Impact of Simultaneous Circulating Tumor DNA and Tissue Genotyping in the Workup of Stage IV Lung Adenocarcinoma on Quality of Care in an Academic Community Medical Center.

PURPOSE: In patients with metastatic lung adenocarcinoma, evidence-based first-line treatment decisions require analysis of tumors for genomic alterations (GAs). Optimizing the genotyping paradigm may improve the delivery of precision oncology care. Actionable GAs can be identified by analyzing tumor tissue or circulating tumor DNA using liquid biopsy. Consensus guidelines for when to use liquid biopsy have not been established. We evaluated the routine use of liquid biopsy performed simultaneously with tissue testing in patients with newly diagnosed, stage IV lung adenocarcinoma. METHODS: We performed a retrospective study comparing patients who underwent tissue genotyping alone (standard biopsy group) with patients who had simultaneous liquid and tissue genotyping (combined biopsy group). We examined the time to reach a final diagnosis, the need for repeat biopsies, and diagnostic accuracy. RESULTS: Forty two patients in the combined biopsy group and 78 in the standard biopsy group met the inclusion criteria. The standard group had a mean time to diagnosis of 33.5 days, compared with 20.6 days in the combined group (P < .001 by two-tailed t-test). In the combined group, 14 patients did not have sufficient tissue for molecular analysis (30%); however, in 11 (79%) of these patients, liquid biopsy identified a GA that eliminated the need for a second tissue biopsy. In patients who completed both tests, each test found actionable GAs missed by the other. CONCLUSION: Performing liquid biopsy simultaneously with tissue genotyping is feasible in an academic community medical center. Potential advantages of simultaneous liquid and tissue biopsies include shorter time to obtain a definitive molecular diagnosis, reduced need for a repeat biopsy, and improved detection of actionable mutations, although a sequential strategy that saves costs by beginning with a liquid biopsy may be ideal.

Influence of TP53 Mutation on Survival in Patients With Advanced EGFR-Mutant Non-Small-Cell Lung Cancer.

PURPOSE: TP53 mutation (MT) in epidermal growth factor receptor (EGFR) -MT non-small cell lung cancer (NSCLC) is associated with poor response to targeted therapy; however, its impact on survival is not clearly established. PATIENTS AND METHODS: We performed an analysis of patients with stage IV EGFR MT NSCLC with available gene sequencing data. Associations between baseline characteristics; molecular profile, including TP53 MT; and survival outcomes were assessed. RESULTS: We identified 131 consecutive patients with EGFR MT; 81 (62%) had a TP53 MT, and 55 (42%) had other coexisting oncogenic MTs. Emergent EGFR T790M MT was observed in 42 patients (32%). Overall survival (OS) was longer for younger patients (P = .003), never smokers (P = .002), those with Eastern Cooperative Oncology Group performance status 0 to 1 (P = .004), and emergent T790M MT (P = .018). TP53 MT (P = .021) and other coexisting oncogenic MTs (P = 0.011) were associated with inferior OS. In a multivariable regression analysis adjusted for age, smoking, Eastern Cooperative Oncology Group performance status, and the presence of TP53 MT (P = .063) and other coexisting MTs (P = .064) did not achieve statistical significance. Patients with EGFR T790M/TP53 double MT had worse OS compared with patients with T790M MT alone (46.4 months v 82.9 months). In our series, five patients transformed to small-cell lung cancer (5.6%). All had TP53 MT. In four patients, allelic fraction of TP53 MT increased at the time of transformation. CONCLUSION: The presence of TP53 and other coexisting MTs in EGFR MT NSCLC were associated with inferior OS, including patients with emergent T790M MT. An increase in TP53 mutation allelic fraction may potentially be a useful clinical predictor of small-cell transformation.

Analysis of the Relationship Between Response to Chemotherapy and Response to Radiation Therapy in Patients With Non-Small Cell Lung Cancer Receiving Sequential Treatment.

OBJECTIVES: We examine whether induction chemotherapy response predicts thoracic radiotherapy response in locally advanced or oligometastatic non-small cell lung cancer. MATERIALS AND METHODS: Between January 2001 to August 2010, 25 consecutive patients were identified who received systemic dose chemotherapy followed by definitive thoracic radiotherapy alone. All patients had measurable disease after chemotherapy that was evaluable for response to radiotherapy. Response to each modality was scored by RECIST as stable disease (SD), progressive disease (PD), partial response (PR), or complete response (CR). RESULTS: Patients had adenocarcinoma (n=13), squamous cell carcinoma (n=8), or other histologies (n=4). They had stage IIIA (n=6), IIIB (n=14), and IV (n=5) disease. Patients received 2 to 6 cycles (median 4) of platinum-based chemotherapy followed by radiotherapy (median 66.6/1.8 Gy [range 50 to 84 Gy]). Median time between chemotherapy end and radiotherapy start was 6.7 weeks (range, 1.6 to 53.4 wk). Twelve patients responded to chemotherapy (all were PRs) and 13 did not (SD+PD). Fifteen patients responded to radiotherapy (7 CR, 8 PR) and 10 did not (SD+PD). Of the 12 patients who responded to chemotherapy, 8 also responded to radiotherapy (4 CR, 4 PR). Of the 13 chemotherapy nonresponders, 7 responded to radiotherapy (3 CR, 4 PR). χ analysis did not find any association between chemotherapy and radiotherapy response (P=0.513). Regression analysis also failed to identify any correlation between chemotherapy and radiotherapy response (r=0.008). CONCLUSIONS: This study suggests that response to chemotherapy does not predict response to radiotherapy in locally advanced or oligometastatic non-small cell lung cancer. Lack of response to chemotherapy, therefore, should not preclude treatment with definitive radiotherapy.

Using Maslow's hierarchy to highlight power imbalances between visiting health professional student volunteers and the host community: An applied qualitative study.

BACKGROUND: Health professional students from high-income countries increasingly participate in short-term experiences in global health (STEGH) conducted abroad. One common criticism of STEGH is the inherent power differential that exists between visiting learners and the local community. To highlight this power differential, this paper explores perceived benefits as described by volunteer and community respondents and applies Maslow's hierarchy of needs to commonly identified themes in each respondent group. METHODS: A semistructured survey was used to collect qualitative responses from both volunteers and community members located in a Dominican Republic community, that is, a hotspot for traditionally conducted STEGH. Thematic analysis identified themes of perceived benefits from both respondent groups; each group's common themes were then classified and compared within Maslow's hierarchy of needs. RESULTS: Each respondent group identified resource provision as a perceived benefit of STEGH, but volunteer respondents primarily focused on the provision of highly-skilled, complex resources while community respondents focused on basic necessities (food, water, etc.) Volunteer respondents were also the only group to also mention spiritual/religious/life experiences, personal skills development, and relationships as perceived benefits. Applying Maslow's hierarchy thus demonstrates a difference in needs: community respondents focused on benefits that address deficiency needs at the bottom of the hierarchy while volunteers focused on benefits addressing self-transcendence/actualization needs at the top of the hierarchy. CONCLUSIONS: The perceived difference in needs met by STEGH between volunteers and the host community within Maslow's hierarchy may drive an inherent power differential. Refocusing STEGH on the relationship level of the hierarchy (i.e., focusing on partnerships) might help mitigate this imbalance and empower host communities.

Complementary and alternative medicine use and benefit finding among cancer patients.

PURPOSE: An increasing number of cancer patients are choosing Complementary and Alternative Medicine (CAM) as an active way to manage the physical, psychological, and spiritual consequences of cancer. This trend parallels a movement to understand how a difficult experience, such as a cancer diagnosis, may help facilitate positive growth, also referred to as benefit finding. Little is known about the associations between the use of CAM and the ability to find benefit in the cancer experience. METHODS: We conducted a cross-sectional survey of medical oncology outpatients in an urban academic cancer center. Patients completed measures of CAM use and benefit finding following a diagnosis of cancer. A hierarchical regression, adjusting for covariates, was performed to evaluate the unique contribution of CAM use on benefit finding. The relationship between specific CAM modalities and benefit finding was explored. RESULTS: Among 316 participants, 193 (61.3%) reported CAM use following diagnosis. Factors associated with CAM use were female gender (p=0.005); college, or higher, education (p=0.09); breast cancer diagnosis (p=0.016); and being 12 to 36 months post-diagnosis (p=0.017). In the hierarchical regression, race contributed the greatest unique variance to benefit finding (23%), followed by time from diagnosis (18%), and age (14%). Adjusting for covariates, CAM use uniquely accounted for 13% of the variance in benefit finding. Individuals using energy healing and healing arts reported significantly more benefit than nonusers. Special diet, herbal remedies, vitamin use, and massage saw a smaller increase in benefit finding, while acupuncture, chiropractic, homeopathy, relaxation, yoga, and tai chi were not significantly associated with benefit finding. CONCLUSIONS: Patients who used CAM following a cancer diagnosis reported higher levels of benefit finding than those who did not. More research is required to evaluate the causal relationship between CAM use, benefit finding, and better psychosocial well-being.