Abstract
Purpose
Tumor biopsies are critical for delineating pharmacodynamic effects of drugs and for optimal patient selection during oncology clinical trials of molecular targeted therapies. The purpose of this study was to identify factors related to patients’ willingness to provide study-related tumor biopsies in phase 1 clinical trials of molecularly targeted therapy.
Methods
An investigator-designed survey, that assessed biopsy willingness, demographic and clinical factors, was completed anonymously by patients with advanced cancer in a phase 1 clinic for targeted therapy. Data were analyzed using multivariate logistic regression models with odds ratios (OR) and 95 % confidence intervals (CI).
Results
Three hundred and sixty-two patients with advanced cancer (50 % male, 56 % aged ≤60 years) participated. In univariate analyses, willingness to provide study-related biopsy was associated with male gender, white race, higher income, using the Internet for cancer-related information, and having had a biopsy previously (p < 0.05). In multivariate analyses, male gender (OR 2.41, 95 % CI 1.54, 3.78) and having had a biopsy (OR 3.71, 95 % CI 1.68, 8.15) were associated with willingness to have one biopsy; male gender (OR 1.97, 95 % CI 1.30, 3.00) and relying on the Internet as a source of information (OR 1.87, 95 % CI 1.21, 2.89) were associated with willingness to have more than one biopsy.
Conclusions
The results suggest that male gender is associated with greater stated willingness to undergo biopsy. Also, the Internet is an important source of information for patients with cancer and may strongly influence their decisions about whether to consent to biopsies in early clinical trials.
Keywords: Biopsy, Cancer, Clinical trial, Internet, Oncology, Patient
Introduction
Tumor sampling via biopsy plays an important role in clinical cancer research as well as clinical practice. Repeated biopsies may be essential for defining a tumor’s molecular characteristics (Kluger et al. 2011; Yu et al. 2009), signals mediating resistance, underlying reasons for a mixed response (including the biology behind the heterogeneity of metastases) (Mego et al. 2011; Izzedine et al. 2006), and the pharmacodynamic impact of novel targeted drugs in a phase 1 setting.
Early clinical trials of molecular targeted agents generally focus on assessments of safety, maximum tolerated dose, pharmacokinetics (Eisenhauer et al. 2006), and response signals (Flaherty et al. 2010). However, recognition is growing regarding the importance of pharmacodynamics in the early clinical trial process. Pharmacodynamic studies, which define the impact of a drug on its target (Eisenhauer et al. 2006), can be instrumental in identifying the optimal biologic dose for phase 2 studies.
Single and sequential/repeated tumor biopsies serve three important functions in early clinical trials. First, single biopsies are useful in identifying patients who would be most likely to respond to therapy. Better patient selection has demonstrated higher response rates in clinical trials of molecular targeted therapies (Kluger et al. 2011) and may facilitate accelerated drug approval (Kwak et al. 2010; Chabner 2010). Second, sequential tumor biopsies are often used to delineate the pharmacodynamic effects of drugs and evaluate biologic or pharmacodynamic endpoints (Flaherty et al. 2010; Stewart and Kurzrock 2009). Third, single or sequential tumor biopsies in patients with progressive disease can help us to better understand mechanisms of drug resistance (Sequist et al. 2011).
In practice, however, obstacles are commonly encountered in obtaining tumor tissue during the clinical trial from participants (Dowlati et al. 2001). There is limited research on which specific factors/characteristics influence a patient’s willingness to undergo a biopsy procedure during early clinical trials. The purpose of the present study was to identify factors related to patients’ decisions to agree to provide study-related biopsies.
Methods
Participants
Patients with advanced malignancies who presented to the phase 1 clinic in the Clinical Center for Targeted Therapy at The University of Texas MD Anderson Cancer Center (MD Anderson) were recruited to participate in the study. Inclusion criteria were a clinical or histological diagnosis of advanced malignancy, age ≥18 years, and ability to read and understand English, Spanish, or Arabic. Exclusion criteria included any clinically relevant conditions, such as problems with vision, cognitive impairment, or acute mental illness that, in the opinion of the physician principal investigator, could interfere with completing the study. The study was approved by the Psychosocial, Behavioral, and Health Services Research Committee and the Institutional Review Board at MD Anderson, and participants gave informed consent.
Study design
The present study was designed to determine factors related to decisions to participate in study-related biopsies among patients in the phase 1 clinic at MD Anderson. A study coordinator approached patients who presented for their scheduled clinical appointments. Patients dropped anonymously completed questionnaires into a locked box in the clinic reception area, which was removed from the patient rooms and the workrooms for physicians and clinical personnel. Given that surveys were completed anonymously, patient identifying information was not revealed to any entities, including the research team at MD Anderson.
The same study coordinator approached all participants using a standard script and ensured that potential participants fully understood the objectives and requirements of the study. Furthermore, the study coordinator assured participants that their involvement in the study would remain confidential, and that their survey responses would remain anonymous. All recruitment activities conformed to policies of the 1996 Health Information Portability and Accountability Act.
Data collection instrument
The survey instrument included questions to determine patient willingness to undergo one or more biopsies, demographic characteristics (for example, age, gender, race/ethnicity, education, prior cancer treatments, quality of life [QOL] scores), patients’ sources of information for learning about their disease, and biopsy experience-related factors (for example, having had a biopsy previously). The questions were developed based on the phase 1 clinical trial and research survey development experience of the investigative team. The survey instrument was provided to faculty physicians on phase 1 clinical trials for suggestions and comments, which were incorporated. The survey instrument was translated into English, Spanish, and Arabic languages frequently spoken by patients at MD Anderson.
Statistical analysis
Summary statistics were used to describe demographic and other survey responses. The primary outcome was the proportion of patients willing to undergo a biopsy procedure. Patients were categorized based on willingness to provide biopsy samples. Chi-square tests evaluated associations between patients’ demographic/sources of information to learn about their disease/biopsy experience-related factors and willingness to provide biopsy.
Logistic regression models assessed the impact of demographics, patients’ sources of information to learn about cancer, and biopsy experience-related factors on the likelihood of patients’ willingness to undergo biopsy. An ordinal logistic regression model was used as responses to the main outcome variables of interest were ordered/ranked (with response options “yes,” “no,” or “maybe”). Factors were considered for inclusion in the multivariate models if their univariate p values were <0.05. A backward elimination model selected factors that had statistical significance for the final multivariate model. Results of logistic regression analyses are presented as odds ratios (OR) and 95 % confidence intervals (CI).
Statistical analyses were conducted using SAS (version 9.1.3, SAS Institute Inc., Cary, NC). All tests were two-sided, and statistical significance was set at p value <0.05. Further descriptive data were obtained for reasons why some patients chose the “yes,” “no,” or “maybe” responses to the questions relating to willingness to obtain an optional biopsy or >1 biopsy. All statistical analyses were verified by a statistician (XL).
Results
Patient accrual for the study began in November 2009. Surveys were given to 502 participants, and 362 patients returned questionnaires, a 72.1 % response rate. Percentages reported for results are based on number of patients responding to each question.
Demographic characteristics and prior cancer treatments of patients are shown in Table 1. Most patients were ≤60 years of age (55.5 %), white (81 %), from the United States (96 %) and had college or professional degrees (74.0 %). Fifty-four percent of patients reported annual incomes ≤$60,000, and 38 % rated their quality of life as very good or excellent. The most frequently reported prior cancer treatment by patients was chemotherapy (91.9 %), then surgery (62.5 %), radiation (52.1 %), and biologic or molecularly targeted therapy (49.3 %). The most common tumor sites were colorectal (16.7 %), lung (15.8 %), melanoma (11.9 %), and head and neck (11.1 %).
Table 1.
Demographic characteristics and prior cancer treatments of patients with advanced cancer in a phase 1 clinic for molecularly targeted therapy
| Characteristic | Number of patients | %a |
|---|---|---|
| Age, years (n = 362) | ||
| ≤60 | 201 | 55.5 |
| >60 | 161 | 44.5 |
| Sex (n = 356) | ||
| Female | 179 | 50.3 |
| Male | 177 | 49.7 |
| Race/ethnicity (n = 347) | ||
| African–American | 32 | 9.2 |
| Asian/Pacific Islander | 11 | 3.2 |
| White | 280 | 80.7 |
| Hispanic | 22 | 6.3 |
| Other | 2 | 0.6 |
| Education (n = 354) | ||
| High school or lower | 92 | 26.0 |
| College | 195 | 55.1 |
| Professional degree | 67 | 18.9 |
| Employment (n = 352) | ||
| Employed | 157 | 44.6 |
| Retired | 141 | 40.1 |
| Unemployed | 54 | 15.3 |
| Income, annual (n = 311) | ||
| ≤60,000 | 169 | 54.3 |
| >60,000 | 142 | 45.7 |
| Quality of life (n = 357) | ||
| Poor/Fair | 91 | 25.5 |
| Good | 132 | 37.0 |
| Very good | 104 | 29.1 |
| Excellent | 30 | 8.4 |
| Prior cancer treatmentsb (n = 357) | ||
| Biologic or targeted therapy | 176 | 49.3 |
| Chemotherapy | 328 | 91.9 |
| Radiation | 186 | 52.1 |
| Surgery | 223 | 62.5 |
aPercentages are based on the number of patients who answered each question (n)
bAs some patients reported multiple prior cancer treatments, the total percentage for this question may exceed 100
Table 2 presents patients’ sources of cancer-related information and biopsy experience-related characteristics. Sources of information used by patients to learn about their disease included physicians (94.2 %), the Internet (65.3 %), and other patients (24.7 %). Internet sites reported by patients as being used most frequently to obtain information about cancer were medical information sites such as WebMD, Wrong Diagnosis, Health Central, or Health A to Z (55 %), and the National Cancer Institute Web site (51 %). Of the 349 patients who responded to the question about having a previous biopsy, 87.1 % reported having had a previous biopsy, with 74.3 % reporting above average to very favorable ratings of their previous biopsy experience. Of those who responded to the question, 84.1 % of responders reported no biopsy-related complications.
Table 2.
Sources of information to learn about cancer, and previous biopsy experience-related characteristics of patients with advanced cancer in a phase 1 clinic for molecularly targeted therapy
| Characteristic | Number of patients | %a |
|---|---|---|
| Patients’ sources of information to learn about cancerb (n = 360) | ||
| Physician | 339 | 94.2 |
| Internet | 235 | 65.3 |
| Other patients | 89 | 24.7 |
| Other | 50 | 13.9 |
| Patients’ reported understanding of their disease (n = 354) | ||
| 0–2 (“0” indicates “not at all”) | 53 | 15.0 |
| 3–5 (“5” indicates “very well”) | 301 | 85.0 |
| Have you ever had a biopsy before coming to this clinic? (n = 349) | ||
| No | 45 | 12.9 |
| Yes | 304 | 87.1 |
| How anxious did you feel prior to the biopsy? (n = 308) | ||
| 0–2 (“0” indicates “very anxious”) | 38 | 43.8 |
| 3–5 (“5” indicates “not at all anxious”) | 173 | 56.2 |
| Rating of prior biopsy experience (n = 300) | ||
| 0–2 (“0” indicates “very bad”) | 16 | 25.7 |
| 3–5 (“5” indicates “very good”) | 223 | 74.3 |
| Adequately informed about the procedure? (n = 308) | ||
| No | 24 | 7.8 |
| Somewhat | 49 | 15.9 |
| Yes | 235 | 76.3 |
| Had any complications related to the biopsy? (n = 309) | ||
| No | 260 | 84.1 |
| Yes | 49 | 15.9 |
| Have undergone a biopsy in present clinical trial? (n = 319) | ||
| No | 281 | 88.1 |
| Yes | 38 | 11.9 |
a Percentages are based on the number of patients who answered each question (n)
b As some patients reported multiple sources of information to learn about cancer, the total percentage for this question may exceed 100
Proportions of patients reporting “yes,” “no,” and “maybe” to the question regarding willingness to provide an optional biopsy were 45.9, 16.5, and 37.6 %, respectively. In univariate analyses, those willing to provide an optional biopsy on a clinical trial were more likely to be men (p = 0.002), less likely to report feeling anxious prior to a previous biopsy (p = 0.020), and more likely to have had a biopsy in the current trial (p = 0.001).
Proportions of patients responding “yes,” “no,” and “maybe” to the question on willingness to enroll in a clinical trial with more than one biopsy were 42.6, 13.6, and 43.8 %, respectively. In univariate analyses, patients’ willingness to enroll in a clinical trial with more than one biopsy was associated with male versus female gender (p = 0.004), white versus non-white race/ethnicity (p = 0.021), higher versus lower income (p = 0.015), higher versus lower reported QOL (p = 0.009), reporting versus not reporting physicians (p = 0.001) or the Internet (p = 0.016) as sources of cancer-related information, lower versus higher reported anxiety prior to previous biopsies (p = 0.004), and superior versus lower ratings of previous biopsy experience (p = 0.040) (Table 3).
Table 3.
Univariate analyses of associations between patients’ willingness to enroll in clinical trials with more than one biopsy and selected demographic, sources of information related, and biopsy experience-related characteristics in patients with advanced cancer in a phase 1 clinic for molecularly targeted therapy
| Characteristic | No (n = 46) | Maybe (n = 148) | Yes (n = 144) | ||||
|---|---|---|---|---|---|---|---|
| n | % | n | % | n | % | p a | |
| Age, years | |||||||
| ≤60 | 25 | 13.1 | 79 | 41.4 | 87 | 45.5 | NS |
| >60 | 21 | 14.3 | 69 | 46.9 | 57 | 38.8 | |
| Gender | |||||||
| Female | 29 | 17.6 | 80 | 48.5 | 56 | 33.9 | 0.004 |
| Male | 16 | 9.5 | 67 | 39.9 | 85 | 50.6 | |
| Race | |||||||
| Non-White | 13 | 22.8 | 28 | 49.1 | 16 | 28.1 | 0.021 |
| White | 32 | 12.0 | 114 | 42.7 | 121 | 45.3 | |
| Income/years | |||||||
| ≤60,000 | 19 | 12.0 | 79 | 50.0 | 60 | 38.0 | 0.015 |
| >60,000 | 16 | 11.7 | 47 | 34.3 | 74 | 54.0 | |
| Quality of life | |||||||
| Poor–Good | 38 | 18.4 | 85 | 41.1 | 84 | 40.6 | 0.009 |
| Very good–excellent | 8 | 6.3 | 61 | 48.4 | 57 | 45.2 | |
| Understand cancer well | |||||||
| No | 20 | 14.4 | 70 | 50.4 | 49 | 35.3 | NS |
| Yes | 25 | 13.0 | 76 | 39.4 | 92 | 47.7 | |
| Chemotherapy | |||||||
| No | 6 | 17.6 | 8 | 23.5 | 20 | 58.8 | 0.043 |
| Yes | 40 | 13.2 | 140 | 46.1 | 124 | 40.8 | |
| Biologic or targeted therapy | |||||||
| No | 24 | 14.3 | 66 | 39.3 | 78 | 46.4 | NS |
| Yes | 22 | 12.9 | 82 | 48.2 | 66 | 38.8 | |
| Physician as a source of information to learn about disease | |||||||
| No | 8 | 42.1 | 4 | 21.1 | 7 | 36.8 | 0.001 |
| Yes | 38 | 12.0 | 142 | 44.8 | 137 | 43.2 | |
| Internet as a source of information to learn about disease | |||||||
| No | 22 | 18.6 | 57 | 48.3 | 39 | 33.1 | 0.016 |
| Yes | 24 | 11.0 | 89 | 40.8 | 105 | 48.2 | |
| Had a biopsy before? | |||||||
| No | 6 | 14.3 | 21 | 50.0 | 15 | 35.7 | NS |
| Yes | 38 | 13.2 | 121 | 42.2 | 128 | 44.6 | |
| How anxious did you feel prior to the biopsy? | |||||||
| 0 (Very anxious) | 9 | 25.0 | 17 | 47.2 | 10 | 27.8 | 0.004 |
| 1 | 4 | 8.5 | 25 | 53.2 | 18 | 38.3 | |
| 2 | 4 | 8.7 | 18 | 39.1 | 24 | 52.2 | |
| 3 | 11 | 17.7 | 23 | 37.1 | 28 | 45.2 | |
| 4 | 0 | 0.0 | 27 | 50.9 | 26 | 49.1 | |
| 5 (Not anxious at all) | 10 | 20.8 | 13 | 27.1 | 25 | 52.1 | |
| Rating of prior biopsy experience | |||||||
| 0 (Very bad) | 3 | 18.8 | 10 | 62.5 | 3 | 18.8 | 0.04 |
| 1 | 3 | 15.8 | 12 | 63.2 | 4 | 21.1 | |
| 2 | 5 | 12.5 | 17 | 42.5 | 18 | 45.0 | |
| 3 | 14 | 18.4 | 30 | 39.5 | 32 | 42.1 | |
| 4 | 6 | 8.5 | 31 | 43.7 | 34 | 47.9 | |
| 5 (Very good) | 6 | 10.0 | 18 | 30.0 | 36 | 60.0 | |
| Have any complications related to the biopsy? | |||||||
| No | 32 | 13.1 | 98 | 40.0 | 115 | 46.9 | NS |
| Yes | 7 | 15.2 | 23 | 50.0 | 16 | 34.8 | |
| Had a biopsy in current trial | |||||||
| No | 43 | 15.9 | 123 | 45.4 | 105 | 38.7 | NS |
| Yes | 3 | 8.1 | 13 | 35.1 | 21 | 56.8 | |
a p values are based on chi-squared analyses
NS not significant
Table 4 summarizes factors identified through multivariate logistic regression analyses to be associated with willingness to undergo optional biopsy, which were male versus female gender (OR 2.41, 95 % CI 1.54, 3.78), and having had a biopsy in the current trial (OR 3.71, 95 % CI 1.68, 8.15). Factors linked with willingness to enroll in clinical trials requiring more than one biopsy were male versus female gender (OR 1.97, 95 % CI 1.30, 3.00) and use of the Internet as a source of cancer-related information (OR 1.87, 95 % CI 1.21, 2.89).
Table 4.
Multivariate ordinal logistic regression analyses for willingness to undergo biopsy in patients with advanced cancer in a phase 1 clinic for molecularly targeted therapy
| Characteristic | OR | 95 % CI | p |
|---|---|---|---|
| Would you consider an optional biopsy on a clinical trial? | |||
| Gender: male versus female | 2.41 | 1.54, 3.78 | <0.001 |
| Having undergone a biopsy in the current clinical trial: yes versus no | 3.71 | 1.68, 8.15 | 0.001 |
| Would you consider enrolling in a clinical trial that required more than one biopsy? | |||
| Gender: male versus female | 1.97 | 1.30, 3.00 | 0.001 |
| Internet as a source of information: yes versus no | 1.87 | 1.21, 2.89 | 0.005 |
OR odds ratio, CI confidence intervals
A summary of the descriptive data provided by patients on specific reasons for their “no,” “maybe,” and “yes” responses to questions regarding willingness to provide biopsy samples follows (Table 5). Patients’ primary reasons for answering “yes” to questions regarding willingness to provide an optional or more than one biopsy were “to learn about my disease and help other patients” (29.1 % for an optional biopsy and 27 % for >1 biopsy), the belief that information from biopsy results would be useful for future treatment options (28.3 % for an optional biopsy and 25.1 % for >1 biopsy), or useful for their current trial (24.9 % for an optional biopsy and 22.8 % for >1 biopsy). Among those who answered “maybe” regarding willingness to provide an optional and more than one biopsy, scenarios that would make them change their minds were “only if the information will be useful for my future treatment options” (32.4 % for an optional biopsy and 27.9 % for >1 biopsy), and “only if it would help us to learn more about my disease and help other patients” (18.1 % for an optional and 22.5 % for >1 biopsy), and “only if the biopsy information may be useful to inform my current clinical trial” (18.1 % for an optional, 8.5 % for >1 biopsy). The primary reason for answering “no” to the question about willingness for an optional biopsy was that it would not contribute to the management of the patients’ cancer (34.9 %). The main reasons for answering “no” to the question on more than one biopsy were that it would not contribute to the management of the patients’ cancer (25 %), fear of complications (21.7 %), or a negative experience with a previous biopsy (13.3 %), or that a biopsy was not convenient (13.3 %).
Table 5.
Reasons for “no,” “maybe,” and “yes” responses to questions regarding willingness to provide biopsies ranked in order to highest frequencies in patients with advanced cancer in a phase 1 clinic for molecularly targeted therapy
| Reason | Willingness for an optional biopsy | Willingness to enroll in a clinical trial with more than one biopsy | ||||
|---|---|---|---|---|---|---|
| Frequency | % excluding missing | Rank | Frequency | % excluding missing | Rank | |
| Reasons for a response of “yes” | ||||||
| Yes, I hope we can learn about my disease and help other patients | 111 | 29.1 | 1 | 116 | 27.0 | 1 |
| Yes, the biopsy information may be useful for my future treatment options | 108 | 28.3 | 2 | 108 | 25.1 | 2 |
| Yes, the biopsy information may be useful to inform my current clinical trial | 95 | 24.9 | 3 | 98 | 22.8 | 3 |
| Yes, I hope we can learn more about all cancers | 61 | 16.0 | – | 67 | 15.6 | – |
| Other | 4 | 1.1 | – | 2 | 0.5 | |
| I don’t know | 3 | 0.8 | – | 2 | 0.5 | – |
| Yes, if this trial was my only option for a clinical trial | – | – | – | 37 | 8.6 | – |
| Reasons for a response of “maybe” | ||||||
| Yes, only if the biopsy information will be useful for my future treatment options | 68 | 32.4 | 1 | 72 | 27.9 | 1 |
| Yes, only if I knew it would help us learn more about my disease and help other patients | 38 | 18.1 | 2 | 58 | 22.5 | 2 |
| Yes, only if the biopsy information may be useful to inform my current clinical trial | 38 | 18.1 | 2 | 40 | 8.5 | – |
| Yes, only if I knew I would not have any complications | 22 | 10.5 | – | 27 | 10.5 | 3 |
| Yes, only if this trial was my only option for a clinical trial | 20 | 9.5 | – | 27 | 10.5 | 3 |
| I don’t know | 15 | 7.1 | – | 15 | 5.8 | – |
| Other | 9 | 4.3 | – | 19 | 7.4 | – |
| Reasons for a response of “no” | ||||||
| No, it would not contribute to the management of my cancer | 22 | 34.9 | 1 | 15 | 25.0 | 1 |
| Other reason | 11 | 17.5 | 2 | 10 | 16.7 | 3 |
| No, it is too inconvenient | 10 | 15.9 | 3 | 8 | 13.3 | – |
| No, I am afraid of the complications | 9 | 14.3 | – | 13 | 21.7 | 2 |
| No, I am afraid my insurance will not cover it. | 6 | 9.5 | – | 6 | 10.0 | – |
| No, I had a bad experience with my last biopsy | 5 | 7.9 | – | 8 | 13.3 | |
Discussion
Our results suggest that demographic characteristics (such as male gender, white race/ethnicity), superior QOL scores, patients’ sources of information to learn about their disease (such as patients’ relying on the Internet or physicians as sources of information), and biopsy experience-related factors (such as lower anxiety prior to previous biopsy and superior rating of previous biopsy experience) strongly influence a patient’s willingness to undergo biopsy. In multivariate analyses, male gender was selected as an independent predictor for willingness to undergo one or more than one biopsy procedure. Using the Internet as a source of information was also an independent predictor for willingness to undergo more than one biopsy procedure.
Male gender was associated with a greater reported willingness to undergo one or more biopsies. A previous study among end-stage cancer patients (Maida et al. 2010) found that men were more likely than women to be willing to use feeding tubes (p < 0.04) and other forms of aggressive medical management, including chemotherapy, or anticoagulants. Also, a study in terminal cancer patients (Jimenez-Gordo et al. 2009) found that men were less likely than women to report prevalence of all symptoms including visceral pain, constipation, nausea, and vomiting, with the exception of dyspnea. However, in a previous retrospective review performed in our clinic, patients who most frequently actually underwent elective biopsy were women (57.5 %), with most (60.9 %) having gynecologic or breast cancer (El-Osta et al. 2011). These results suggest the possibility of inconsistency between patients’ stated and actual willingness to undergo biopsy, or that other unrelated factors (e.g., tumor accessibility and overall health of patient) influence who actually does consent to biopsy.
In univariate analyses, white patients were more willing than non-white patients to provide more than one biopsy. A caveat here is that race/ethnicity was not an independent predictor of biopsy willingness in multivariate analyses. However, training of health care personnel to build greater trust among patients of all races/ethnicities from the initial point of contact in cancer care is optimal.
Together with biologic and pharmacokinetic measures, QOL has been used previously to measure patient satisfaction (Crook et al. 2011), patient prognosis (Bernhard et al. 2010), and response to or efficacy of treatment in cancer clinical trials (Crook et al. 2011; Sherrill et al. 2010). The high proportion (>70 %) of phase 1 clinical trial patients in the present study rating their QOL as “good” to “excellent” is encouraging. Also, interesting was that a high proportion (87.1 %) of patients in the present study had had a previous biopsy, of whom 84.1 % reported no biopsy-related complications.
Willingness to enroll in clinical trials requiring more than one biopsy was linked with greater likelihood of patients’ using physicians or the Internet as sources of information about their disease. Physician input into patient’s understanding of their disease is significant. The Internet is also becoming increasingly important as a source of cancer-related information for patients. Previous studies have reported that Internet use was associated with greater awareness of genetic testing among women with a family history of breast or ovarian cancer (Meischke et al. 2001), and that greater trust of health information from the Internet was associated with greater clinical trial awareness among respondents to the Health Information National Trends Survey (Langford et al. 2010). A study by Gray et al. (2009) suggested that among patients with colon cancer, those who reported having sought information from physicians and the Internet were more likely to have heard of novel targeted therapies, such as bevacizumab and cetuximab, and patients who sought information from physicians/other health professionals were more likely to have received bevacizumab or cetuximab (Gray et al. 2009). Furthermore, Castleton et al. (2010) reported that 13.3 % of patients had treatment-related decisions influenced or changed by information they found on the Internet. These results suggest that patients who used the Internet did so because they were seeking information about clinical trials or had a better understanding of research biopsies. The results of our study further suggest that novel sources of information, such as the Internet, may contribute to patients’ willingness to undergo biopsies.
Lower anxiety prior to previous biopsies was also associated with a greater willingness to provide an optional or more than one biopsy. Music therapy has been used previously to ameliorate anxiety and pain levels in patients undergoing biopsy (Shabanloei et al. 2010). Willingness to undergo an optional biopsy was associated with a higher likelihood of having undergone a previous biopsy, suggesting that patients who have had a previous biopsy are more willing to undergo biopsies subsequently.
Of interest, the most common reason not to undergo biopsies patients’ beliefs that it would not help the management of their cancer. Further, the most common reason for willingness to undergo more than one biopsy was only if the information provided would be useful to inform their treatment options. These data suggest that altruism may not be a primary driver of undergoing research biopsies.
Dissent has been expressed regarding the ethics of research biopsies, especially with regard to potential harm without direct benefit to patient care (Helft and Daugherty 2006). However, a study by El-Osta et al. (2011) demonstrated that single and repeated/sequential research biopsies obtained in phase 1 clinical trials were safe, with very low levels of risk of serious complications (1.5 %).
A unique feature of the present study was that participants were recruited from an actual phase 1 clinical trial patient population. This contrasts with earlier studies in which most respondents were not necessarily participants in cancer clinical trials and included mostly patients from ambulatory medical oncology cancer clinics (Agulnik et al. 2006). Also, to our knowledge, the present study is the first to examine factors related to biopsy willingness among phase 1 clinical trial participants in a US setting. A limitation of the present study was that the survey instrument we designed and used to generate our data has not been separately validated. However, sections of this instrument, particularly questions relating to demographics and quality of life, have been used previously among the phase 1 population in our clinic (Naing et al. 2011).
The existing literature on biopsy willingness among cancer patients is inconclusive. Previous studies revealed that some patients believed that consenting to a biopsy procedure would improve their health care despite being told that the biopsies were purely for research purposes (Agulnik et al. 2006). Conversely, some patients were willing to accept biopsy procedures as a gold standard of early phase clinical trials knowing that it would benefit the scientific community (Park et al. 2004). The present study sheds light on the deciding factors in a clinical trial subject’s decision to participate in a study-related biopsy procedure and can help to identify patients who may be willing to undergo a biopsy. Such information can be used to modify the informed consent process to increase enrollment of patients who are willing to provide biopsies.
In conclusion, our results suggest that stated willingness to undergo biopsy is more common among men and in patients who use the Internet as a source of information. Furthermore, patients were more willing to undergo one or more biopsies if the results were relevant to their disease. Patients who used the Internet as a source of cancer-related information were more willing to give biopsies, suggesting that a lack of access to information among patients who are not Internet users may decrease biopsy willingness. In response to the findings of the present study, our department has instituted ongoing education for patients in the phase 1 clinic. The course is conducted by mid-level health care personnel and educates patients on the requirements of phase 1 clinical trials in general and touches on the importance of research biopsies in particular.
Acknowledgments
We thank Joann Aaron, MS, Scientific Editor, Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, for scientific editing of the manuscript.
Conflict of interest
The authors declare no conflict of interest.
References
- Agulnik M, Oza AM, Pond GR, Siu LL (2006) Impact and perceptions of mandatory tumor biopsies for correlative studies in clinical trials of novel anticancer agents. J Clin Oncol 24(30):4801–4807. doi:10.1200/jco.2005.03.4496 [DOI] [PubMed] [Google Scholar]
- Bernhard J, Dietrich D, Glimelius B, Hess V, Bodoky G, Scheithauer W, Herrmann R (2010) Estimating prognosis and palliation based on tumour marker CA 19–9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy. Br J Cancer 103(9):1318–1324. doi:10.1038/sj.bjc.6605929 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Castleton K, Fong T, Wang-Gillam A, Waqar MA, Jeffe DB, Kehlenbrink L, Gao F, Govindan R (2010) A survey of internet utilization among patients with cancer. Support Care Cancer. doi:10.1007/s00520-010-0935-5 [DOI] [PubMed] [Google Scholar]
- Chabner BA (2010) New results will change the paradigm for phase 1 trials and drug approval. Oncologist 15:1023–1025 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crook JM, Gomez-Iturriaga A, Wallace K, Ma C, Fung S, Alibhai S, Jewett M, Fleshner N (2011) Comparison of health-related quality of life 5 years after SPIRIT: surgical prostatectomy versus interstitial radiation intervention trial. J Clin Oncol 29(4):362–368 [DOI] [PubMed] [Google Scholar]
- Dowlati A, Haaga J, Remick SC, Spiro TP, Gerson SL, Liu L, Berger SJ, Berger NA, Willson JK (2001) Sequential tumor biopsies in early phase clinical trials of anticancer agents for pharmacodynamic evaluation. Clin Cancer Res 7(10):2971–2976 [PubMed] [Google Scholar]
- Eisenhauer EA, Twelves C, Buyse M (2006) Phase 1 Cancer Clinical Trials: A Practical Guide. Oxford University Press Inc., New York [Google Scholar]
- El-Osta H, Hong D, Wheeler J, Fu S, Naing A, Falchook G, Hicks M, Wen S, Tsimberidou AM, Kurzrock R (2011) Outcomes of research biopsies in phase 1 clinical trials: the MD anderson cancer center experience. Oncologist 16(9):1292–1298 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O’Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363(9):809–819 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gray SW, Armstrong K, Demichele A, Schwartz JS, Hornik RC (2009) Colon cancer patient information seeking and the adoption of targeted therapy for on-label and off-label indications. Cancer 115(7):1424–1434. doi:10.1002/cncr.24186 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Helft PR, Daugherty CK (2006) Are we taking without giving in return? The ethics of research-related biopsies and the benefits of clinical trial participation. J Clin Oncol 24(30):4793–4795. doi:10.1200/jco.2006.05.7125 [DOI] [PubMed] [Google Scholar]
- Izzedine H, Isnard-Bagnis C, Launay-Vacher V, Mercadal L, Tostivint I, Rixe O, Brocheriou I, Bourry E, Karie S, Saeb S, Casimir N, Billemont B, Deray G (2006) Gemcitabine-induced thrombotic microangiopathy: a systematic review. Nephrol Dial Transplant 21(11):3038–3045. doi:10.1093/ndt/gfl507 [DOI] [PubMed] [Google Scholar]
- Jimenez-Gordo AM, Feliu J, Martinez B, de-Castro J, Rodriguez-Salas N, Sastre N, Vilches Y, Espinosa E, Rodriguez-Aizcorbe JR, Gonzalez-Baron M (2009) Descriptive analysis of clinical factors affecting terminally ill cancer patients. Support Care Cancer 17(3):261–269. doi:10.1007/s00520-008-0460-y [DOI] [PubMed] [Google Scholar]
- Kluger HM, Dudek AZ, McCann C, Ritacco J, Southard N, Jilaveanu LB, Molinaro A, Sznol M (2011) A phase 2 trial of dasatinib in advanced melanoma. Cancer 117(10):2202–2208. doi:10.1002/cncr.25766 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363(18):1693–1703. doi:10.1056/NEJMoa1006448 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Langford A, Resnicow K, An L (2010) Clinical trial awareness among racial/ethnic minorities in HINTS 2007: sociodemographic, attitudinal, and knowledge correlates. J Health Commun 15(Suppl 3):92–101. doi:10.1080/10810730.2010.525296 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maida V, Peck J, Ennis ME, Brar N, Maida AR (2010) Preferences for active and aggressive intervention among patients with advanced cancer. BMC Cancer 10:1–10 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mego M, De Giorgi U, Dawood S, Wang X, Valero V, Andreopoulou E, Handy B, Ueno NT, Reuben JM, Cristofanilli M (2011) Characterization of metastatic breast cancer patients with nondetectable circulating tumor cells. Int J Cancer 129(2):417–423. doi:10.1002/ijc.25690 [DOI] [PubMed] [Google Scholar]
- Meischke H, Bowen D, Kuniyuki A (2001) Awareness of genetic testing for breast cancer risk among women with a family history of breast cancer: effect of women’s information sources on their awareness. Cancer Detect Prev 25(4):319–327 [PubMed] [Google Scholar]
- Naing A, Stephen SK, Frenkel M, Chandhasin C, Hong DS, Lei X, Falchook G, Wheler JJ, Fu S, Kurzrock R (2011) Prevalence of complementary medicine use in a phase 1 clinical trials program. Cancer 117:5142–5150 [DOI] [PubMed] [Google Scholar]
- Park JW, Kerbel RS, Kelloff GJ, Barrett JC, Chabner BA, Parkinson DR, Peck J, Ruddon RW, Sigman CC, Slamon DJ (2004) Rationale for biomarkers and surrogate end points in mechanism-driven oncology drug development. Clin Cancer Res 10(11):3885–3896. doi:10.1158/1078-0432.ccr-03-0785 [DOI] [PubMed] [Google Scholar]
- Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3(75):75ra26. doi:10.1126/scitranslmed.3002003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shabanloei R, Golchin M, Esfahani A, Dolatkhah R, Rasoulian M (2010) Effects of music therapy on pain and anxiety in patients undergoing bone marrow biopsy and aspiration. AORN J 91(6):746–751. doi:10.1016/j.aorn.2010.04.001 [DOI] [PubMed] [Google Scholar]
- Sherrill B, Amonkar MM, Sherif B, Maltzman J, O’Rourke L, Johnston S (2010) Quality of life in hormone receptor-positive HER-2 + metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib. Oncologist 15(9):944–953 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stewart DJ, Kurzrock R (2009) Cancer: the road to amiens. J Clin Oncol 27:328–333 [DOI] [PubMed] [Google Scholar]
- Yu EY, Wilding G, Posadas E, Gross M, Culine S, Massard C, Morris MJ, Hudes G, Calabro F, Cheng S, Trudel GC, Paliwal P, Sternberg CN (2009) Phase II study of dasatinib in patients with metastatic castration-resistant prostate cancer. Clin Cancer Res 15(23):7421–7428. doi:10.1158/1078-0432.ccr-09-1691 [DOI] [PMC free article] [PubMed] [Google Scholar]