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Breast cancer is one of the most common malignancies in women, affecting one in twelve. Ovarian cancer, although not as frequent, is the leading cause of death from gynaecological cancer. Inherited predisposition to breast and ovarian cancer, which accounts for approximately 5 to 10% of these cancers, has been associated with mutations in the BRCA1 and BRCA2 genes. Mutations in both of these genes increase the lifetime risk of developing breast cancer by approximately 80%. BRCA1 confers a greater predisposition of ovarian cancer than BRCA2, however, BRCA2 has been associated with male breast cancer. Polymorphisms linked to BRCA1 and BRCA2 were studied to examine whether either of these genes were linked to breast and breast/ovarian cancer families. None of the five cancer families studied generated statistically significant lod scores although the segregation of a common haplotype with the disease in each family and positive lod scores did suggest that four of these families were linked to BRCA1 and the other to BRCA2. Subsequent mutation studies identified three germline mutations, thus confirming the initial linkage results in three families. A total of four deletions and six polymorphisms were identified in BRCA1 and BRCA2 from forty-eight breast and breast/ovarian cancer families, using SSCP analysis and PTT. The functional effect of these mutations is unclear although variable expression of the cancer phenotype suggests that other genes and environmental factors play an important role in the development of breast and ovarian cancer. Evidence of an abnormal protein was detected by the presence of clonal LOH of the normal allele, using BRCA1 antibodies in familial breast and ovarian tumours. In addition, BRCA1 immunostaining was negative in a greater proportion of benign tumours compared to malignant ovarian tumours. The loss of BRCA1 does not lead to malignancy, suggesting that BRCA1 may have another role in benign ovarian epithelial tumours.

Class of 2017 Abstract / This project is related to the article that was later published, available at this link: https://doi.org/10.1016/j.critrevonc.2016.11.009 / Objectives: Brentuximab vedotin (BV) is an antibody-drug conjugate comprising a CD30-directed antibody conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma and relapsed systemic Methods: primary study outcomes being objective response rate. PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015). Inclusion criteria included all studies and case reports of NHLs in which BV therapy was administered. Twenty-eight articles met these criteria. Results: Utilizing the twelve clinical subtypes, we found clinical evidence of BV and stratified the study populations into three groups: B-cell malignancies (group A), T-cell malignancies (group B), and non-B or non-T-cell hematological malignancies (group C). Across the group A malignancies, there were 87 patients. 48% experienced an objective response (OR). Across the group B malignancies, there were 274 patients. 74% experienced an OR. Across the group C malignancies, there were 9 patients. 44% experienced an OR. Conclusions: Our findings indicate that BV induces a variety of responses, largely positive and variable between NHL subtypes. With properly powered prospective studies, BV may prove to be a strong candidate in the treatment of CD30+ malignancies.

Class of 2012 Abstract / Specific Aims: To evaluate disease- and patient-related characteristics, mortality, and charges associated with non-AIDS defining malignancies (NADM) among inpatient settings in the United States from 2005 to 2009. Methods: This retrospective cohort investigation utilized nationally-representative hospital discharge records from the Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (H-CUP) Nationwide Inpatient Sample. Inclusion criteria included adult inpatients ≥18 years with a diagnosis of HIV or AIDS and malignant neoplasms. Multivariate regression analyses were used to assess inpatient mortality and charges. Main Results: Overall, 104,488 were included. Average age associated with each case was 46.9 years (±10.66), with 21.9% cases being female (n=22,868). The mean length of stay was 8.6 days (±10.5) and inpatient mortality occurred in 7.7% of cases (n=8,035). The mean number of procedures performed was 2.3 (±2.5) and the mean number of diagnoses on record was 9.5 (±4.4). Charges for each episode of care averaged $59,483 (±85,748), summing to a national bill of $6.14 billion (2011 dollars) over the five-year course. A higher number of cases were associated with teaching hospitals (74.1%), the south (42%), large metropolitan areas (75.1%), median household income in the 0-25th percentile (41.2%), and Medicaid payers (34.3%). Increased mortality was associated with increased age, increased number of diagnoses and procedures, and the comorbidities of anemia, coagulopathy, lymphoma, and fluid and electrolyte disorders. Conclusions: This investigation of NADMs suggest a considerable clinical and economic burden of illness, summing to a 7.7% inpatient death rate and $1.3 billion in charges per year.

Thesis (Ph. D.)--Rutgers University, 2010. / "Graduate Program in Public Health." Includes bibliographical references.

Oral cancer is a major health problem, with over 500000 patients diagnosed each year. Although progress has been made in regards to both diagnosis and treatment, the overall 5-year survival rate has not changed much in the last 30 years and still relatively static at around 50 %. This high mortality rate is related to late diagnosis of oral malignancies. At stages III and IV the 5-year survival rate is as low as 30 %, however if diagnosed at stage I the survival rate increases substantially to approximately 80 %. Research in to viable methods for early detection of oral malignancies and potential malignancies has the potential to save lives and reduce suffering for many people word wide. The purpose of this systematic review is to find an effective and practical diagnostic test for early detection of malignancies and potential malignancies in the oral cavity. Electronic database searches were conducted in English on the 4th of February 2017, using PubMed medical database, publication date 2005 or later. Inclusion criteria: Diagnostic Test Accuracy studies for oral malignancies and potential malignancies in human patients with gold standard reference test. Search yielded 166 records, titles and abstracts was screened and evaluated, 19 records was included. Included studies were assessed in detail regarding methodological quality and diagnostic accuracy. 19 studies with a total of 11575 participants were included. The studies were subdivided in to groups based on the specific index test assessed in each study. Diagnostic accuracy results: 4 records assessed Tissue autofluorescence; sensitivity ranging from 65.5 % to 100 % and specificity ranging from 41.7 % to 97.4 %. 10 records assessed Brush biopsy sampling; sensitivity ranging from 45 % to 100 % and specificity ranging from 90 % to 100 %. 1 record assessed Blood sampling; sensitivity 64 % and specificity 80 %. 2 records assessed saliva sampling Saliva sampling; sensitivity 100 % and specificity 96.7 %. 1 record assessed Metachromatic dye staining; detection rate of experimental group was 5 % higher than control group. 1 record assessed Narrow-band imaging; sensitivity 95 % and specificity 97 %. The Brush biopsy sampling diagnostic test methods has a body of evidence that far exceeds any other category presented in this review. As for methodological quality, diagnostic accuracy and risk of bias, we deemed the category as a whole to be at an acceptable level.

PURPOSE:To assess if intensity-modulated radiotherapy (IMRT) can possibly lead to improved local control and lower incidence of vision impairment/blindness in comparison to non-IMRT techniques when treating sinonasal malignancies / what is the most optimal dose constraints for the optic pathway / and the impact of different IMRT strategies on optic pathway sparing in this setting.METHODS AND MATERIALS:A literature search in the PubMed databases was conducted in July, 2012.RESULTS:Clinical studies on IMRT and 2D/3D (2 dimensional/3 dimensional) RT for sinonasal malignancies suggest improved local control and lower incidence of severe vision impairment with IMRT in comparison to non-IMRT techniques. As observed in the non-IMRT studies, blindness due to disease progression may occur despite a lack of severe toxicity possibly due to the difficulty of controlling locally very advanced disease with a dose less than or equal to] 70Gy. Concurrent chemotherapy's influence on the the risk of severe optic toxicity after radiotherapy is unclear. A maximum dose of less than or equal to] 54Gy with conventional fractionation to the optic pathway may decrease the risk of blindness. Increased magnitude of intensity modulation through increasing the number of segments, beams, and using a combination of coplanar and non-coplanar arrangements may help increase dose conformality and optic pathway sparing when IMRT is used.CONCLUSION:IMRT optimized with appropriate strategies may be the treatment of choice for the most optimal local control and optic pathway sparing when treating sinonasal malignancy.