Non–small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges

BACKGROUND

Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated.

METHODS

The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment.

RESULTS

In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients.

CONCLUSIONS

Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017. © 2017 American Cancer Society.

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Implementation of precision medicine in clinical trials in thoracic oncology: Which are the hurdles?

Precision medicine quite likely will be implemented at a different pace than originally hypothesized, but it is definitely the way to move forward. Even from a medical oncology perspective, a clear understanding of the changes in a molecular pathway and the timely application of a diagnostic assay are critical steps to ultimately deliver a better treatment choice to each individual patient with nonsmall cell lung cancer. See also pages 000-000.

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Prognostic Awareness and Communication Preferences among Caregivers of Patients with Malignant Glioma

Abstract

Objective

Malignant glioma is a devastating neuro-oncologic disease with almost invariably poor prognosis, yet many families facing malignant glioma have poor prognostic awareness (PA), or the awareness of the patient's incurable disease and shortened life-expectancy. Accurate PA is associated with favorable medical outcomes at the end-of-life for patients and psychosocial outcomes for informal caregivers (ICs) through bereavement. To date, however, no study has specifically examined PA among MG ICs and the information they receive that shapes their awareness.

Methods

Thirty-two ICs of patients with malignant glioma completed a semi-structured assessment of their awareness of the incurability and life expectancy of their loved one's illness, and to understand their sources of prognostic information and preferences for communication of prognostic information.

Results

Twenty two (69%) ICs had full PA - awareness of the incurability of malignant glioma and accurate estimates of their loved ones' life expectancy. Twenty-three (72%) felt that prognostic information was extremely or very important to possess, and 16 (50%) desired more prognostic information. The majority of ICs received prognostic information from physicians and the Internet. Qualitative analyses revealed that many ICs had difficulty navigating medical encounters in which they concurrently wanted to elicit prognostic information from physicians and protect patients from such information.

Conclusions

Accurate and timely PA is necessary for ICs to serve as critical members of healthcare teams. Interventions are needed to foster ICs' skills in navigating prognostic communication with patients and healthcare providers and thereby improve their ability to advocate for their loved one's wishes.

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A Dyadic Analysis of Stress Processes in Latinas with Breast Cancer and Their Family Caregivers

Abstract

Objective

Breast cancer diagnosis and treatment negatively affect quality of life for survivors and their family caregivers. The stress process model has been useful for describing the cascade of social and psychological experiences that culminate in degraded quality of life for both survivors and their family caregivers. This study is designed to test theoretically specified predictors of negative psychosocial outcomes in a dyadic context.

Method

Participants were 230 dyads comprised of Latinas recently diagnosed with breast cancer and their primary family caregiver, who completed measures of socioeconomic status, stress, family conflict, depression, and anxiety. Data were analyzed following the actor-partner interdependence mediation model (APIMeM) in structural equation modeling.

Results

For both survivors and caregivers there were significant direct and indirect actor effects (through family conflict) of perceived stress on depression and anxiety. Several indirect partner effects were also evident in this sample. Specifically, caregivers' stress was predictive of survivors' depression and anxiety through survivors' increased perceptions of family conflict.

Conclusions

As predicted by the stress process model, stress and family conflict were predictive of psychological distress in breast cancer survivors and their family caregivers. Significant partner effects in the APIMeM suggest that there are some dyadic influences, particularly from caregivers' stress to survivors' perceptions of exacerbated family conflict. These findings show how strained family relationships can aggravate the well-being of cancer survivors and their family caregivers through this challenging experience.

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Non–small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges

BACKGROUND

Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated.

METHODS

The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment.

RESULTS

In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients.

CONCLUSIONS

Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2mbTtGN

Implementation of precision medicine in clinical trials in thoracic oncology: Which are the hurdles?

Precision medicine quite likely will be implemented at a different pace than originally hypothesized, but it is definitely the way to move forward. Even from a medical oncology perspective, a clear understanding of the changes in a molecular pathway and the timely application of a diagnostic assay are critical steps to ultimately deliver a better treatment choice to each individual patient with nonsmall cell lung cancer. See also pages 000-000.

http://ift.tt/2yPQ5Hv

Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation

Abstract

Background

Lung cancer is the leading cause of cancer death worldwide. However, the molecular mechanisms underlying lung cancer development have not been fully understood. The functions of histone deacetylases (HDACs), a class of total eighteen proteins (HDAC1–11 and SIRT1–7 in mammals) that deacetylate histones and non-histone proteins, in cancers are largely unknown.

Methods

Hdac7 ^+/−/K-Ras mice and HDAC7-depleted human lung cancer cell lines were used as models for studying the function of Hdac7 gene in lung cancer. Kaplan-Meier survival analysis was performed to explore the relationship between HDAC7 expression and prognosis of human lung cancers. Recombinant lentivirus-mediated in vivo gene expression or knockdown, Western blotting, and pull-down assay were applied to investigate the underlying molecular mechanism by which Hdac7 promotes lung tumorigenesis.

Results

The number and burden of lung tumor were dramatically reduced in Hdac7 ^+/−/K-Ras mice compared to control K-Ras mice. Also, in Hdac7 ^+/−/K-Ras mice, cell proliferation was significantly inhibited and apoptosis in lung tumors was greatly enhanced. Similarly, cell proliferation and anchorage-independent growth of human lung cancer cell lines expressing shHDAC7 were also significantly suppressed and apoptosis was dramatically elevated respectively. Mechanistic study revealed that Hdac7 mutation in mouse lung tumors or HDAC7 depletion in human tumor cell lines resulted in significantly enhanced acetylation and tyrosine-phosphorylation of Stat3 and HDAC7 protein directly interacted with and deacetylateed STAT3. The Hdac7 mutant-mediated inhibitory effects on lung tumorigenesis in mice and cell proliferation/soft agar colony formation of human lung cancer cell lines were respectively reversed by expressing dnStat3. Finally, the high HDAC7 mRNA level was found to be correlated with poor prognosis of human lung cancer patients.

Conclusion

Our study suggests that Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation via deacetylating Stat3 and may shed a light on the design of new therapeutic strategies for human lung cancer.

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