Smoking Cessation Interventions and Cessation Rates in the Oncology Population

Abstract

Objectives

To evaluate tobacco smoking cessation interventions and cessation rates in the oncology population through a systematic review and meta-analysis.

Data Sources

The literature was searched using PubMed, Google Scholar, Medline, EMBASE, and the Cochrane Library (inception to October 2012) by 3 independent review authors.

Review Methods

Studies were included if they were randomized controlled trials (RCTs) or prospective cohort (PCs) studies evaluating tobacco smoking cessation interventions with patients assigned to a usual care or an intervention group. The primary outcome measure was smoking cessation rates. Two authors extracted data independently for each study. When applicable, disagreements were resolved by consensus.

Results

The systematic review identified 10 RCTs and 3 PCs. Statistical analysis was conducted using StatsDirect software (Cheshire, UK). Pooled odds ratios (ORs) for smoking cessation interventions were calculated in 2 groups based on follow-up duration. The therapeutic interventions included counseling, nicotine replacement therapy, buproprion, and varenicline. Smoking cessation interventions had a pooled odds ratio of 1.54 (95% confidence interval [CI], 0.909-2.64) for patients in the shorter follow-up group and 1.31 (95% CI, 0.931-1.84) in the longer follow-up group. Smoking cessation interventions in the perioperative period had a pooled odds ratio of 2.31 (95% CI, 1.32-4.07).

Conclusion

Our systematic review and meta-analysis demonstrate that tobacco cessation interventions in the oncology population, in both the short-term and long-term follow-up groups, do not significantly affect cessation rates. The perioperative period, though, may represent an important teachable moment with regard to smoking cessation.

Keywords

tobacco smoking cessation cancer oncology

Cigarette smoking and alcohol consumption synergistically increase the risk of developing squamous cell carcinoma of the head and neck.^1,2 Tobacco carcinogens also further advance the molecular progression of squamous cell carcinomas of the head and neck.^1,2 Cigarette smoking has been related to approximately 90% of diagnoses of lung cancer in countries with a high prevalence of smoking. Furthermore, the increased incidence of lung cancer from smoking is proportional to the length and intensity of smoking history.³ Smoking cessation is particularly important for patients who have smoking-related cancers, such as head and neck or lung cancer.^3,4

Persistent tobacco smoking in the oncology population has a multitude of adverse effects during the treatment of the malignancy, increases the risk of a recurrence or a second primary tumor, and reduces survival.^5,6 These risks are particularly apparent in patients with head and neck or lung cancer. Cigarette smoking also increases the perioperative risks of general anesthesia, poor wound healing, and cardiovascular events.^7-9

Radiotherapy is also less effective in patients with head and neck cancer who smoke. Patients with head and neck cancer who smoke tobacco have a lower rate of complete response and poorer 2-year survival rate than nonsmokers and those who quit prior to treatment.¹⁰ Radiotherapy-induced complications such as mucositis, dry mouth, loss of taste, voice problems, impaired pulmonary function and wound healing, and prolonged tissue and bone necrosis are exacerbated by smoking.^5,11 Despite these adverse health effects, 23% to 35% of patients with head and neck cancer and 13% to 20% of patients with lung cancer who smoked prior to diagnosis continue to do so after diagnosis.^5,6,12-14 Comorbid conditions such as depression, disease-related anxiety, and alcohol abuse often make cessation challenging.

The health care setting is an ideal place to initiate cessation interventions with smokers who are newly diagnosed with a malignancy.¹⁵ The diagnosis of cancer allows an opportunity for health care professionals to review lifestyle habits with patients.^16,17 Gritz et al⁴ emphasize the importance of this opportunity as “the teachable moment.” However, studies in the literature continue to demonstrate that 50% of surgeons do not routinely discuss smoking cessation interventions with patients despite the benefits.^9,18

A summary report of smoking cessation interventions in the health care setting was first described by Schwartz.¹⁹ Interventions may be hospital based, community based, or based on individual counseling. Current smoking cessation interventions can be pharmacological, nonpharmacological, or a combination of both.²⁰ Examples of effective approaches include the 5 As (ask, assess, advise, assist, arrange), identifying tobacco use in patients, motivating them to quit, and supporting them to quit through brochures or pamphlets, counseling, and pharmacotherapy.^1,20,21 Regular follow-up is also a critical component of cessation interventions.^1,20

Pharmacotherapy for smoking cessation includes nicotine replacement therapy (NRT), bupropion (norepinephrine-dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist), and varenicline (nicotine receptor partial agonist). Noninvasive biochemical markers to verify smoking cessation are urine cotinine, saliva cotinine, and breath carbon monoxide (CO).

Tobacco cessation has substantial benefits in the oncology population. We previously conducted a systematic review and meta-analysis on randomized controlled trials (RCTs) of smoking cessation interventions in the cancer population²²; however, the benefits of smoking cessation interventions were not statistically significant. As there have been more studies in the literature since the previous review, the primary aim was to update, reevaluate, and systematically review the literature to summarize tobacco cessation interventions and the associated smoking cessation quit rates in the oncology population.

Methods

This systematic review and meta-analysis was performed in accordance with a predetermined protocol consisting of eligibility criteria, a search strategy, outcomes, and statistical analysis. The review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of 2009.²³ Our primary aim was to perform a pooled analysis of smoking cessation rates if appropriate.

Literature Search Strategy

The literature was searched using PubMed, OVID Medline (1950 through October 2012), EMBASE (1980 through October 2012), Google Scholar, and the Cochrane Library (Cochrane Database of Systematic Reviews [2012, Issue 10]). Similar strategies were applied to search all the databases. Relevant articles and abstracts were selected and reviewed, and the reference lists from these sources and recent review articles or meta-analyses were searched for additional publications.

The literature search of the electronic databases combined disease-specific keywords (cancer, neoplasm, and malignancy) with outcome-specific keywords (tobacco cessation, smoking cessation, nicotine cessation, quit rates, patient education, and patient intervention). The literature search was not limited to study design or publication date to ensure all relevant published articles were captured. Three study authors (S.N., M.K.G., and D.D.S.) performed a search using individual strategies.

Study Selection Criteria

The 3 authors reviewed the studies identified by the search strategies for relevance. Disagreements were resolved by consensus. Reasons for exclusion were noted. Articles were included in the systematic review of the evidence if they were fully published reports or abstracts of RCTs or prospective cohort (PC) studies evaluating a tobacco smoking cessation intervention vs standard usual care in the adult smoking cancer population (>18 years of age). To be included, trials had to report cessation rates and follow-up.

Articles were excluded if they were published in a language other than English, did not discuss a tobacco cessation intervention, did not report cessation rates at follow-up, discussed nontobacco products without separation of data, or were in the pediatric population.

Data Extraction

Relevant data were extracted from fully published reports by 2 independent review authors (S.N. and M.K.G.) using prescribed tables. Any disagreement was resolved through discussion and consensus. Primary authors of included studies were contacted if further elaboration on data was needed.^4,15 Where studies were duplicated, the larger data set was used for the analysis.¹⁵

Statistical Analysis

Statistical calculations were performed using the StatsDirect software (Cheshire, UK). Prospectively gathered data from the RCTs and PC studies were evaluated to calculate a pooled odds ratio (OR). The OR was a ratio of the odds of tobacco cessation in the intervention group vs the odds of tobacco cessation in the control group. The ORs were calculated where data were available by intention-to-treat analysis.

The random-effects model of pooled OR was calculated using the DerSimonian-Laird method.^24,25 The decision to use either a random-effects model or a fixed-effects model was based on calculation of heterogeneity of the data using an I² calculation. Where heterogeneity of the data was large, a random-effects model was used. Confidence intervals of the pooled ORs were calculated using the Greenland-Robins variance formula.²⁶

Results

Literature Search

Two thousand thirty studies were identified through the literature review with 52 retrieved for consensus and 39 studies^27-65 excluded on further review. Ten RCTs^{5,15,16,66-72} and 3 PC studies^21,73,74 met the inclusion criteria ( Figure 1 ).

Figure 1.

Flow diagram outlining our search strategy.

Trial Characteristics

Published studies ( Table 1 ) were single-center^{15,16,21,66,68-70,72,73} or multicenter.^4,5,67 There were a total of 1301 patients. The included studies did not show significant differences in baseline characteristics of mean age and sex distribution except in studies that included only patients with head and neck cancer ( Table 1 ).^15,16,74 Smoking cessation interventions were delivered by the health care team. Interventions were nonpharmacological (cognitive-behavioral therapy, self-help material, education modules, motivational interviewing) or pharmacological (nicotine replacement therapy,^{5,16,67,69,70,72} bupropion,^21,67,70 or varenicline^21,74) ( Table 2 ). All studies evaluated tobacco smoking.

Table 1.

Trial characteristics.

Author, Year	Study Dates	No. of Patients	Current Smokers	Age, y, Mean ± SD (Range)	Sex, M/F, No.	Mean Follow-up, wk	Primary Site of Malignancy, No. (%) of Patients
Randomized controlled trials
Multicenter
Gritz et al, 1993⁴	NR	186	96	C: 57.8 ± 9.5	137/49	52	C: buccal cavity, 59 (52.7); pharynx, 6 (5.4), larynx, 47 (42.0)
				NC: 59.5 ± 9.5			NC: buccal cavity, 58.3 (42); pharynx, 5 (6.9); larynx, 25 (34.7)
Duffy et al, 2006⁶⁷	2000-2003	184	136	57 ± 9.9	155/29	24	Head and neck: larynx (33); oropharynx/hypopharynx (30); oral cavity/other (37)
Thomsen et al, 2010⁷²	NR	130	130	I: 57.5 (35-79)	0/100	1.5, 4, 12, 24, and 52	Breast (100)
				U: 56.5 (36-82)
Single center
Schnoll et al, 2003⁵	NR	74	108	57 ± 11.4	38/36	12	Lung (69); head and neck (31)
Schnoll et al, 2010⁷⁰	2002-2008	246	246	54.8 ± NR	128/118	24	Lung or head and neck (32.2); breast (21); prostate (15); lymphoma (9); colorectal (5); kidney, pancreas, liver (4); GU (3); esophageal (3); other or multiple primaries (5)
Wakefield et al, 2004¹⁶	1999-2001	137	135	I: 52.6 ± 13.8	85/52	24	Lung (12); head and neck (17); bladder (2); breast (13); prostate (9); colorectal (10); leukemia (10); lymphoma (15); testicle (4); other (8)
				U: 51.9 ± 11.5
Wewers et al, 1994¹⁵	NR	30	30	I: 56.4 ± 13.6	10/20	5	Head and neck (83.3); breast cancer (6.7); prostate cancer (6.7); cervical cancer (3.3)
				U: 53.2 ± 13.3
Griebel et al, 1998⁶⁸	NR	28	28	I: 50.2 ± 12.4	14/16	6	Gynecologic (6.21); breast (5.18), gastrointestinal (4.14); thoracic (4.14); urologic (4.14); neurologic (4.14); head and neck (2.7)
				U: 51.9
				I: 50.2 ± 10.5
Schnoll et al, 2005⁶⁹	NR	109	108	I: 58.7 ± 9	59/50	4 and 12	Head and neck (69); lung (31)
				U: 57.7 ± 10.1
Stanislaw and Wewers, 1994⁶⁶	NR	26	26	I: 58.25 ± 13.82	7/19	5	Head and neck (81); breast (7.7); prostate (7.7); uterine cervix (3.8)
				U: 53.43 ± 14.12
Prospective cohort studies
Park et al, 2011²¹	January 2008 to August 2009	17; 32	74	57.7 (12.4)	13/29	2 and 12	Thoracic (100)
Gosselin et al, 2011⁷⁴	May-August 2007	6052	112		49/63	4	Head and neck (100)
Browning et al, 2000⁷³	NR	25	25	NR	NR/NR	24	Lung (100)

Abbreviations: C, completers of 12 month follow-up; GU, genitourinary; I, intervention; NC, completers of 12 month follow-up; NR, not reported; U, usual care.

Table 2.

Tobacco smoking cessation intervention characteristics.

Author, Year	Cigarettes Smoked/d, Mean ± SD	Usual Care (No. of Patients)	Intervention (No. of Patients)	Setting	Nonpharmacological	Pharmacological	Confirmation of Smoking Cessation
Randomized controlled trials
Multicenter
Gritz et al, 1993⁴	C: 24.0 ± 12.4	46	50	Clinic	Counseling, booklets	None	Self-report, UC levels^a
	NC: 21.4 ± 11.3
Duffy et al, 2006⁶⁷	NR	91	93		Cognitive-behavioral therapy	Nicotine replacement therapy and buproprion	Self-report
Thomsen et al, 2010⁷²	NR/I: 31.5 (8.8-64.5) (pack years)	62	58	Perioperative	Counseling	Nicotine replacement therapy	Self-reported and BCO
	C: 27 (3.8-81) (pack years)
Single center
Schnoll et al, 2003⁵	NR	218	217		Counseling	Nicotine replacement therapy	Self-report
Schnoll et al, 2010⁷⁰	I: 19.2 ± 12.3	57	52		Counseling	Nicotine replacement therapy	Self-reported
	U: 17.5 ± 11.2
Wakefield et al, 2004¹⁶	I: 21.7 ± 12.1	63	74		Motivational interviewing, smoking cessation booklets, family advice to quit	Nicotine replacement therapy	Self-report, BCO and UC levels
	U: 21.4 ± 10.9
Wewers et al, 1994¹⁵	I: 19.1 ± 7.7	16	14	Postoperative, in-hospital	Counseling, cessation booklets	None	Self-report and SC levels^b,c
	U: 23.4 ± 9.6
Griebel et al, 1998⁶⁸	I: 24.7 ± 14.5	18	18	Preoperative, in-hospital	Counseling, booklets	None	Self-report and SC^d
	U: 27.0 ± 19.8
Schnoll et al, 2005⁶⁹	I: 19.2 ± 12.3	57	52		Counseling	Nicotine replacement therapy	Self-reported
	U: 17.5 ± 11.2
Stanislaw and Wewers, 1994⁶⁶	I: 17.67 ± 5.19	14	12	Postoperative	Counseling	None	Self-reported and SC
	U: 21.78 ± 10.79
Prospective cohort studies
Park et al, 2011²¹	NR	17	32	Clinic	Counseling	Varenicline or buproprion	Self-reported and SC
Gosselin et al, 2011⁷⁴	NR	60	52	Clinic	Counseling	Varenicline	Self-reported
Browning et al, 2000⁷³	NR	11	14	Perioperative	Counseling	None	Self-reported and BCO

Abbreviations: BCO, breath carbon monoxide; I, intervention; NC, non-completers of 12 month follow-up; NR, not reported; SC, saliva cotinine; U, usual care; UC, urine cotinine.

Urine cotinine level of ≤50 ng/mL.

Saliva cotinine level of ≤10.0 ng/mL.

One patient declined SC level.

Saliva cotinine level of ≤14.0 ng/mL.

Tobacco Cessation Rates and Follow-up

All studies used self-reported rates of tobacco cessation. In addition, some studies used biochemical verification as well for smoking cessation. Four studies used breath testing of carbon monoxide (CO),^16,70,72,73 2 studies used urine cotinine levels,^4,16 and 4 studies used saliva cotinine levels^15,21,66,68 where possible to confirm self-reported rates ( Table 2 ). For those studies that had biochemical verification, self-reported rates were validated. Of 229 patients who reported quitting smoking, 215 were confirmed to have quit smoking biochemically (93.9%) ( Table 3 ).

Table 3.

Biochemical validation with breath carbon monoxide (BCO), urine cotinine (UC), or saliva cotinine (SC) of self-reported smoking cessation rates.

Author	Verification Method	Reported Nonsmokers	Total No. of Patients with Verification
Schnoll et al, 2010⁷⁰	BCO	44	44
Wakefield et al, 2004¹⁶	BCO and UC	21	9
Gritz et al, 1993⁴	UC	62	60
Wewers et al, 1994¹⁵	SC	17	17
Griebel et al, 1998⁶⁸	SC	5	5
Park et al, 2011²¹	SC	17	17
Thomsen et al, 2010⁷²	BCO	23	23
Stanislaw and Wewers, 1994⁶⁶	SC	15	15
Browning et al, 2000⁷³	BCO	25	25
Total		229	215

Cessation rates were reported at different follow-up times for the studies. Studies were evaluated in 2 groups based on follow-up duration. The group with the shorter follow-up period (n = 6) had a mean follow-up of 5 weeks,^{15,21,66,68-74} and the longer follow-up group (n = 7) was followed for at least 6 months.^4,5,16,67 In the second group, pooled rates were calculated from the 6-month abstinence rates in all studies except 1,⁴ which reported a 12-month rate ( Table 4 ).

Table 4.

Summary of tobacco smoking cessation rates.

	Intervention Group		Usual Care Group
Study	Total No. of Patients	No. (%) of Patients Who Ceased Smoking	Total No. of Patients	No. (%) of Patients Who Ceased Smoking
Long follow-up (mean 6 mo.)
Duffy et al, 2006⁶⁷	62	23	53	12
Schnoll et al, 2003⁵	215	30	214	25
Wakefield et al, 2004¹⁶	74	14	63	7
Gritz et al, 1993⁴	50	29	46	33
Schnoll et al, 2010⁷⁰	114	21	132	23
Park et al, 2011²¹	32	13	14	2
Thomsen et al, 2010⁷²	62	8	58	5
Browning et al, 2000⁷³	14	10	11	6
Short follow-up (<6 wk)
Wewers et al, 1994¹⁵	14	9	16	8
Griebel et al, 1998⁶⁸	18	3	18	2
Schnoll et al, 2005⁶⁹	52	22	57	26
Gosselin et al, 2011⁷⁴	52	7	60	8
Thomsen et al, 2010⁷²	62	17	58	6
Stanislaw and Wewers, 1994⁶⁶	12	9	14	6

For the purpose of pooling data, only self-reported data were pooled. The pooled OR was 1.54 (95% CI, 0.909-2.64; P = .108; I² = 8.7%) for patients in the shorter follow-up group ( Figure 2 ). The longer follow-up group had a pooled OR of 1.31 (95% CI, 0.931-1.84; P = .120; I² = 15.3%) ( Figure 3 ), which also indicated that the intervention was not statistically significant. The random-effects model was used to calculate both pooled ORs.

Figure 2.

Meta-analysis plot looking at odds ratios in the shorter follow-up group.^{15,66,68,69,72,74}

Figure 3.

Meta-analysis plot evaluating odds ratio through random effects for the longer follow-up group.^{4,5,16,21,67,70,72,73}

A sensitivity analysis was then performed evaluating various conditions. Comparing nonpharmacological therapy vs combination therapy, the pooled results were as follows: pooled OR of 1.35 (95% CI, 0.62-2.97; I² = 33.6%) and pooled OR of 1.40 (95% CI, 1.06-1.87; I² = 1.8%) ( Figures 4 and 5 ). The two primary settings in which smoking cessation interventions were offered were during the perioperative period or within the clinic. In the perioperative setting,^{15,66,68,72,73} the pooled OR was 2.31 (95% CI, 1.32-4.07; I² = 0%) ( Figure 6 ).

Figure 4.

Meta-analysis plot looking at odds ratios in the group with pure nonpharmacological intervention.^{4,15,66,68,73}

Figure 5.

Meta-analysis plot looking at odds ratios in the group with combination intervention (nonpharmacological + pharmacological intervention).^{5,16,21,67,69,72,74}

Figure 6.

Meta-analysis plot looking at odds ratios in the group with smoking cessation intervention during the perioperative period.^66,68,72,73

Finally, a subgroup analysis looking at studies with only self-reported tobacco cessation 15,66,68,72,73 (OR, 1.18; 95% CI, 0.86-1.64; I² = 0%) ( Figure 7 ) vs studies that had biochemical verification^{4,15,21,66,68,73} (OR, 1.62; 95% CI, 0.76-3.48; I² = 38.5%) ( Figure 8 ) showed a more favorable result for smoking cessation in patients who had biochemical verification of cessation.

Figure 7.

Meta-analysis plot looking at odds ratios in the group with self-reported rates of smoking cessation intervention.^{5,67,69,70,74}

Figure 8.

Meta-analysis plot looking at odds ratios in the group with biochemical verification of smoking cessation intervention.^{4,21,15,66,68,73}

Discussion

Although the primary aim of the systematic review and meta-analysis was achieved, a statistically significant difference was not demonstrated between cessation interventions and usual care in the oncology population, except in the perioperative period.

By including both PC studies and RCTs in the systematic review, we were able to identify 13 studies that met the inclusion criteria. The previous systematic review had identified 8 studies, which were all RCTs.²² We used a broad search strategy with multiple reviewers. When necessary, authors were contacted to provide additional data to ensure an accurate data set.^4,15 The identified studies were methodologically sound with prospectively gathered data, evaluating smoking cessation interventions in the oncology population with suitable control groups. The Cochrane Review Risk of Bias tool was applied to the RCTs, and all the studies were deemed to have a low risk of bias ( Table 5 ).⁷⁵ The risk of bias within the prospective cohort studies was not assessed, as the current instruments in the literature are limited to assess the risk of bias adequately.⁷⁵

Table 5.

Assessing risk of bias within randomized controlled trials.

Author, Year	Adequate Sequence Generation?	Allocation Concealment?	Blinding? (Patient-Reported Outcomes/Mortality)	Incomplete Outcome Data Addressed? (Short-Term Outcomes [2-6 wk])	Incomplete Outcome Data Addressed? (Longer-Term Outcomes [>6 wk])	Free of Selective Reporting?	Free of Other Bias?
Multicenter
Gritz et al, 1993⁴	Y	N	Y/Y	Y	Y	Y	Y
Duffy et al, 2006⁶⁷	Y	N	Y/Y	Y	Y	Y	Y
Thomsen et al, 2010⁷²	Y	N	Y/Y	Y	Y	Y	Y
Single center
Schnoll et al, 2003⁵	Y	N	Y/Y	Y	Y	Y	Y
Schnoll et al, 2010⁷⁰	Y	N	Y/Y	Y	Y	Y	Y
Wakefield et al, 2004¹⁶	Y	N	Y/Y	Y	Y	Y	Y
Wewers et al, 1994¹⁵	Y	N	N/Y	Y	Y	Y	Y
Griebel et al, 1998⁶⁸	y	N	N/Y	Y	Y	Y	Y
Schnoll et al, 2005⁶⁹	Y	N	Y/Y	Y	Y	Y	Y
Stanislaw and Wewers, 1994⁶⁶	Y	N	N/Y	Y	Y	Y	Y

Abbreviations: N, no; Y, yes.

All 13 studies had slightly different smoking cessation treatment plans. Only 1 study⁶⁹ looked at a purely pharmacological approach to tobacco cessation, whereas 5 studies had only a nonpharmacological approach.^{4,15,66,68,73} Five studies^{5,16,67,69,70} had a combination approach of nicotine replacement therapy, counseling, and/or cognitive-behavioral study. Duffy et al⁶⁷ evaluated the combination of cognitive-behavioral therapy in addition to bupropion and nicotine replacement therapy. The remaining 2 studies evaluated counseling with varenicline.^21,74 Since the previous systematic review, 3 of the most recent studies analyzed combination interventions, including both pharmacological and nonpharmacological therapy.^21,72,74

Like other systematic reviews and meta-analyses, the studies have some heterogeneity when comparing study design, treatment plans, and patient groups. Heterogeneity was also present with patient groups (perioperative or clinic-based enrollment), types of malignancies, and the length of follow-up. This type of heterogeneity is common and should be incorporated into systematic reviews.²⁵ The I² heterogeneity score, though, is fairly low at 6.6% (95% CI, 0%-50.9%). Both PC studies and RCTs were sought to broaden the number of studies included that evaluated smoking cessation interventions in the oncology population. In addition, the PC studies were well designed and therefore important to include as part of the review.

The studies were divided into 2 groups: short follow-up time (mean, 5 weeks) and longer follow-up time (6 months). The previous systematic review showed an OR of 1.07 (95% CI, 0.567-2.02; P = .836) for the short-term group and 1.20 (95% CI, 0.801-1.79; P = .381) for the long-term group. It was anticipated that the OR in the updated review would favor a statistically significant benefit for the cessation intervention with more studies that evaluated combination interventions. The pooled OR in the new review for the short-term follow-up group was 1.54 (95% CI, 0.909-2.64; P = .108) for patients in the shorter follow-up group and 1.31 (95% CI, 0.931-1.84; P = .120) for the long-term follow-up group. The ORs in the new study are slightly more favorable for cessation interventions; however, the differences between cessation interventions and usual care are still not statistically significant in both groups.

Long-term abstinence is an important clinical outcome for cessation interventions.²⁸ Longer follow-up time was believed to more accurately reflect the success or failure of an intervention by Fiore et al.²⁰ They described that the 6-month follow-up following the quit date should be the standard follow-up duration in clinical trials as patients who plan to smoke again will do so by 6 months. Thus, in this systematic review, the 2 groups of follow-up times were evaluated separately to accurately reflect the possible differences in quit rates. Although including such diverse studies may be considered a potential weakness, excluding studies with a shorter follow-up would have eliminated a significant number of studies. Furthermore, studies with shorter follow-up should be incorporated to reflect the possible realities of health care counseling for smoking cessation where these patients may not be followed on a long-term basis with regard to continued cessation practices.

In addition, the settings in which the cessation methods were offered are also different. Studies in the literature have indicated that the most successful period to offer cessation intervention is at the time of cancer diagnosis.^4,9,29 Reports in the literature demonstrate that major surgery is also another important teachable moment for smoking cessation.^76,77 The studies, which were included in the systematic review, had interventions in various settings, including the perioperative period and in the clinic. Subgroup analysis demonstrated that the perioperative period had a pooled OR of 2.31 (95% CI, 1.32-4.07). Our study reinforces the findings in the literature of the perioperative period being an essential teachable moment.

Pharmacotherapy for smoking cessation includes NRT, bupropion (norepinephrine-dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist), and varenicline (nicotine receptor partial agonist). Stead et al⁷⁸ analyzed data on more than 50,000 participants comparing any type of NRT with placebo or a non-NRT control group and reported that NRTs increase the rate of quitting by 50% to 70%, regardless of setting. Bupropion was initially marketed as an antidepressant but was subsequently discovered to be efficacious as a smoking cessation aid. Varenicline, marketed as Chantix in the United States and Champix in Canada, showed such promise in early randomized double-blind, placebo-controlled studies that the US Food and Drug Administration (FDA) fast tracked its review and approved the drug in May 2006; it became available for sale in August 2006.⁷⁹ In a recent Cochrane systematic review, Cahill et al⁸⁰ reported standard dosing of varenicline to increase the chances of successful long-term smoking cessation between 2- and 3-fold when compared with pharmacologically unassisted quit attempts. Despite the success of this pharmacotherapy, adverse effects include suicidal ideation and suicide (FDA-issued warning in 2007) and cardiovascular effects (FDA-issued warning in 2011).^81,82 Prescribers must therefore be prudent when evaluating patient suitability for this treatment.

Biochemical verification of smoking status was conducted using breath carbon monoxide (CO) testing, urine cotinine levels, or saliva cotinine levels. Cotinine is the primary metabolite of nicotine and has a long half-life. It may be a more accurate marker for smoking than breath CO as it would be able to detect light or occasional smoking.⁶⁸ The liver converts 75% of nicotine into cotinine by the enzyme cytochrome P450 2A6. Urine cotinine and saliva cotinine have a half-life of 16 hours on average.⁸³ The major limitation of cotinine is that, due to its long half-life, it cannot discriminate between short-term abstinence of less than 24 hours and continued smoking.⁸⁴ Breath CO is the most rapid and noninvasive assessment of smoking cessation. Breath CO, though, has a half-life of only 2 to 3 hours; thus, the sensitivity and specificity can be affected, as it is only sensitive to recent smoking since CO.

Not all studies performed biochemical verification of tobacco cessation. Consequently, our pooled rates were calculated for self-reported tobacco cessation. Our review demonstrates that 91.9% of patients who reported quitting smoking on self-reported questionnaires had in fact quit smoking on biochemical verification. Thus, biochemical validation demonstrates that self-reported rates may be slightly elevated. However, it is not expected that these self-reported rates would bias the review toward a negative result.

Based on the review, the ideal smoking cessation intervention would be initiated in the preoperative period prior to major oncological surgery and continued in the postoperative period. The ideal cessation strategy would include both nonpharmacological interventions such as counseling, therapy, and reading material as well as pharmacological interventions, specifically both nicotine replacement therapy and varenicline.

The individual studies may not be powered to demonstrate the beneficial effects of smoking cessation. Thus, the meta-analysis was conducted to increase the statistical power of the individual studies and improve the precision of results. The pooled studies looked at nearly 1700 patients. The meta-analysis, though, is unable to detect a statistically significant effect of smoking cessation interventions even though the individual studies indicate a favorable effect of smoking cessation. Smoking cessation may have only a small effect, and thus when the studies are pooled, it is not detected through the analysis. The perioperative period seems the most ideal time to counsel patients on smoking cessation.

Conclusion

The systematic review and meta-analysis demonstrate that tobacco cessation interventions in the oncology population in both the long-term and short-term follow-up groups are not statistically significant when compared with usual care. The perioperative period, though, may be an important teachable moment for smoking cessation in oncology patients, as demonstrated through the meta-analysis.

Studies in the literature, though, have identified that tobacco smoking is a well-established risk factor for the development of many malignancies, including those found in the head and neck and thoracic regions, and increases the risk of oncology treatment failure rates and second primary tumors.¹

In theory, tobacco cessation strategies should be an integral part of oncology treatment plans. Tobacco cessation remains, however, a challenging issue in the oncology population. Collaboration within the health care team is paramount in implementing a smoking cessation intervention. The review demonstrates that future research is needed to continue to explore and investigate novel and known methods of smoking cessation to better translate the perceived benefits of tobacco cessation in the oncology population.

Author Contributions

Smriti Nayan, conception and study design, acquisition of data, interpretation of data, manuscript drafting and final approval of draft; Michael K. Gupta, conception and study design, acquisition of data, statistical analysis and interpretation of data, manuscript final approval of draft; Julie E. Styrchowsky, manuscript drafting and final approval of draft; Doron D. Sommer, conception and design, acquisition of data, interpretation of data, manuscript drafting and final approval of draft.

Disclosures

Competing interests: None.

Sponsorships: None.

Funding source: None.

Footnotes

No sponsorships or competing interests have been disclosed for this article.

This article was presented at the 2012 AAO-HNSF Annual Meeting & OTO EXPO; September 9-12, 2012; Washington, DC.

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