Integrating Tobacco Treatment Into Cancer Care: A Randomized Controlled Comparative Effectiveness Trial
Phase: NA
Conditions: Smoking Cessation
Sponsor: Massachusetts General Hospital

1 
 
Integrating Tobacco Treatment Into Cancer Care: A Randomized Controlled 
Comparative Effectiveness Trial 
 
NCT01871506 
 
05/10//2016 
 
 

2 
 
 
Integrating Tobacco Treatment into Cancer Care: 
Study Protocol for a Randomized Controlled Comparative Effectiveness Trial 
 
 
Authors 
 
* Elyse R. Park, PhD, MPH 1,2,6,7  – epark@mgh.harvard.edu 
Jamie S. Ostroff, PhD 3 – ostroffj@mskcc.org 
Giselle K. Perez, PhD 1,6,7  – gperez@mgh.harvard.edu 
Kelly A. Hyland, BA 4 – khyland@mail.usf.edu 
Nancy A. Rigotti, MD 1,2,9 – nrigotti@partners.org 
Sarah Borderud, MPH 3 – borderus@mskcc.org 
Susan Regan, PhD 1 – sregan@mgh.harvard.edu 
Alona Muzikansky, MA 5 – amuzikansky@mgh.harvard.edu 
Emily R. Friedman, BA 1, 6 – erfriedman@mgh.harvard.edu 
Douglas E. Levy, PhD 1 – dlevy3@mgh.harvard.edu 
Susan Holland, MA 3 – hollands@mskcc.org 
Justin Eusebio, BA, MA 6 – jeusebio@mgh.harvard.edu 
Lisa Peterson, BS 3 – petersol@mskcc.org 
Julia Rabin, BA 1,6  – jtrabin@mgh.harvard.edu 
Jacob Miller-Sobel, BS 3 – millersj@mskcc.org 
 
Irina Gonzalez, MD 7 – igonzalez4@mgh.harvard.edu 
Laura Malloy, LICSW 8 – lmalloy@mgh.harvard.edu 
Maureen O’Brien, RN, MS 3 – obrienm@mskcc.org 
Suhana de León-Sanchez, RN, NP 3 – deleonss@mskcc.org 
C. Will Whitlock, RN, NP 3 – whitlocc@mskcc.org 
 
 
1 Mongan Institute for Health Policy, Massachusetts General Hospital, Boston, MA 
2 Tobacco Research and Treatment Center, Massachusetts General Hospital, Boston, MA 
3 Department of Psychiatry & Behavioral Sciences, Tobacco Treatment Program, Memorial Sloan Kettering 
  Cancer Center, New York, NY 
4 H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 
5 Biostatistics Center, Massachusetts General Hospital, Boston, MA 
6 Cancer Outcomes Research Program, Massachusetts General Hospital, Boston, MA 
7 Department of Psychiatry, Massachusetts General Hospital, Boston, MA 
8 Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Boston, MA 
9 Department of Medicine, Harvard Medical School, Boston, MA 
  
* Indicates corresponding author 
 
 
 
 
 

3 
 
Abstract 
Background: Despite the well-established risks of persistent smoking, 10-30% of cancer patients continue to 
smoke after diagnosis. Evidence based tobacco treatment has yet to be integrated into routine oncology care. 
The study protocol paper describes the manualized treatment interventions, evaluation plan, and overall study 
design of comparing the effectiveness and cost of two treatments across two major cancer centers.   
Methods/Design: A two-arm, two-site randomized controlled comparative effectiveness trial is testing the 
hypothesis that an Intensive Counseling (IC) intervention is more effective than a Standard Care (SC) intervention 
in helping recently diagnosed cancer patients quit cigarette smoking.  Both interventions include 4 weekly 
behavioral counseling sessions and a recommendation for use of FDA-approved smoking cessation medication. 
The IC intervention condition includes an additional 4 biweekly and 3 monthly counseling sessions as well as 
dispensal of the recommended FDA-approved smoking cessation medication at no cost. The trial is enrolling 
patients with suspected or newly diagnosed cancer who have smoked a cigarette in the past 30 days. Participants 
are randomly assigned to receive the SC or IC intervention. Tobacco cessation outcomes are assessed at 3 and 
6 months. The primary study outcome is 7-day point prevalence biochemically validated tobacco abstinence. 
Discussion: This trial will answer key questions about delivering tobacco treatment interventions to newly 
diagnosed cancer patients. If found to be efficacious and cost effective, this treatment will serve as a model to be 
integrated into oncology care settings nation-wide, as we strive to improve treatment outcomes and quality of life 
for cancer patients. 
 
 
Key Words: Smoking Cessation, Tobacco Treatment, Cancer Patients, Randomized Controlled Trial, 
Motivational Interviewing, Pharmacotherapy 
 
 

4 
 
Integrating Tobacco Treatment into Cancer Care: Study Protocol for a Randomized Controlled 
Comparative Effectiveness Trial 
 
Introduction 
           Smoking is responsible for approximately one in five deaths each year in the United States [1,2].  Thirty 
percent of cancer deaths in the United States in 2015 will be caused by tobacco use [3]. Persistent smoking 
following a cancer diagnosis is associated with diminished effectiveness of cancer treatment, increased risks of 
recurrence and second primary cancer diagnoses [4-10], decreased overall  survival [11-14],  diminished quality 
of life [11,15,16], and increased complications from surgery, radiation, and chemotherapy [17-23]. 
 
Despite the risks of persistent smoking, approximately 10% to 30% of cancer patients continue to smoke 
after a cancer diagnosis [11, 24-26]. Studies utilizing national datasets, have shown that approximately 1 in 10 
cancer survivors smoke [27-29]. Currently, tobacco treatment is not well-integrated into cancer care. Several 
leading oncology organizations have identified this as a missed opportunity for addressing this important 
modifiable behavior associated with poorer cancer outcomes [30-32], however, many cancer patients who smoke 
are not asked about their smoking status, are not advised to quit [33, 34], and do not get proper assistance to quit 
or stay quit [35, 36]. These findings are notable, as many cancer patients who smoke want to quit smoking [37-
41]. A recent prospective study among participants from the Cancer Prevention Study-II Nutrition Cohort reported 
high rates of quitting behavior among smokers with cancer in the 2-4 years following a cancer diagnosis [14].  
Patient, physician and system level factors impede the delivery of effective tobacco cessation programs during 
cancer care [35, 42-44]. Only half of NCI-designated comprehensive cancer centers, in 2009, had any type of 
tobacco treatment program [45]. 
The 2008 U.S. Public Health Service Treating Tobacco Use and Dependence Clinical Practice Guideline 
(PHS) recommends that evidence-based tobacco treatment,  including combined medication and multiple 
counseling sessions, be delivered to all smokers in health care settings [46]. Unfortunately, little progress has 
been made with integrating these guidelines into cancer care settings. With few exceptions [47], smoking 
cessation studies with cancer patients have been limited by very small sample sizes and delayed tobacco 
treatment initiation [48]. It is critical to start tobacco treatment as close to the time of diagnosis as possible, since 
the closer cessation is to the time of diagnosis, the higher the likelihood for continued abstinence [11, 37, 38, 49, 
50] which, in turn, improves cancer treatment outcomes.  

5 
 
 
Thus, the primary study aim is to compare the effectiveness of two tobacco treatments integrated into 
cancer care in producing tobacco abstinence at 6 months. We hypothesize that the IC will significantly increase 
the proportion of smokers with biochemically-confirmed, 7-day point-prevalence tobacco abstinence at 6 months 
compared to the SC. Secondary aims are to: a) explore mechanisms through which each treatment promotes 
abstinence; b) understand variations in abstinence outcomes by subpopulation; c) examine components of 
treatment that promote abstinence; and d) identify the percentage and associated characteristics of smokers who 
enroll and adhere to tobacco treatment. Lastly, we will compare the cost per quit within each treatment group. 
 
 
 
Design and Methods 
 
Study design 
The Smokefree Support Study is an ongoing two-site, randomized controlled trial comparing the 
effectiveness of an Intensive Counseling (IC) versus Standard Care (SC) in helping recently diagnosed cancer 
patients become smokefree.  
  
Conceptual framework 
 In order to guide the development of a tobacco treatment intervention in the context of a cancer 
diagnosis, we combine a coping with illness model and a health behavior change model. The Self-Regulation 
Model (SRM), a framework widely used to study patients’ coping with cancer [51, 52], focuses on the dynamic 
process between beliefs, emotions and coping. It postulates that individuals form illness representations (e.g., 
What is it?) that guide their behavioral responses to an illness and then engage in strategies (e.g., What can I do 
that will make me feel better?) to reduce distress. Illness representations can be influenced by environmental 
(e.g., others’ smoking in the home) and physical (e.g., shortness of breath) factors. Parallel processing between 
illness beliefs and emotions leads to a coping response (e.g., quitting) and subsequent monitoring of the success 
of coping efforts. Applying the SRM to a cancer diagnosis: Changes in beliefs about cancer outcomes (e.g., 
quitting smoking reduces risk of treatment complications) may lead to engagement in quitting as a strategy to 
cope with the cognitive and emotional threat of cancer. Furthermore, if individuals’ evaluation of the effects of 
quitting, physical changes (e.g., breathing and pain have improved), and environmental influences (people are no 
longer smoking in their home) make them feel better, then they will be more likely to stay quit. If quitting smoking 

6 
 
decreases an individual’s sense of shame and related anxiety, this will increase the chances that he/she will stay 
quit. The Health Belief Model (HBM) [53] has been widely used to study smoking cessation, and it focuses on 
health beliefs that underlie behavior change. The HBM posits that when faced with a health threat, individuals are 
more likely to change a behavior if they feel the threat is serious, they are at risk, they are able to make the 
change, and the change would decrease their risk. Applying the HBM to a cancer diagnosis: Smokers will be 
more likely to engage in tobacco treatment and quit if they 1) believe that continued smoking after a cancer 
diagnosis is a serious threat to their health; 2) understand that continuing to smoke puts them at risk for poor 
outcomes (i.e., treatment complications, cancer recurrence); 3) are confident that they can quit; and 4) believe 
that quitting will reduce their risk of poor outcomes. 
 
Setting  
Participants are being recruited from two academic medical centers - the Massachusetts General Hospital 
(MGH) Cancer Center located in Boston, MA and the Memorial Sloan Kettering Cancer Center (MSKCC) located 
in New York City, NY.  This trial is currently open to enrollment and began enrolling subjects in November of 
2013. 
 
Inclusion/Exclusion criteria 
Study inclusion and exclusion criteria are detailed in Table 1.  In brief, adult cancer patients who are 
identified as current smokers and are undergoing cancer treatment at MGH or MSKCC, have phone access, and 
are English and Spanish (MGH only) speaking are eligible for study participation. Criteria have been selected to 
be as inclusive as possible. Of note, patients are eligible if they are willing to discuss changing their smoking 
behavior; patients are not required to be willing to quit upon enrollment. Patients with psychiatric disorders are 
eligible as long as there are no indications of current uncontrolled illness. Advanced stage of disease is not an 
exclusion criterion unless it is determined by an oncology clinician that the patient is medically unable to 
participate.  
 
 
 
 

7 
 
 
Table 1.        Study inclusion and exclusion criteria 
 
Inclusion criteria 
• 
New* patient, opting to receive cancer care at a participating cancer center 
• 
• 
Suspected or newly diagnosed thoracic, breast, genitourinary, gastrointestinal, head/neck, lymphoma, melanoma or gynecological 
cancer 
• 
Age ≥18 years 
English or Spanish speaking (MGH only) 
• 
Has smoked a cigarette, even a puff, in the last 30 days 
• 
Willing to consider trying to quit smoking 
Exclusion criteria 
• 
Non-English or non-Spanish speaking  
• 
No regular access to telephone 
• 
Medically ineligible  (ECOG >2, active dementia, referral to hospice care, or too sick to participate as determined by the treating 
oncology clinician or study investigators) 
• 
Current, active, untreated psychiatric illness (bipolar disorder, manic-depressive disorder, schizophrenia, schizoaffective disorder, or a 
psychotic disorder) 
• 
Suicidal ideation-related hospitalizations within the past year   
• 
Endorsement of current suicidal intent 
• 
No intention to receive cancer care at a participating cancer center 
• 
 Insufficient literacy or comprehension 
• 
 MSKCC only: Already receiving tobacco treatment through the existing TTP service 
*Patient is attending approximately one of their first 4 visits or are within 3 months of their initial visit date with their primary oncologist at a 
participating institution.  Additionally, patients will be considered new if they 1) are seeking a second opinion and are opting to receive cancer 
care at a participating institution; 2) have local and distant recurrence of tumors with past cancers diagnoses; or 3) are diagnosed with a new 
form of cancer other than a previously treated type of cancer. 
 
 
Recruitment 
           Eligible patients are identified and recruited by distinct mechanisms at the two participating institutions: The 
MGH in Boston, MA and the MSKCC in New York City, NY. 
MGH. Potential participants are identified using multiple recruitment approaches, including 1) collection of 
a smoking status intake form; 2) screening of daily clinic patient lists; and 3) direct provider referrals. Specifically, 
new patients attending an MGH clinic in the thoracic, gastrointestinal (GI), genitourinary (GU), breast, head/neck, 
lymphoma, gynecological, or melanoma disease center answer a 2-question smoking status screener with 
multiple choice response options to the questions: “Do you now smoke cigarettes every day, some days or not at 
all?”, and “About how long has it been since you last smoked a cigarette, even a puff?” Screener questions are 
included on written clinic intake forms, attached as a stand-alone form in new patient charts or administered by a 
research staff member. Hard copy forms are collected daily, reviewed, and entered into a screening database by 
the study Research Assistant (RA). Potentially eligible patients are further identified from new patient lists 
circulated by each disease center as well as from oncologist referrals. A full electronic medical record review is 
conducted on patients with newly diagnosed or suspected cancer who report having smoked a cigarette, even a 
puff, in the prior month and who are > 18 years of age. Full electronic medical record review includes screening 

8 
 
for all eligibility criteria, as appears in Table 1.  If a patient is deemed eligible based on the electronic medical 
record review, a member of the patients’ oncology care team is contacted to confirm medical eligibility and study 
suitability as well as obtain permission to introduce the study to the patient. For patients with an upcoming visit 
scheduled to the cancer center, a member of the research staff visits the patient during their appointment to 
introduce the study and provide a study information flyer.  A patient can then decide at that time to enroll, refuse, 
or request to be contacted at a later date by a research staff member. 
 
For patients who do not have an appointment scheduled for the near future, research staff mails a study 
information flyer and an opt-out letter co-signed by the study principal investigator (PI) and the study clinic liaison. 
The opt out letter instructs patients to contact research staff, via telephone number or email, within 7 days of 
receipt of the letter if they do not wish to participate. If a patient does not contact the research staff within 7 days, 
then a research team member calls the patient to discuss study participation. 
 
MSKCC. Eligible patients at MSKCC are identified through either 1) routine referrals to the Tobacco 
Treatment Program (TTP) or 2) clinic-based identification of smokers in the outpatient thoracic, GI, GU, breast, 
head/neck, lymphoma, gynecological, and melanoma clinics.  At MSKCC, it is the standard of care for all patients 
to be screened for smoking status (e.g., In the past 30 days, have you smoked cigarettes or used any other forms 
of tobacco [cigars, pipe, smokeless tobacco, electronic cigarettes]?), and patients who report current tobacco use 
(i.e., every day or some days) are automatically referred to the MSKCC TTP. MSKCC research staff screen the 
electronic medical records of all patient referrals to determine study eligibility; subsequently, all eligible patients 
are mailed an introductory letter that briefly explains the study and provides the RA’s contact information so that 
they may contact the research team member to opt in or out of the study. The MSKCC tobacco treatment 
specialist (TTS) attempts to reach each eligible referral three times. If the TTS is unable to reach the patient, an 
RA makes three additional contact attempts (phone or face-to-face in clinic).   
As stated above, patients are also recruited face to face through the MSKCC outpatient thoracic, GI, GU, 
breast, head/neck, lymphoma, gynecological, and melanoma clinics. To aid the physicians in identifying eligible 
participants, the clinic-designated RA reviews the daily clinic roster to identify patients who may be eligible for 
study participation.  S/he then contacts the patient’s physician either via e-mail and/or face to face in clinic so as 
to prompt the physician of the potential eligibility of this patient for study participation. The physician then confirms 
eligibility and advises the RA of when best to approach the patient for possible consent to this study.  After 

9 
 
receiving physician approval, the RA approaches newly identified smokers as well as follow-up patients referred 
to the TTP who have not been reachable by phone.  Potentially eligible patients who are approached in clinic are 
provided a study information sheet. All patients who express interest in study participation are asked to complete 
an eligibility screener with the RA before beginning consent procedures. 
 
Enrollment 
 In order to minimize patient burden, consent and baseline procedures are typically scheduled in 
conjunction with an upcoming oncology visit. If a patient is unable to sign consent at the time of approach, a future 
appointment is scheduled with the patient to complete consent and baseline study procedures with the RA. 
Consent procedures are also completed via phone, followed by mailed consent, for patients who may not have 
upcoming appointments.  
 
Assignment to treatment group  
Participants are randomly assigned in a 1:1 fashion to 
either the SC or IC treatment arm using a computer-generated 
schedule of randomization IDs and treatment assignments in 
blocks of 6, stratified by study site and tumor type. After 
completing informed consent and baseline assessment 
procedures, the initial counseling session is scheduled to take 
place either in person or by telephone. Randomization to 
treatment arm occurs toward the end of the initial session, prior to 
discussion of cessation medication, when the TTS opens the 
assigned opaque, sealed randomization envelope.  Both patients 
and the TTS remain blinded to study assignment until this point.  
 
Tobacco treatment interventions 
Prior to receipt of counseling, all participants receive a study folder containing an informational sheet 
summarizing the benefits of quitting smoking for cancer patients, medication instruction sheets for bupropion, 
varenicline, patches and lozenges, a fact sheet outlining the current state of knowledge regarding e-cigarettes, 
and a monthly calendar for participants to monitor and track their cessation medication use.  

10 
 
Participants assigned to the SC group receive a total of 4 cessation counseling sessions plus medication 
advice. Participants randomized to the IC arm receive the same four sessions as the SC group.  In addition, IC 
participants receive (1) extended counseling support and (2) up to 90 days of FDA-approved smoking cessation 
medication at no cost (Figure 1: Study Design). The counseling overview and session topics are shown in Table 
2. Participants may withdraw from trial participation at any time, and they may be withdrawn by the investigators 
in the event of a referral to hospice or declining performance status (ECOG >2). 
 
Counseling session format and content  
All counseling sessions follow a motivational interviewing (MI) style, tailored according to stage of 
readiness. Utilization of an empathic MI style helps patients maintain motivation during a difficult time, such as 
initiating cancer treatment. MI is a particularly salient strategy for newly diagnosed cancer patients for several 
reasons: First, MI focuses on building and 
maintaining self-confidence, and our pilot work 
showed that this population reports low 
confidence; Secondly, the main MI tools (open-
ended questions, affirmations, reflections, and 
summarizing statements) are effective when 
addressing sensitive topics, such as cancer and 
smoking-related beliefs (e.g., shame, fear of 
recurrence) and in delivering smoking 
information (e.g., risk/benefits of quitting in 
relation to cancer treatment). MI also utilizes a 
sensitive and effective strategy, known as “Elicit 
Provide Elicit,” to convey health benefits [54]. 
Finally, MI skills can be used to encourage and 
sustain quit motivation by eliciting ideas and 
forming action plans, such as how to cope with 
cravings, cancer treatment or medication effects, 
adhere to medications, create smoke-free 
Standard of Care 
Intensive Treatment 
Session 
# 
Counseling Focus 
1 
Weekly 
• Smoking assessment  
• Barriers to quitting and strategies to enhance 
readiness 
• Medication education and assistance 
2 
• Cancer related care and distress, care team 
communication 
• Assess medication adherence and managing side 
effects 
• Knowledge about quitting at the time of diagnosis 
3 
• Coping with cravings and withdrawal 
• Introduction to social support 
4 
• Introduction to Stress management – deep breathing 
exercises 
 
5 
Bi-weekly 
• Introduce beginning with appreciations 
• Values clarification exercise 
• Smokefree home and car 
• Nicotine and addiction 
6 
• Smoking associated stigma and negative self-talk 
• Stress management 2 – battery exercise 
• Weight gain concerns 
• Review values clarification exercise 
7 
• Risk of other forms of tobacco 
• Types of social support 
• Stress management 3 – stress signs and coping 
8 
• Rewards and pleasurable activities 
• Sleep and self-care 
• Breath awareness 
9 
Monthly 
• Fear of recurrence 
• Managing physical symptoms 
• Stress management 4 – single pointed focus exercise 
10 
• Financial costs of smoking 
• Managing slips and relapses during/following 
treatment 
11 
• Review overall smoking progress 
• Finalize smoking goals, relapse prevention 
• Post treatment support 
Table 2.   Counseling Overview 
 

11 
 
homes, and learn mood management strategies.  
The counseling session format is structured around the 5As format (Table 3), standardized, and tailored 
based on motivation to quit. The TTS Asks participants about their smoking status and progress; Advises 
participants to quit; Assesses participants’ motivation, confidence, and readiness to quit; Assists participants in 
making a quit plan while addressing medication dosing and side effects; and Arranges for follow-up by 
summarizing the treatment plan and emphasizing treatment adherence. The first four counseling sessions occur 
weekly over a one-month period, and participants have the option to complete sessions in-person in coordination 
with their treatment schedule, or by phone.  Participants may call or email the TTS if questions arise between 
sessions. All sessions close with a summary of session content and participant goals, a recap of participants’ 
reasons for quitting/cutting back, a plan for the next call, and a reminder of assigned homework. The TTS 
documents each session in the electronic health record (EHR). 
Table 3.      Counseling session format 
 
Initial counseling session. The initial counseling session lasts approximately 40 minutes.  During this 
session, the TTS: 1) introduces the study, and provides an overview of the goals and structure of the program; 2) 
gathers a comprehensive smoking history, including past quit attempts and medication trials; 3) assess 
participants’ concerns about smoking; 4) summarizes information gleaned and offers a personalized message to 
quit smoking; 5) assesses participants’ importance and confidence to quit as well, as their pros and cons for 
quitting and continuing to smoke; and 6) evaluates participants’ readiness to quit.  For participants who are not 
ready to quit or make changes, the TTS focuses on addressing ambivalence and increasing motivation to quit by 
helping participants identify their specific barriers to quitting and by encouraging participants to keep a daily diary 
of their smoking rate and pattern. Keeping in line with MI principles, the TTS utilizes a patient-centered approach 
with setting cessation goals and does not counter resistance to quitting or making changes. The TTS tailors 
participants’ quit plan based on their quit stage, which falls into one of 3 branching logics: 1) not ready to quit or 
5As 
Topics 
Ask  
Explore smoking history 
Advise 
Discuss the importance of quitting smoking in the context of a cancer diagnosis, benefits of quitting smoking prior to 
cancer treatment, and protecting self and loved ones from second hand smoke exposure (SHSe) 
Conduct motivational interviewing procedures that focus on decreasing SHSe 
Assess 
Evaluate readiness to quit (quitting importance and self-efficacy while facing a cancer diagnosis) using baseline 
survey responses  
Assist 
Make a quit plan in the context of a cancer diagnosis and treatment 
Discuss medication dosing and side effects 
Arrange 
Follow-up with summary of treatment plan and emphasize adherence to treatments 

12 
 
make changes; 2) not ready to quit, but ready to make changes; and 3) ready to quit.  For participants who are 
not ready to quit but are willing to make changes, the TTS offers additional strategies, including assisting with 
different approaches to cutting back and creating a smokefree home/car.  Participants who are ready to quit are 
offered each strategy aforementioned; in addition, they are assisted with setting a quit date and taking appropriate 
steps to prepare to quit.  The TTS also discusses strategies to cope with cravings.  The TTS assists the 
participant in setting a goal for the week and schedules a follow-up session for the next week.   
Medication advice. Regardless of quit stage, all participants are offered medication advice to assist 
cessation efforts. A participant’s medical history, prior quit and smoking cessation medication experiences, as well 
as attitudes toward medication, are considered when making medication recommendations. The TTS provides a 
general overview of the function, limitations, risks and benefits and usage guidelines for FDA-approved 
medications, and they use a Cessation Medication Decision Aid flowsheet to guide medication recommendation 
based on participants’ history and preference. Subsequently, the TTS offers assistance with obtaining medication 
for patients who express interest. In order to facilitate communication with other providers, the TTS documents 
their medication recommendation as well as patients’ preferences and interests in taking any of the smoking 
cessation medications in the patient’s EHR. 
Weekly follow-up counseling sessions. Following the initial counseling session, participants are offered 
3 weekly proactive follow-up sessions. Sessions follow a similar format as the initial visit, wherein the TTS checks 
in on participants’ smoking progress, cancer care status, level of quit confidence and importance, and level of 
distress.  Further, the TTS assesses and intervenes on the use of cessation medications; specifically, the TTS 
monitors adherence, problem-solves barriers to medication use, and addresses medication concerns and side 
effects. Session time is also spent reviewing progress on goals set, which the TTS uses to help participants’ 
reflect on content discussed in prior sessions. Session-specific modules are introduced to briefly discuss and 
assist with themes often impacting cessation behavior, such as stress and social support. Further tailoring of 
treatment occurs when the TTS checks in on quitting goals and targets their action plan based on participants’ 
quit stage, which falls into one of four quitting goal branches: 1) does not want to quit; 2) now wants to quit or has 
tried to quit; 3) has quit but experienced lapse or relapse; and 4) has quit and stayed quit.  Each branching logic is 
designed to meet participants where they are in terms of quit readiness, minimizing confrontation and maximizing 
intervention points based on their level of motivation to quit and cessation progress. Specifically, the TTS spends 
time assessing barriers to quitting and weighing the pros and cons for participants’ who remain ambivalent; 

13 
 
identifying and assisting with triggers and cravings for participants who are preparing to quit or who have recently 
quit; and assisting with withdrawal symptoms for participants who have quit and may be at risk for relapse. The 
fourth session, the final session for SC participants, closes with a review of goals and accomplishments and a 
referral to the state quitline.  
Extended counseling support.  For the IC group, extended counseling consists of 7 additional 
counseling sessions. Participants receive 4 proactive biweekly sessions delivered over a 2-month period, and 3 
monthly booster sessions; altogether, they receive ongoing counseling over a span of 6 months. The structure of 
each follow-up treatment session mirrors the initial weekly sessions, wherein the TTS assesses quit progress and 
cancer care treatment, examines importance and confidence to quit, monitors and intervenes on medication use, 
and tailors quit advice and strategies based on participants’ quit readiness; however, each session also 
introduces novel topics identified to be relevant concerns among cancer patients who are trying to quit.  
Specifically, the TTS may help participants with the following: 1) evaluation of values in the context of smoking 
behavior; 2) assistance with smoking-associated stigma and negative self-talk; 3) help with stress management, 
including identification of energy-depleting factors and reinforcement of stress-relieving activities; 4) overview of 
the risks of other forms of tobacco use; 5) promote effective use of different sources of support to help cope with 
cancer care and cessation efforts; 6) discuss the utility of reward systems for progressive steps toward quit goal; 
7) assistance with maintaining adequate sleep and other aspects of self-care; 8) managing pain and physical 
symptoms; 9) discussing financial costs of smoking; and 10) preparing for relapse and long-term quit 
maintenance.  All sessions reinforce the import of regular participation in counseling sessions, and all session 
highlight the value of maintaining adherence to cessation medications. All sessions also emphasize the 
importance of helping participants’ identify things they are thankful for (appreciations) in the context of ongoing 
disease and treatment-related stressors and difficulties. 
 
Smoking cessation medication. Participants who are randomized to the IC arm during the initial session 
receive the same information as the SC arm in regards to the risks and benefits of concurrent cessation 
medication use and counseling; however, participants in the IC arm receive an initial 4-week supply of free FDA-
approved smoking cessation medication (varenicline, bupropion sustained release [SR] or nicotine replacement 
therapy [NRT]) of their choice, with the option to renew the medication twice for free for up to 90 days. 
Medications are administered according to the PHS guidelines [46]; specifically, participants opting to use 
varenicline or bupropion SR receive the same dose regardless of smoking level, and NRT dose is adapted to 

14 
 
level of smoking as needed for light smokers. Participants also receive a medication-monitoring calendar to keep 
a log of doses taken while enrolled in the study, to help promote and assist with smoking cessation medication 
adherence. Although participants are not required to select a medication during the initial visit, medication 
planning and problem-solving is revisited at each subsequent session; IC participants have up to 4 weeks to 
decide to initiate medication use and 3 months to change medication type if they do not respond to or tolerate 
their initial medication choice.  Side effects are monitored by the TTS and discussed during weekly group 
supervision with the site PI. 
 
MGH-specific medication dispensing procedures. Prior to dispensing the study medication, the TTS 
contacts the patient’s treating oncologist for their approval and signature. Upon receipt of oncologist approval and 
script, the study site RA mails the study medication to the patient or provides the patient with the medication in-
hand during one of their upcoming clinic appointments. The study psychiatrist reconciles patient medication 
requests within their EMR on a biweekly basis. 
MSKCC-specific medication dispensing procedures. MSKCC clinical research procedures require a 
prescribing clinician to sign consent with each patient for all studies on which prescription medication is made 
available to patients.  Therefore, patients randomized to the IC group who choose to take varenicline or bupropion 
SR are asked to sign an additional consent form at MSKCC.  This consent is obtained by the MSK TTS after 
participants receive their initial counseling session, and it describes the purpose and risks of varenicline and 
bupropion SR use in this study.  The TTSs at MSKCC commonly prescribe cessation medications independently 
within their scope of advanced practice nursing; as such, the MSK TTS also electronically prescribes study 
medications to patients randomized to the IC arm who elect to take cessation medications, and all study 
medications are dispensed from the hospital pharmacy.  Patients with upcoming clinic appointments are able to 
pick up the medications at one of the two out-patient pharmacy dispensaries located on the MSKCC campus; 
alternatively, patients can opt to have the MSKCC pharmacy mail cessation medications to their home addresses.   
 
Quality Assurance   
Our treatment fidelity protocol abides by recommendations of the Treatment Fidelity Workgroup of the 
NIH Behavior Change Consortium (BCC). Specifically, the BCC cites monitoring the following 5 areas to ensure 
that studies reliably and validly test behavioral interventions [55]: 1) Design. We ensure that the treatment-
assigned intervention (counseling and medication dose) is offered to participants through weekly team meetings, 

15 
 
which includes review of TTS documentation; 2) Training. All study TTSs are experienced, certified tobacco 
treatment specialists with expertise in smoking cessation medication and counseling for medical patients. Each 
underwent intensive training in tobacco treatment (including an online course and week-long in-person training 
provided by the Tobacco Treatment Specialist Training and Certification Program at the University of 
Massachusetts Medical School or Rutgers Tobacco Dependence Program), MI skills training, counseling protocol 
training, and specialized didactics on the deleterious health outcomes of smoking for cancer patients and 
managing cancer patients’ distress (e.g., mood & stress management skills). The site PIs have conducted mock 
MI sessions with each tobacco specialist, guided by a modified MI Integrity scoring sheet [56], which includes 
acceptability thresholds [57, 58] to ascertain TTS readiness to begin MI counseling. In addition, to further ensure 
adequate training and protocol preparedness, each TTS listened to supervised cases, practiced each manualized 
session internally and completed 3 pilot cases prior to intervening with study participants. In addition to these 
measures, the TTSs a) meet weekly by phone with Drs. Park and Ostroff for group supervision and b) record all 
counseling sessions, of which 15% are randomly selected and reviewed for adherence by Drs. Park and Ostroff; 
3) Treatment Delivery. For each session, the TTSs document the content covered, participant data (e.g., 
confidence, quit importance), and their impressions (participant’s receptivity); all data are stored in an Access 
database. For suicidality concerns, the study PIs, both licensed clinical psychologists, contact patients to assess 
safety and, if needed, consult with the study psychiatrist and internist regarding significant psychiatric or 
medication concerns; 4) Receipt of treatment. At the end of each session, the TTS summarizes content covered, 
reviews participant goals for tobacco abstinence and medication adherence, and elicits participant’s 
understanding of treatment; and 5) Enactment of treatment skills/knowledge. Participants set treatment goals and 
check-in on their progress during each follow-up session. 
 
Assessments 
           Participants complete assessments three times during the study period, either by mail, electronically 
(through the secure web application, Research Electronic Data Capture [REDCap]), or administered over the 
phone in accordance with their preferences. The baseline survey is completed following informed consent and 
prior to initiating counseling; follow-up surveys are completed 3 and 6-months following baseline survey 
completion. Research staff send three and six-month follow-up survey reminder letters approximately one month 
prior to participants’ survey due date; additionally, they initiate survey outreach attempts (e.g., phone calls, mailed 

16 
 
Table 4.          Data Collection 
and electronic surveys) approximately two weeks prior to the target assessment time point. Participants who 
report smoking abstinence of at least 7 days during the 3 and 6-month follow-up are mailed a saliva collection kit 
with instructions for use and a pre-addressed, pre-stamped return envelope. Saliva samples are then sent to J2 
Laboratories (Tucson, AZ) for cotinine assay.  Participants who report smoking abstinence but would likely have 
elevated salivary cotinine levels due to use of nicotine-based smoking cessation medication or e-cigarettes are 
asked to complete, in-person, an expired air carbon monoxide sample.  Participants are remunerated $20 for the 
baseline survey, $40 for each follow-up survey and $50 for each cotinine or expired air sample provided.  
Participant surveys 
           Data collection includes the following domains:    Sociodemographic questions, including sex, age, 
race/ethnicity, marital/partner status, educational 
attainment, insurance coverage, employment status, 
caretaking responsibilities, language, religious affiliation, 
and family obligation as a perceived referent and support 
system, are collected from the baseline survey and the 
electronic medical record. 
Smoking history. Questions include age at 
smoking initiation, the number of cigarettes smoked per day (historically, and in the past 30 days), number of 
minutes after wake until a cigarette (addiction), date of last cigarette, use of other tobacco products (including 
menthol, pipe, cigar, chewing tobacco, dip snuff, and e-cigarettes), frequency and reason for use of e-cigarettes, 
number of 24-hour quit attempts, longest time without a cigarette, presence of withdrawal symptoms, smoking 
cessation medication use and side effects, and use of alternative methods to help quit smoking (e.g., internet or 
phone-based program, hypnosis). Nicotine dependence is evaluated using a 2-item Heaviness of Smoking Index 
[59]. The index considers the time to first cigarette after waking and the daily consumption of cigarettes.  Scores 
range from 0 to 6 with higher scores indicating higher addiction levels. 
Medical history. A medical record review completed at baseline gathers information about cancer tumor 
types, stage, cancer treatment modality, treatment and diagnosis dates, and comorbid conditions.   
Health Belief and Self Regulation Model Constructs. Emotions: Emotional distress is measured using the 
National Comprehensive Cancer Network (NCCN) Distress Thermometer, a one-item instrument assessing level 
of distress, from 0 or “no distress” to 10 or “extreme distress” in the past two weeks [60, 61]. The Stress Analog 
Variable 
 
EHR 
Participant 
baseline 
survey 
Participant 
follow-up 
survey 
Tobacco 
treatment 
Specialist  
Smoking outcomes 
 
 
x 
x 
Sociodemographics 
x 
x 
 
 
Smoking History 
x 
 
x 
x 
Medical History 
x 
 
 
x 
Emotions 
 
x 
x 
 
Cancer Beliefs 
 
x 
x 
 
Smoking Beliefs 
 
x 
x 
 
Physical Symptoms 
 
x 
x 
 
Environment 
 
x 
x 
x 
Cancer Treatment 
x 
 
 
 
Tobacco Treatment 
 
 
x 
 
Patient Satisfaction 
 
 
x 
 

17 
 
Scale, a one-item instrument, measures participants’ ability to cope with stress, from 0 or “not at all able” to 10 or 
“very much able” in the past two weeks. Anxiety and depression symptoms within the past two weeks are 
assessed using the General Anxiety Disorder Scale (GAD-7) [62] and the Patient Health Questionnaire-9 (PHQ-9) 
[63], respectively. Each are rated on a 4-point Likert scale from “not at all” to “nearly every day.” The Perceived 
Stress Scale-4 (PSS-4) is a four-item generalized measure of the degree to which a respondent appraises 
situations in the past month as stressful [64]. The PSS-4 is scored on a 5-point scale from 0 “never” to 4 “very 
often.”   
Cancer Beliefs – Stigma. The Lung Cancer Stigma scale, a 5-item questionnaire scored on a 5-point 
scale from “strongly disagree” to “strongly agree,” measures the extent to which shame is internalized [65].  
Smoking Beliefs. Readiness to quit smoking is assessed with a one-item,10-point contemplation ladder 
with responses that range from “I enjoy smoking so much I will never consider quitting no matter what happens” to 
“I have quit and I am 100% confident that I will never smoke again” [66]. One item scored on an 11-point scale 
ranging from 0 or “not at all important” to 10 “very important” assesses participants’ perceived importance of 
quitting smoking [67]. Five items scored on an 11-point scale ranging from 0 or “not at all” to 10 or “very much” 
assesses participants’ perceived benefits of quitting smoking as they relate to their perceptions of the severity of 
their cancer, cancer therapy, and risk of recurrence [67]. Self-efficacy to resist smoking urges is assessed with an 
11-item measure scored on an 11-point scale ranging from 0% or “no confidence at all” to 100% or “absolutely 
confident”. Items were adapted from the 46-item Confidence Scale [68].  
Physical Symptoms. Cancer symptom severity over the past two weeks is assessed with three stand-
alone scales for fatigue, pain, and nausea [69]. The items are scored on an 11-point scale ranging from 0 or “no” 
levels of the symptom to 10 or “extreme” levels of the symptom. Sleep is assessed with two stand alone questions 
about hours of actual sleep and sleep quality during the past month [70]. One item is a fill in the blank with 
average hours of sleep per night. The other item is scored on a 1-4 scale ranging from 1 or “very bad” to 4 or 
“very good” overall sleep quality. One item from the Mood and Physical Symptom Scale is used to measure 
participants’ urge to smoke in the past 24 hours [71]. This item is scored on a 6-point scale ranging from 0 or “not 
at all” to 5 or “all of the time.”  
Environmental Influences. Four items evaluate the level of second hand smoke exposure (SHSe) by 
asking participants about the number of people in the household who smoke, the smoking status of their spouse 
or partner, and the rules about smoking in their household and car [72]. Household smoking is scored with one 3-

18 
 
point scale ranging from “no one is allowed to smoke anywhere” to “smoking is permitted anywhere.”  Car 
smoking is scored on a 4-point scale ranging from “no one is allowed to smoke in my car” to “people are allowed 
to smoke in my car at any time.”  Perceived social support is measured using the Partner Interaction 
Questionnaire (PIQ), a 20-item instrument divided into 2 subscales consisting of 10 positive behaviors and 10 
negative behaviors scored on a 5-point scale from 0 or “never” to 4 or “often” [73]. An adapted 8-item instrument 
using 4 positive behaviors and 4 negative behaviors is used in this study.  Four items of the Medical Outcomes 
Study (MOS) Social Support Survey, scored on a 5-point scale from 1 or “none of the time” to 5 or “all of the time” 
[74], are used to explore the types of support that patients with chronic conditions receive from others.  Six items 
were derived from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey 
to assess the quality of the patient experience received from the participants’ oncology care team [75]. Items are 
scored on a 4-point scale from 0 or “never” to 4 or “always”. Seven items were derived from the Department of 
Health and Human Services to assess patient reported oncology provider communication [76]. Items are scored 
on a dichotomous scale of either 0 or “no” or 1 or “yes.”  
 
Quality of Life. The EuroQol 5-Dimensional 5-Level Quality of Life survey (EQ-5D-5L) is a standard 
measure of current health consisting of five dimensions: mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression [77]. Each dimension is rated on a 5-point scale with responses ranging from “no problems” to 
“unable” or “no” to “extremely”. It was specifically designed to facilitate cost analyses. 
 
Cost 
 
Cost-effectiveness will be assessed using cost per quit as the outcome. We will examine the costs of 
implementation were this program to be implemented in a clinical setting; the major costs to be collected include 
training and responsibilities of the TTSs, consulting program physicians and the clinical supervisor, as well as the 
cost of the smoking cessation medications and general program equipment and space (Table 5). 
 
 
 
 
 
 

19 
 
Table 5. Cost data collection domains 
 
 
Outcome Measures 
Intervention effectiveness: Smoking cessation 
 
The primary outcome is verified 7-day point prevalence tobacco abstinence at 6-month follow-up. 
Participants are asked, “in the past 7 days, have you smoked a cigarette, even a puff?”  This is verified by 
biochemically confirmed saliva cotinine (evaluated at both <10 and <15ng/ml), or <10 ppm expired air carbon 
monoxide (CO) for participants concurrently using NRT or e-cigarettes. The secondary outcome measures 
include biochemically confirmed point prevalence abstinence at 3 months, self-report outcomes, significant 
reduction, and 24-hour intentional quit attempts. We chose point prevalence abstinence since it is biochemically 
verifiable and highly correlated with continuous and sustained abstinence [78]. 
Treatment use and adherence 
 
The treatment outcomes may be mediated by factors associated with smoking cessation medication 
usage and treatment adherence.  Secondary outcome measures include: (1) the proportion of participants who 
use smoking cessation medications; (2) duration of medication use measured in number of days; (3) number of 
counseling sessions; and (4) length of counseling sessions.   
 
Tobacco Treatment. Participants are asked about smoking cessation medication use over the past 3 
months, including duration of treatment and side effects, at each of the follow-ups.  Additionally, participants are 
asked about the use of non-study pharmacological and behavioral tobacco treatments (e.g.,nicotine gum, nicotine 
Resource 
Description 
Source of 
resource data 
Source of cost 
data 
 
 
 
 
Tobacco Treatment 
Specialist (TTS) 
Training (tobacco treatment specialist course, basic skills for 
working with smokers online course, motivational interviewing 
training), 
Study records 
Human 
resources data 
 
Supervision (weekly team meetings), 
Intervention delivery (pre-session preparation, cessation 
counseling, EHR note documentation, call attempts, database 
documentation) 
 
 
 
Program Physician(s) 
Medication reconciliation, psychiatric consultation, medication 
side effect consultation 
 
Study records 
Human 
resources data 
Clinical Supervisor and 
Program Director 
Training (motivational interviewing skills, mock cessation 
counseling), treatment fidelity (weekly group supervision 
meetings, review of randomly selected recordings, review of 
randomly selected EHR record documentation) 
Study records 
Human 
resources data 
Smoking Cessation 
Medications 
Up to a 3-month supply of FDA-approved smoking cessation 
medications provided to IC patients 
 
Study records 
Red Book, 2016 
Equipment and Space 
Hospital workspace, telephone use, folders, labels, stickers, 
phone cards, printing costs (paper and ink), mailing costs 
(envelopes and postage) 
Study records 
Study records 

20 
 
nasal spray, nicotine inhaler, quitline, internet program, in-person quit smoking support, text messaging support, 
hypnosis, acupuncture).  Smoking status screening and treatment by oncology providers via the 5As model of 
behavioral change is evaluated by a patient-reported measure consisting of 7 yes-no questions [76] at 3- and 6-
months.  
 
Program Satisfaction 
 
Participant satisfaction with the program is assessed with five multiple choice questions: (1) “To what 
extent has the Smokefree Support Study program met your needs?” (4-point scale ranging from “none of my 
needs have been met” to “almost all of my needs have been met”); (2) Did you get the kind of smoking cessation 
assistance that you wanted? (4-point scale ranging from “no, definitely not” to “yes, definitely”); (3) “How would 
you rate the quality of the smoking cessation assistance that you received?” (4-point scale ranging from “poor” to 
“excellent”); (4) “How helpful has the Smokefree Support Study been for you?” (5-point scale ranging from “not at 
all helpful” to “very helpful”); (5) “If a friend were in need of similar help, would you recommend the Smokefree 
Support Study to him or her?” (4-point scale ranging from “no, definitely not” to “yes, definitely”).  Furthermore, 
participants are asked seven open-ended questions: (1) “What about the Smokefree Support Study did you find 
the most helpful? Why?”; (2) What about the Smokefree Support Study did you find the least helpful? Why?”; (3) 
What were some of the challenges you faced to participating in this program?”; (4) Please list any 
recommendations (e.g., additional topics, skills to include) of how we can improve the Smokefree Support 
Study?”; (5) What other kinds of programs would have been helpful to have around the time of diagnosis?”; (6) 
What kinds of programs would be helpful for you now?”; and (7) “Is there anything else you’d like to tell us?” 
 
 
Data analysis 
Sample size calculations 
           We conservatively estimate a 6-month biochemically-confirmed 7-day point-prevalence tobacco abstinence 
rate of 15% in the SC group and 30% in the IC group [37-39, 79]. With a sample size of 268 participants, 134 in 
each arm, we will have 80% power to detect a difference of 15% with a two-sided significance level of 0.05. We 
conservatively estimate that 10% of participants will die within 6-months of enrollment [80], so an additional 10% 
(n=27) will be recruited. Thus, 295 participants will be needed to have a fully powered trial for the intention-to-treat 
analysis.  

21 
 
  
At the outset, we will examine the frequency distributions of all variables. We will compare the baseline 
characteristics of participants in the two groups. Data from both sites will be pooled for analysis, after confirming 
there is no significant heterogeneity between sites or adjusting as needed. Primary analyses will be intent-to-treat; 
we will classify participants who are lost to follow-up and those who do not provide a self-reported smoking status 
or saliva or air sample as current smokers [81]. In addition, we will determine whether there is differential dropout 
in the two groups and consider developing probability-of-completion weights [82] to obtain unbiased estimates of 
the effect of the treatment.  We will assess whether the mechanism of missing data is missing at random [83]. The 
study results will be submitted for publication and thus available to the public and the medical community upon 
trial completion. 
Aim 1 
 
We will conduct univariate and multivariable analyses to examine the association of treatment group with 
the primary outcome (X→Y)(7-day cotinine confirmed abstinence) and secondary smoking outcomes. We will also 
explore associations between the primary and secondary smoking outcomes. For univariate analyses, we will 
compare the outcomes between the two treatment groups. For multivariable analyses, we will use logistic 
regression models to compare the two groups, adjusting for potential confounding factors. Then, to study the 
intervention effect over the entire follow-up period, we will likely use the Generalized Estimating Equations (GEE) 
approach to include data from both 3-month and 6-month follow-up.  
Aim 2 
 
Aim 2a: We will explore the impact 
of potential mediators of the intervention 
effect (Figure 2: Treatment Model). We will 
test for 1) a significant association between 
treatment and the mediator (X→M) and 2) 
a significant association between the 
mediator and smoking outcome (M→Y) 
(controlling for treatment X) [84]. 
Supplemental to this approach, we will 
potentially use methods (e.g., difference in coefficients method or product of coefficients method) to estimate the 
Figure 2.  Treatment Model 

22 
 
strength of the mediated effect (e.g. partial) [85]. We will likely use the latent-difference-score model, in which 
change in the mediator between the start and end of treatment influences abstinence at 3 months (acquisition of 
abstinence) and 6-months (maintenance of abstinence).  
 
Aim 2b: We will also identify subgroups that experience a greater treatment effect. We will test the 
interaction terms between these variables and treatment assignment in the logistic regression models. Those with 
significant interactions (p<.15) will be considered as candidates for identifying subpopulations.  
 
Aim 2c. We will conduct univariate and multivariable analyses to explore the association of treatment 
utilization on the primary smoking outcome. We will examine the “dose” (medication use and counseling use).  
Medication use and counseling use will potentially be considered as continuous variables and dichotomized 
variables.  We will dichotomize medication and counseling use into two levels: low vs. high. A medication regimen 
completion of >10 weeks would likely be considered as high medication use [86]. From our pilot data, an 
equivalence of ≥8 counseling sessions would likely be considered as high counseling use for IC participants and 
>3 as high for SC participants. For univariate analysis, we will use chi-square tests to compare the primary 
smoking outcome between medication use and counseling use groups.  For multivariable analysis, we will use 
logistic regression models. 
Aim 3 
          Among eligible smokers, we will conduct univariate analyses and a multivariable logistic regression model 
to examine the associations of patient characteristics with enrollment (Y/N). Then, within each treatment group, 
we will determine the association between participant characteristics and treatment utilization. For multivariable 
analysis, we will use linear regression models to determine the effect of participant characteristics, adjusting for 
confounding factors, on treatment utilization. 
 
Data management 
           The master database is located at MGH and was built and tested during Year 1.  Each site has a secure, 
access-restricted MS Access database application for recording recruitment and enrollment data, tracking 
enrolled participants, and entering follow-up survey data. The database is designed to trap data entry errors. 

23 
 
 MSKCC sends its database to MGH on a biweekly basis via an MGH mechanism for securely transferring files. 
The site databases are reviewed following each transfer, and questionable entries are flagged and reported back 
to the site PI and RA.  
The trial is being monitored by a Data Safety and Monitoring Board (DSMB) comprised of five 
independent scientists not otherwise affiliated with the trial. They are experts in the field of oncology, psychiatric 
oncology, smoking cessation and biostatistics. The DSMB meets biannually to review ongoing patient safety, 
important protocol modifications, adverse events and protocol deviations, study progress, and data integrity.  
 
Discussion 
 
Continuing to smoke following a cancer diagnosis may result in poor clinical outcomes. Indeed, the 2014 
Surgeon General’s Report [2] concluded that there is sufficient evidence linking smoking to adverse health 
outcomes in cancer patients. Accordingly, several national organizations, including ASCO and the American 
Association for Cancer Research (AACR), promote incorporating tobacco treatment into the delivery of cancer 
care. However, existing PHS guidelines have yet to be integrated into oncology settings. Thus, we built on 
previous research to compare the effectiveness of integrating two evidence-based tobacco treatments into cancer 
care delivered at two NCI-designated Comprehensive Cancer Centers. This tobacco treatment effectiveness data 
could provide valuable guidance for the advancement and integration of tobacco treatment into cancer care 
settings.  
This paper describes the study design and systems that were created to identify, approach and engage 
cancer patients who smoke in evidence-based tobacco treatment consisting of smoking cessation counseling and 
medication. Moreover, this paper provides detailed information of our treatment integration process and, 
specifically, it outlines methods for accomodating two existing care delivery systems; we provide essential 
information about variations in how patients are identified (e.g., automated versus created system) and 
approached (automated referral versus clinician approval), and we outline different strategies for medication 
dispensing (tobacco treatment specialist with prescription privileges versus treatment specialist without). This 
illustrates potential treatment program modifications that must be considered for broad program implementation. 
This trial assesses the effectiveness of a combination tobacco treatment, consisting of extended 
counseling (11 sessions) plus in-hand FDA-approved medication choice versus standard care (standard 
counseling [4 sessions]) plus advice on FDA-approved medication choice. Our focus on assessing the impact of 

24 
 
an intervention that includes the provision of in-hand medications is noteworthy given that considerable treatment 
access and cost barriers may pose an obstacle to tobacco treatment. In 2014, the Affordable Care Act extended 
cessation coverage benefits [87], yet many patients remain unable to obtain, and receive coverage for, smoking 
cessation medications.  If our IC treatment is effective, we will explore the relative contribution of the counseling 
and medication components; we intentionally did not select a factorial design, which would have allowed us to 
assess the independent effects of the counseling and medication, as previous work supported the use of 
combined treatment as the strongest intervention.  
There are many design innovations of this work that will facilitate its implementation. Firstly is our ability to 
overcome system, provider, and patient barriers to intervene with smokers during the critical time period of cancer 
diagnosis. Correspondingly, our collaborative care approach links tobacco and oncology providers in a way that is 
sustainable and minimizes oncology provider burden. In the spirit of integration, our flexible inclusion criteria and 
telehealth counseling delivery modality maximizes patient inclusivity and accessibility; specifically, treating 
patients regardless of their level of quit motivation, cancer stage, or smoking cessation medication uptake. Our 
evidence-based treatment, guided by behavior change models that address the interplay of emotions and 
cognitions, is continued throughout the patients’ cancer diagnosis, treatment determinations, and course; it is 
flexible in that it accommodates real world cancer treatment schedules among patients with a variety of tobacco-
related and non-tobacco-related cancers. 
At trial conclusion, we will investigate several unanswered questions about the provision of tobacco 
treatment as part of comprehensive cancer care. Specifically, we will assess why and how the proposed tobacco 
treatments work, for whom, and which patients may be reached. These answers will ensure the maximal impact 
of the disseminated results. To inform future implementation efforts for uptake of this treatment for cancer centers, 
we will assess the cost of each treatment. This information will help guide future research on the long-term impact 
of tobacco treatment on cancer care outcomes.   
 
 
 
 
 
 

25 
 
Declarations 
Abbreviations 
AACR: American Association for Cancer Research; ASCO: American Society for Clinical Oncology; BCC: 
Behavioral Change Consortium; CanCORS: Cancer Care Outcomes Research and Surveillance; CO: Air carbon 
monoxide; ECOG: Eastern Cooperative Oncology Group; EHR: Electronic health record; EQ-5D-5L: EuroQol 5-
Dimensional 5-Level Quality of Life survey; FDA: Food and Drug Administration; GAD-7: Generalized Anxiety 
Disorder-7; GEE: Generalized Estimating Equations; GI: Gastrointestinal; GU: Genito-urinary; HBM: Health Belief 
Model; HCAHPS: Hospital Consumer Assessment of Healthcare Providers and Systems;  IC: Intensive 
Counseling; MGH: Massachusetts General Hospital; MI: Motivational interviewing; MOS: Medical Outcomes 
Study; MSKCC: Memorial Sloan Kettering Cancer Center; NCCN: National Comprehensive Cancer Network; NCI: 
National Cancer Institute; NIH: National Institutes of Health; NRT: Nicotine replacement therapy; PHS: Public 
Health Service; PHQ-9: Patient Health Questionnaire-9; PI: Principal investigator; PIQ: Partner Interaction 
Questionnaire; PSS-4: Perceived Stress Scale-4; QOPI: Quality Oncology Practice Initiative; RA: Research 
Assistant; REDCap: Research Electronic Data Capture; SC: Standard of Care; SHSe: Second hand smoke 
exposure; SRM: Self-Regulation Model; SR: [Buproprion] sustained release; TTS: Tobacco treatment specialist; 
TTP: Tobacco treatment program 
 
Ethics approval and consent to participate 
The study is approved by the MGH/Partners Health System Institutional Review Board and the Memorial Sloan 
Kettering Cancer Center Institutional Review Board. Informed consent was obtained from all participants prior to 
participation in study activities. 
Consent for publication 
Not applicable.  
 
Availability of data and material 
Data requests can be directed to the corresponding author. 
 
Conflicts of interest 
Dr. Nancy Rigotti has a research grant and has been a consultant (without honorarium) for Pfizer.  Drs. Rigotti 

26 
 
and Park receive royalties from UpToDate 
. 
Author’s contributions 
All authors contributed to the design of the study. EP, JO, GP, SB, KH and EF contributed to the drafting of the 
manuscript.  All authors read and approved of the final manuscript. 
Funding 
This work was supported by the National Cancer Institute (5 R01 CA166147-05). The NIH/NCI had no role in the 
design, data collection or analysis, writing of this article, or decision to submit the article for publication. The 
content is solely the responsibility of the authors and does not necessarily represent the official views of the 
National Institutes of Health. 
 
Trial Registration 
 Integrating Tobacco Treatment into Cancer Care: A Randomized Controlled Comparative Effectiveness Trial (# 
NCT01871506). Registered June 4, 2013. 
 
Acknowledgements 
The authors would like to acknowledge the work of the cancer center oncologists and medical staff who assisted 
with the study. In particular, they would like to thank the following individuals for their guidance and support in 
carrying out the goals of this project: William F. Pirl, MD, Jennifer Temel, MD, Mary Ellen Wewers, RN, PhD, 
MPH, Robert A Schnoll, PhD, Carolyn Dresler, MD, MPA, and Adam O. Goldstein, MD, MPH. Additionally, the 
authors would like to thank Pfizer for their generous contribution of varenicline for trial participant use. 
Authors’ information 
Dr. Park is an Associate Professor of Psychiatry at Massachusetts General Hospital/Harvard Medical School and 
a Senior Scientist in the Mongan Institute for Health Policy. She is Associate Director of the MGH Cancer Center 
Survivorship Program and has leadership roles in the MGH Tobacco Research & Treatment Center and the MGH 
Benson-Henry Institute for Mind Body Medicine.  
Dr. Jamie Ostroff is Chief of the Behavioral Sciences Service and Director of the Tobacco Treatment Program in 
the Department of Psychiatry and Behavioral Sciences at the Memorial Sloan Kettering Cancer Center.  

27 
 
References 
[1.] American Cancer Society: Cancer Facts & Figures 2011. http://www.cancer.org/acs/groups/content/ 
@epidemiologysurveilance/documents/document/acspc-029771.pdf; 2011. Accessed 26 Feb 2016.  
[2.] U.S. Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of 
Progress: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, 
Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health 
Promotion, Office on Smoking and Health, 2014.  
[3.]  American Cancer Society: Cancer Facts & Figures 2015. 
http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf. Accessed 26 Feb 
2016.        
[4.] Garces YI, Schroeder DR, Nirelli LM, Croghan GA, Croghan IT, Foote RL, et al. Second primary tumors 
following tobacco dependence treatments among head and neck cancer patients. Am J Clin Oncol. 2007; 
30(5):531-539. 
 
[5.] Richardson GE, Tucker MA, Venzon DJ, Linnoila RI, Phelps R, Phares JC, et al. Smoking cessation after 
successful treatment of small-cell lung cancer is associated with fewer smoking-related second primary cancers. 
Ann Intern Med. 1993; 119(5):383-390. 
[6.] Tucker MA, Murray N, Shaw EG, Ettinger DS, Mabry M, Huber MH, et al. Second primary cancers related to 
smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre. J Natl Cancer Inst. 1997; 
89(23):1782-1788. 
[7.] Joshu CE, Mondul AM, Meinhold CL, Humphreys EB, Han M, Walsh PC, et al. Cigarette smoking and 
prostate cancer recurrence after prostatectomy. J Natl Cancer Inst. 2011; 103(10):835-838. 
[8.] Fleshner N, Garland J, Moadel A, Herr H, Ostroff J, Trambert R, et al. Influence of smoking status on the 
disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma of the 
bladder. Cancer. 1999; 86(11):2337-2345. 
[9.] Rice D, Kim HW, Sabichi A, Lippman S, Lee JJ, Williams B, Vet al. The risk of second primary tumors after 
resection of stage I nonsmall cell lung cancer. Ann Thorac Surg. 2003; 76(4):1001-1007. 
[10.] Do KA, Johnson MM, Doherty DA, Lee JJ, Wu XF, Dong Q, et al. Second primary tumors in patients with 
upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States). Cancer Causes Control. 
2003; 14(2):131-138. 
[11.] Garces YI, Yang P, Parkinson J, Zhao X, Wampfler JA, Ebbert JO, et al. The relationship between cigarette 
smoking and quality of life after lung cancer diagnosis. Chest. 2004; 126(6):1733-1741 
[12.] Gritz ER, Fingeret MC, Vidrine DJ, Lazev AB, Mehta NV, Reece GP. Successes and failures of the 
teachable moment: smoking cessation in cancer patients. Cancer. 2006; 106(1):17-27. 
[13.] Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung 
cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010; 340:b5569. 
[14.] Westmaas JL, Newton CC, Stevens VL, Flanders WD, Gapstur SM, Jacobs EJ. Does a recent cancer 
diagnosis predict smoking cessation? An analysis from a large prospective US cohort. J Clin Oncol. 2015; 33(15): 
1647-52. 

28 
 
[15.]  Daniel M, Keefe FJ, Lyna P, Peterson B, Garst J, Kelley M, et al. Persistent smoking after a diagnosis of 
lung cancer is associated with higher reported pain levels. J Pain. 2009; 10(3):323-328. 
[16.]  Danson SJ, Rowland C, Rowe R, Ellis S, Crabtree C, Horsman JM, et al. The relationship between smoking 
and quality of life in advanced lung cancer patients: a prospective longitudinal study. Support Care in Cancer. 
2015; 24:4. 
[17.] Dresler CM. Is it more important to quit smoking than which chemotherapy is used? Lung Cancer. 2003; 
39(2):119-124. 
[18.] Shen T, Le W, Yee A, Kamdar O, Hwang PH, Upadhyay D. Nicotine induces resistance to chemotherapy in 
nasal epithelial cancer. Am J Rhinol Allergy. 2010; 24(2):e73-77. 
[19.] Chen AM, Chen LM, Vaughan A, Sreeraman R, Farwell DG, Luu Q, et al. Tobacco smoking during radiation 
therapy for head-and-neck cancer is associated with unfavorable outcome. Int J Radiat Oncol Biol Phys. 2011; 
79(2):414-419. 
[20.] Kelemen LE, Warren GW, Koziak JM, Kobel M, Steed H. Smoking may modify the association between 
neoadjuvant chemotherapy and survival from ovarian cancer. Gynecol Oncol. 2016; 140(1):124-130. 
[21.] Jung KH, Kim SM, Choi MG, Lee JH, Noh JH, Sohn TS, et al. Preoperative smoking cessation can reduce 
postoperative complications in gastric cancer surgery. Gastric Cancer. 2015;18(4):683-690. 
[22.] Zhang J, Kamdar O, Le W, Rosen GD, Upadhyay D. Nicotine induces resistance to chemotherapy by 
modulating mitochondrial signaling in lung cancer. Am J Respir Cell Mol Biol. 2009; 40(2):135-146. 
[23.] Xu J, Huang H, Pan C, Zhang B, Liu X, Zhang L. Nicotine inhibits apoptosis induced by cisplatin in human 
oral cancer cells. Int J Oral Maxillofac Surg. 2007;36(8):739-744. 
[24.] Gritz ER. Rationale for Treating Tobacco Dependence in the Cancer Setting. Conference presentation at: 
Treating Tobacco Dependence at the National Cancer Institute’s Cancer Centers. 2009.  
[25.] Park ER, Japuntich s, Rigotti NA, Traeger L, He Y, Wallace R, et al. A snapshot of smokers following lung 
and colorectal cancer diagnosis. Cancer. 2012; 118(12):3153-64. 
[26.] Bellizzi KM, Rowland JH, Jeffrey DD, McNeel T. Health behaviors of cancer survivors: examining 
opportunities for cancer control intervention. J Clin Oncol. 2005; 23(34):8884-93. 
[27.] Tseng T, Lin H, Martin MY, Chen T, Partridge EE. Disparities in smoking and cessation status among cancer 
survivors and non-cancer individuals: A population based study from the National Health and Nutrition 
Examination Survey. J Cancer Surviv. 2010; 4(4): 313-21. 
[28.] Bryant J, Boyes AW, Hall A, Girgis A, D’Este C, Sitas F. Prevalence and factors related to smoking and 
smoking cessation 6 months following a cancer diagnosis: a population-based study. J Cancer Surviv. 2016. 
[29.] Westmaas JL, Alcaraz KI, Berg CJ, Stein KD. Prevalence and correlates of smoking and cessation-related 
behavior among survivors of ten cancers: findings from a nationwide survey nine years after diagnosis. Cancer 
Epidemiol Biomarkers Prev. 2014; 23(9):1783-1792. 
[30.] The Joint Commission: Tobacco and Alcohol Measures. 
http://www.jointcommission.org/tobacco_and_alcohol_measures/. Accessed 26 Feb 2016. 

29 
 
[31.] American Recovery and Reinvestment Act of 2009: Senate Reports, Vol 155 (2009). 
https://www.biomedcentral.com/submissions/preparing-your-manuscript-and-supporting-information. Accessed 2 
March 2016 
[32.] Blumenthal D, Tavenner M. The “Meaningful Use” Regulation for Electronic Health Records. N Engl J Med. 
2010; 363: 501-04. 
[33.] Simmons VN, Litvin EB, Patel RD, Jacobson PB, McCaffrey JC, Bepler G, et al. Patient-provider 
communication and perspectives on smoking cessation and relapse in the oncology setting. Patient Educ Couns. 
2009; 77(3): 398-403. 
[34.] Burke L, Miller LA, Saad A, Abraham J. Smoking behaviors among cancer survivors: An observational 
clinical study. 2009; 5(1): 6-9. 
[35.] Bjurlin MA, Goble SM, Hollowell CM. Smoking cessation assistance for patients with bladder cancer; a 
national survey of American urologists. J Urol. 2010; 184(5): 1901-06. 
[36.] American Society of Clinical Oncology. Tobacco Cessation and Quality Cancer Care. Journal of Oncology 
Practice. 2009; 5(1): 2-5. 
[37.] Gritz ER, Nisenbaum R, Elashoff RE, Holmes EC. Smoking behavior following diagnosis in patients with 
Stage I non-small-cell lung cancer. Cancer Causes Control. 1991; 2: 105-12. 
[38.] Dresler CM, Bailey M, Roper CR, Patterson GA, Cooper JD. Smoking cessation and lung cancer resection. 
Chest. 1996; 110(5): 1199-202. 
[39.] Sarna L. Smoking behaviors of women after diagnosis with lung cancer. J Nurse Scholarship. 1995; 27(1); 
34-5. 
[40.] Cooley ME, Emmons KM, Haddad R, Wang Q, Posner M, Bueno R, et al. Patient reported receipt of and 
interest in smoking-cessation interventions after a diagnosis of cancer. Cancer. 2011;117(13):2961-9 
[41.] Farley A, Aveyard P, Kerr A, Naidu B, Dowswell G. Surgical lung cancer patients’ views about smoking and 
support to quit after diagnosis: a qualitative study. J Cancer Surviv. 2015: 1-8. 
[42.] Patsakham KM, Ripley-Moffitt C, Goldstein AO. Tobacco use and dependence treatment: a clinical 
compnent of cancer care. Clin J Oncol Nurs. 2009; 13(5): 463-64. 
[43.] Villanti AC, Bover Manderski MT, Gundersen DA, Steinberg MB, Delnevo CD. Reasons to quit and barriers 
to quitting smoking in US young adults. Fam Pract. 2016. 
[44.] Robinson WR, Regn R, Shamsnia L. The effect of a smoking cessation program on women with gynecologic 
cancer. Gynecol Oncol. 2015; 139(1):182. 
[45.] Morgan G, Schnoll R, Alfano C, Evans S, Goldstein A, Ostroff J, et al. National Cancer Institute Conference 
on Treating Tobacco Dependence at Cancer Centers. J Oncol Pract. 2011; 7(3): 178-182. 
[46.] Fiore MC, Jaen CR, Baker TB, et al. Treating tobacco use and dependence: 2008 update. Rockville, MD: 
U.S. Department of Health and Human Services. Public Health Service. 2008. 
 

30 
 
[47.] Ostroff JS, Burkhalter JE, Cinciripini PM, Li Y, Shiyko MP, Lam CY, et al. Randomized trial of a pre-surgical 
scheduled reduced smoking intervention for patients newly diagnosed with cancer, Health Psychol. 2014; 
33(7):737-4.  
[48.] De Moor JS, Elder K, Emmons KM. Smoking prevention and cessation interventions for cancer survivors. 
Semin Oncol Nurs. 2008; 24(3): 180-192. 
[49.] Cox LS, Patten CA, Ebbert JO, Drews AA, Croghan GA, Clark MM, et al. Tobacco Use Outcomes Among 
Patients with Lung Cancer Treated for Nicotine Dependence. J Clin Oncol. 2002; 20(16): 3461-9. 
[50.] Schnoll RA, Zhang B, Rue M, Krook JE, Spears WT, Marcus AC, et al. Brief physician-initiated quit-smoking 
strategies for clinical oncology settings: a trail coordinated by the Eastern Cooperative Oncology Group. J Clin 
Oncol. 2003; 21(2): 355-65. 
[51.] Leventhal EA, Crouch M. Are there differences in perceptions of illness across the lifespan? In: Petrie KJ, 
Weinman JA, editors. Perceptions of health and illness: Current research and applications. Netherlands: Harwood 
Academic Publishers; 1997. p. 77-102. 
[52.] Leventhal H, Nerenz D, Strauss A. Self-regulation and the mechanisms for symptom appraisal. In: Mechanic 
D, editor. Monograph series in psychosocial epidemiology 3: Symptoms, illness behaviour and help-seeking. New 
York: Neale Watson; 1982. p. 55-86. 
[53.] Becker MH. The Health Belief Model and Personal Health Behavior. Health Education Monographs.1974; 2: 
324-508. 
[54.] Miller W, Rollnick S. Motivational interviewing. New York: The Guilford Press; 1991. 
[55.] Bellg AJ, Borrelli B, Resnick B, Hecht J, Minicucci DS, Ory M, et al. Enhancing treatment fidelity in health 
behavior change studies: best practices and recommendations from the NIH Behavior Change Consortium. 
Health Psychol. 2004; 23(5):443-51. 
[56.] Moyers TB, Martin T, Manuel JK, Miller WR, Ernst D. Motivational interviewing treatment integrity (MITI 
3.1.1): Revised global scales. 2010. http://casaa.unm.edu/download/MITI3_1.pdf. Accessed 2 March 2016 
[57.] Moyers TB, Miller WR, Hendrickson SM. How does motivational interviewing work? Therapist interpersonal 
skill predicts client involvement within motivational interviewing sessions. J Consult Clin Psychol. 2005; 73(4): 
590-8.  
[58.] Catley D, Harris KJ, Mayo MS, Hall S, Okuyemi KS, Boardman T, et al. Adherence to principles of 
motivational interviewing and client within-session behavior. Behav Cogn Psychother. 2006; 34: 43-56. 
[59.] Heatherton TF, Kozlowski LT, Frecker RC, Rickert W, Robinson J. Measuring the heaviness of smoking: 
using self-reported time to the first cigarette of the day and number of cigarettes smoked per day. Br J Addict. 
1989; 84(7):791-9. 
[60.]  Holland JC, Anderson B, Breitbart WS, et al. The NCCCN Distress Management Guidelines, version 1, 
2007. Available at: www.nccn.org/professsionals/physician_gls/PDF/distress.pdf. Accessed September 21, 2006.   
[61.]   Piriz IE, Ferro NE, Di Pretoro M, Cesarco R, Hannois A, Cuello GN, et al. Distress in oncology patients: 
Distress thermometer in a Latin American study. J Clin Oncol. 2005; 23(June 1 Supplement): 8211. 
[62.] Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the 
GAD-7. Arch Intern Med. 2006; 166(10):1092-7. 

31 
 
[63.] Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity measure. J Gen 
Intern Med. 2001; 16(9):606-613. 
[64.] Levenstein S, Prantera C, Varvo V, Scribano ML, Berto E, Luzi C, et al. Development of the Perceived 
Stress Questionnaire: a new tool for psychosomatic research. J Psychosom Res. 1993; 37(1):19-32. 
[65.] Fife BL, Wright ER. The dimensionality of stigma: a comparison of its impact on the self of persons with 
HIV/AIDS and cancer. J Health Soc Behav. 2000; 41(1): 50-67. 
[66.] Biener L, Abrams DB. The contemplation ladder: validation of a measure of readiness to consider smoking 
cessation. Health Psychol. 1991; 10(5): 360-5. 
[67.] Park ER, Ostroff JS, Rakowski W, Gareen IF, Diefenbach MA, Fiebelmann S, et al. Risk perceptions among 
participants undergoing lung cancer screening: baseline results from the National Lung Screening Trial. Ann 
Behav Med. 2009; 37: 268-279. 
[68.] Condiotte, MM, Lichtenstein E. Self-efficacy and relapse in smoking cessation programs. J Consult Clin 
Psychol. 1981; 49: 648-58. 
[69.] Daniel M, Keefe FJ, Lyna P, Peterson B, Garst J, Kelley M, et al. Persistent smoking after a diagnosis of 
lung cancer is associated with higher reported pain levels. J Pain. 2009; 10(3):323-8. 
[70.] Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new 
instrument for psychiatric practice and research. Psychiatry Res. 1989; 28(2):193-213. 
[71.] West R, Hajek P. Evaluation of the mood and physical symptoms scale (MPSS) to assess cigarette 
withdrawal. Psychopharmacology (Berl). 2004. 177(1-2):195-9. 
[72.] The Social Science Research Center: The National Social Climate of Tobacco Control, 2008. 
http://www.socialclimate.org/pdf/us_scs_08_Report.pdf. Accessed 26 Feb 2016.   
[73.] Cohen S, Lichtenstein E. Partner behaviors that support quitting smoking. J Consult Clin Psychol. 1990; 
58(3):304-9. 
[74.] Sherbourne CD, Stewart AL. The MOS social support survey. Soc Sci Med. 1991; 32(6): 705-14. 
[75.] Ayanian J, Zaslavsky A, Arora N, Kahn K, Malin J, Ganz P et al. Patients’ experiences with care for lung 
cancer and colorectal cancer: findings from the cancer care outcomes research and surveillance consortium. J 
Clin Onocol. 2010; 28(27):4154-4161. 
[76.] Fiore MC, Jaen CR, Baker TB, Bailey WC, Benowitz NL, Curry SJ et al. Treating tobacco use and 
dependence: 2008 update. Clinical practice guideline. U.S. Department of Health and Human Services. Public 
Health Service. 2008. 
[77.] Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of 
the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011; 20(10):1727-36. 
[78.] Martinez ME, Reid M, Jiang R, Einspahr J, Alberts DS. Accuracy of self-reported smoking status among 
participants in a chemoprevention trial. Prev Med. 2004; 38(4):492-497. 
[79.] Knudsen N, Schulman S, van den Hoek J, Fowler R. Insights on how to quit smoking: a survey of patients 
with lung cancer. Cancer Nurs. 1985; 8(3): 145-150.  

32 
 
[80.] Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer 
Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the 
TNM Classification of malignant tumours. J Thorac Oncol. 2007; 2(8): 706-14. 
[81.] Rigotti N, Clair C, Munafo MR, Stead LF. Interventions for smoking cessation in hospitalised patients. 
Cochrane Database Syst Rev. 2012; 5: CD001837. 
[82.] Hayden D, Pauler DK, Schoenfeld D. An estimator for treatment comparisons among survivors in 
randomized trials. Biometrics. 2005; 61(1): 305-310.  
[83.] Rubin DB. Multiple imputation for nonresponse in surveys. New York: John Wiley & Sons, Inc.; 1987. 
[84.] Baron RM, Kenny DA. The moderator-mediator variable distinction in social psychological research: 
conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986; 51(6): 1173-1182.  
[85.] Mackinnon DP, Fairchild AJ. Current Directions in Mediation Analysis. Curr Dir Psychol Sci. 2009; 18(1): 16.  
[86.] Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, et al. Efficacy of varenicline, an 
alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release buproprion for 
smoking cessation: a randomized controlled trial. JAMA. 2006; 296(1):56-63. 
[87.] FAQs about affordable care act implementation (part XIX): United States Department of Labor. 
http://www.dol.gov/ebsa/faqs/faq-aca19.html (2014). Accessed 2 March 2016.