Family medical history from previous generations often goes unpreserved, and critical records either lost or discarded. Historically, cancer survivors received information in a Survivorship Care Plan (SCP). However, SCPs are not always provided; when they are, usefulness varies when pieces are missing, such as genetic test results and updated family history. Certain medical records after a cancer diagnosis should be saved as they allow other providers to accurately assess cancer risk and provide appropriate screening recommendations for individuals with cancer and their family members. Participants viewed a 5-minute educational, animated video (available in English and Spanish) that included an acronym checklist (GROUPS/GRUPOS) to teach which medical documents should be collected after a cancer diagnosis, why they are important to keep, and how to save them for subsequent generations. Identical questions were asked before and after the video to measure knowledge gained from the educational tool. Statistically significant results were observed for the difference between the overall pre and post scores (p<0.001), all four domains: knowledge of medical records to keep after a cancer diagnosis, how to locate these records, awareness of the importance to save them, and confidence in saving them (p<0.001), and 14 of 16 individual survey questions (p≤0.001). Data showed improvements in “Knowledge that saving medical records is helpful” (p=0.006) and “Knowledge of ‘S’” (Surgical histories) in the list of GROUPS records (p=0.002), but statistical significance was not observed for these pre and post score differences. Two categorical variables were statistically significant: sex for knowing “R” (Relatives with cancer) (p<0.001); females knew more than men about their relatives with cancer and age at time of survey for overall score (p=0.001); participants 50 years or older showed greater overall improvement than those younger than 50; indicating these variables did influence participants’ scores. An overall score improvement of 14.2% was observed across study participants. The largest improvement (38%) was confidence in knowing which records to save after a cancer diagnosis. Participants felt the video was helpful (89%), the GROUPS checklist was useful (89%), and 92% felt motivated to find and save the recommended documents.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US. The combination of noncurative treatments and severe comorbidities are significant contributors to this high mortality rate. In recent years, the use of adoptive T-cell therapy (ACT), leveraging the body’s own immune system to recognize and target cancer has become increasingly popular. Unfortunately, while ACT has been successful in the treatment of hematological malignancies, it is less efficacious in CRC due to tumor heterogeneity and the lack of targetable antigens. In response to the need for improved treatment options with greater specificity and efficacy, the purpose of this thesis is to systematically review the efficacy and safety of adoptive T-cell therapy in CRC and to optimize ACT methods to increase potency towards CRC tumors in vitro.

Lynch syndrome causes increased risks of developing colorectal, endometrial, ovarian, and other cancers. Current screening guidelines for gynecological cancers are vague and often left to a clinician’s discretion whether to recommend them. Individuals at risk of developing gynecological cancers often view screening as important whereas some providers believe it is more important to stress prophylactic hysterectomy and oophorectomy for their patients with Lynch syndrome. This study aimed to identify factors associated with decisions to undergo prophylactic surgery or pursue regular gynecological screening. A survey to collect information about individuals with Lynch syndrome was distributed to online and social media based support groups. Participants included 115 individuals without a history of gynecological cancer who had an intact uterus and/or ovaries when they received their genetic testing results identifying Lynch syndrome. Participants’ demographics, genetic testing and Lynch syndrome history, gynecological healthcare decisions, and Lynch syndrome education were collected. It was found that age, having less than a college degree, having children, not desiring future pregnancies, and having a previous non-gynecological cancer are significantly associated with choosing to undergo both prophylactic hysterectomy and oophorectomy.

Menopausal status at the time of genetic test results was also associated with the decision to undergo one or both surgeries. Characteristics that are associated with level of risk, including

individual gene mutation or family history of gynecological cancer, were not associated with surgical decisions. Receiving information about symptoms of gynecological cancer was significantly associated with pursuing regular gynecological cancer screening while receiving information about Lynch syndrome related gynecological cancer risks and gynecological cancer screening were approaching a significant association. Participant comments also provided insight into emotional factors experienced while navigating decisions to undergo gynecological cancer screening and/or prophylactic hysterectomy and oophorectomy. These results serve as a reminder that decision-making is not straightforward. Each person will be influenced by their personal experiences and healthcare encounters when making medical management decisions. Approaching encounters with patient centered care and information gained by listening to members of the Lynch syndrome community may help facilitate trusting relationships and ultimately empower patients to be aware of their personal risks and make confident, informed decisions about their gynecological health and wellness.

Lifestyle risk factors are known to increase the risks for certain cancers. However, these factors are often not discussed during hereditary cancer risk counseling. This study explored self-reported improvements to lifestyle risk factors and perception of cancer risk in the setting of hereditary cancer risk counseling. The study involved 2,000 participants undergoing genetic counseling at three California hospitals who completed pre-counseling and post-testing surveys, with questions pertaining to risk perception and changes to modifiable lifestyle risk factors.

Results from this study give insight into lifestyle improvements made in the setting of genetic counseling and testing. Over a third of the study participants indicated that they made a lifestyle improvement. Participants with modifiable lifestyle risk factors were not more likely to make improvements to lifestyle than participants without these lifestyle risk factors; they were also not more likely to perceive they were at higher risk for specific cancers. Participants who tested negative for a mutation did not improve their lifestyle more often than those who tested positive for a mutation.

This study identifies a gap in knowledge of cancer risk in participants with modifiable lifestyle risk factors. It also highlights that mutation carriers are engaging in lifestyle improvements even though the benefit to them is not well understood. Thus, it may be important for genetic counselors to address lifestyle risk factors during risk counseling. Future studies may focus on understanding the impact and efficacy of lifestyle risk counseling during hereditary cancer counseling.

Various commercial laboratories are used in cancer genetics practice, which can lead to clinicians receiving reports with conflicting categorizations of genetic variants. Such discrepancies can have significant clinical implications and can potentially lead to different counseling approaches for different patients with the same variant. In this study, we describe the frequency of this occurrence, analyze genetics providers’ awareness of conflicting interpretations, and make comparisons of medical management recommendations provided to patients with discrepant classifications of the same variant. A cohort of 2,000 patients was recruited from three cancer genetics clinics from 2014 to 2016. All patients underwent the same hereditary cancer panel by one major commercial genetics laboratory. A review of ClinVar archives was performed to identify clinically significant conflicts between ClinVar and the test report, defined as either a variant of uncertain significance (VUS) on the test report with a pathogenic/likely pathogenic (P/LP) classification by major lab in ClinVar, or a P/LP variant on the test report with a VUS classification by a major lab in ClinVar. We demonstrate that 2.5% of patients had a variant with a clinically significant conflict in ClinVar when the test report was issued, including 19 patients with a P/LP variant reported in APC or MUTYH, and 31 patients with a VUS reported in CDKN2A, CHEK2, MLH1, MSH2, MUTYH, RAD51C, or TP53. For patients with a VUS on their report who had a clinically significant conflict, analysis of available study case report forms and original results disclosure clinic notes revealed that only 10/28 (36%) of patients appeared to be counseled by a provider who was aware of the conflict. Patients in this cohort with clinically significant conflicts were then compared to patients outside the cohort who had been tested by the same providers utilizing different laboratories. A detailed case analysis led to the finding that discrepant counseling strategies were utilized for different patients with the same variant, within the same institution and even by the same counselor. The results of this study provide evidence that variant interpretation discrepancies have implications in medical management decisions. This highlights the importance of clinician awareness for possible conflicts in variant interpretation. Initiatives to harmonize variant classifications are critical to resolving discrepant interpretations and supporting clinicians in providing accurate risk assessment.

Purpose Classification changes for bronchioloalveolar carcinoma (BAC) by the WHO in May 1999 narrowed its definition. This study was undertaken in an attempt to characterize the impact of these changes on the epidemiology of BAC. Patients and Methods This retrospective study involves data analysis from the population-based Cancer Surveillance Programs of three Southern California counties from 1995 to 2003. BAC cases diagnosed after May 1999 are compared with BAC cases before that time by clinicopathologic variables including survival. Results Incident cases (11,969) of non-small-cell lung cancer (NSCLC) were analyzed, including 626 cases of BAC (5.2%). Median overall survival (OS) for BAC patients diagnosed after May 1999 (> 53 months) was significantly improved over median OS for BAC patients before May 1999 (32 months; P = .012). This survival benefit remained after adjustment for sex, smoking status, and stage at presentation (hazard ratio for time of diagnosis before May 1999 compared with a diagnosis after May 1999 = 1.43; P = .015). Median CS for non-BAC NSCLC patients diagnosed before May 1999 (9 months) did not differ from the median OS of such patients afterwards (110 months; P = .09). Conclusion This epidemiologic study is the first to demonstrate a survival advantage for BAC patients diagnosed after May 1999 compared with BAC patients diagnosed before this time-a finding that persists after adjustment for sex, smoking status, and stage at presentation. We believe that this observed survival benefit likely reflects changes in the revised 1999 WHO classification.

Background

Materials and methods

Results

Conclusions

Background

Methods

Results

Conclusion

Background

Methods

Results

Conclusions