Approximately 80% of patients underwent either partial or complete resection. Adjuvant therapy was used variably, and its use increased with patient age. Forty‐eight percent of patients received the combination of surgery, radiation, and chemotherapy, and 4% did not receive any treatment. As expected, patients ≤5 years of age had better 5‐year survival than those ages 6–10 (P = 0.01) or 11–19 years (P = 0.0077). Other factors associated with poor survival included black race and central tumor location. Better outcomes were associated with treatment that included surgery, radiotherapy, and chemotherapy compared to any other treatment combinations. Radiotherapy had no impact on survival in the 0 to 10‐year‐old age group, but was associated with improved survival for patients 11–19 years. We report an extensive demographic and survival analysis of pediatric glioblastoma. The observed differences likely reflect variances in tumor biology and likelihood of treatment receipt. Improved survival was associated with the use of surgery, radiotherapy, and chemotherapy. Radiation therapy was not associated with survival in patients younger than 10 years of age.

Inguinal lymph node metastasis of colon cancer.

We present a case of adenocarcinoma of colon with unusual metastasis to inguinal lymph nodes. Our patient is a young male with bilateral inguinal lymphadenopathy, bone pains, and jaundice who presented as carcinoma of unknown primary. He was diagnosed as widely metastatic adenocarcinoma of colon for which he received chemotherapy and has had a good response to the treatment.

Bilateral Radiation Optic Neuropathy Following Concurrent Chemotherapy and Radiation in Glioblastoma

ABSTRACT Radiation optic neuropathy (RON) is an iatrogenic complication that causes severe, irreversible vision loss within months to years following radiation to lesions close to the visual pathway. The authors describe a case of RON in glioblastoma after radio-sensitisation with temozolomide with sequential involvement of both optic nerves. This case provides a timeline for clinical and imaging findings with RON and specifically resolution of nerve enhancement. The authors also highlight the potential of an increase in incidence of RON in glioblastoma with advances in survival seen with greater use of second-line chemotherapy and even re-radiation.