Clinical Insights: April 2015
CE lesson worth 1.0 contact hours that are intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
STATEMENT OF NEED
The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.
Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
OVERALL EDUCATIONAL OBJECTIVES
Upon completion, participants should be able to:
- Describe new preventive options and treatments for cancer patients
- Identify options for individualizing the treatment for cancer patients
- Review new evidence to facilitate survivorship and supportive care for cancer patients
Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. CBRN credit is not accepted by the Michigan and Utah State licensing boards.
The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.
METHOD OF PARTICIPATION
- Read the articles in this section in its entirety.
- Go to www.dannemiller.com/onn-Apr-2015
- Complete and submit the CE posttest and activity evaluation.
- Print your Certificate of Credit.
This activity is provided free of charge to participants.
Managing Lymphedema: Educate, Assess, and Intervene Quickly
Moving early to diagnose and treat lymphedema after breast cancer treatment can prevent it from becoming more severe or possibly even reverse it. Yet a consistent way of defining lymphedema, measuring it, and identifying those most at risk remains elusive in practice.
While debate and research on these issues continue, clinicians should nevertheless make early education, assessment, and intervention a priority, urged Sarah McLaughlin, MD, during her presentation at the Miami Breast Cancer Conference February 26, 2015.
“Mild swelling is actually important,” she said. “If you follow these patients with mild swelling, about 50% will progress to a much more severe form—we need to intervene early.”
FLymphedema is a common but under-reported, long-term, chronic side effect of breast cancer treatment affecting approximately 1 in 5 women, said McLaughlin, an associate professor of Surgery at the Mayo Clinic in Jacksonville Florida. In addition to the negative impact on quality of life, it has financial implications as well, she noted. One study found sizeable cost savings associated with addressing breast cancer—related lymphedema (BCRL) using a prospective surveillance model (cost = $636) versus managing late-stage BCRL with a more traditional approach (cost = $3124).
Beyond these numbers, most women treated for breast cancer worry about lymphedema: “They start worrying early about whether or not they are going to get it, and they are pretty persistent in the degree of worry they have,” McLaughlin continued.
“In an ideal world, we would be able to identify which of our patients are actually at risk of developing lymphedema,” she said, but the research isn’t there yet. Even the definition of lymphedema is controversial: “When you read the studies, you have to recognize that everyone defines this differently, they quantify it differently,” and the timing of follow-up assessments also varies.
McLaughlin and colleagues conducted a study involving 120 patients who had undergone either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) to determine which group was more likely to develop lymphedema. In their analysis, they defined lymphedema as >10% volume change from baseline relative to the contralateral upper extremity. Although incidence was similar between the two groups at 6 months, it was higher at 12 months—19% in the ALND arm versus 3% in the SNLB group.1
The study also underscored two important clinical considerations in the prevention and treatment of lymphedema: upper extremity volumes fluctuate, and there is a period of latency before the condition develops. “The critical element is that these patients must have baseline and follow-up measurements,” said McLaughlin.
Other research has shown that after 1 year of follow-up, the rate of lymphedema in women who received an intervention involving education, manual lymphatic drainage, scar massage, and progressive range-of-motion shoulder exercises was 7%, compared with 25% in those who received education only.2
Further research to validate such intervention strategies and improve risk stratification for lymphedema is ongoing, along with studies on a potential role for surgical procedures in preventing or reversing it.
In the meantime, McLaughlin stresses the benefits of exercise to all of her patients, which has been shown to reduce the number and severity of exacerbations. She also urged colleagues not to overlook the importance of subjective clinical assessment alongside consistent application of recommended objective measurements. Citing a case from her own practice where a woman with normal arm measurements and bioimpedance still had noticeable isolated swelling in her right hand, she said: “Clinicians can’t rely on these in the absence of examining the patient.”
- McLaughlin SA, Bagaria S, Gibson T, et al. Trends in risk reduction practices for the prevention of lymphedema in the first 12 months after breast cancer surgery. J Am Coll Surg. 2013;280(3):380-389.
- Torres Lacomba M1, Yuste Sánchez MJ, Zapico Goñi A, et al. Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial. BMJ. 2010; doi: 10.1136/bmj.b5396.
Study Suggests Lung Cancer Screening Criteria May Not Capture All Smokers Who Need It
Eligibility criteria set by the Centers for Medicare & Medicaid Services (CMS) for coverage of low-dose computed tomography (LDCT) for individuals deemed at high risk for lung cancer may actually exclude many potential lung cancer patients who would benefit from screening, according to a new study.
The findings, published in the Journal of the American Medical Association, indicate that efforts to get long-term smokers to quit in recent decades make some former long-term smokers ineligible for screening, because they have not smoked for more than 15 years.
In the study, Ping Yang MD, PhD, and colleagues at the Mayo Clinic in Rochester, Minnesota, evaluated trends in the proportion of patients with lung cancer who meet the US Preventive Services Task Force (USPSTF) criteria as being at high risk for lung cancer. CMS used the USPSTF criteria as the basis for its coverage determination.
Researchers looked at 140,000 residents in Olmstead County, Minnesota, aged 20 or older, from 1984 through 2011. All confirmed cases of lung cancer were identified using the Rochester Epidemiology Project database, adjusting for age and gender distribution in the US population in 2000.
The proportion of cases meeting USPSTF criteria was identified and represented asymptomatic adults aged 55 to 80 years with a 30 pack—year smoking history. This means the person smoked the equivalent of one pack a day for 30 years; a person could also have smoked two packs a day for 15 years. To be screened, a person must be a current smoker or have quit within the past 15 years. Under the Medicare criteria, the age cutoff for LDCT coverage is 77 years.
Researchers identified 1351 patients with a new diagnosis of primary lung cancer between 1984 and 2011. However, the proportion of patients with lung cancer who smoked more than 30 pack years declined, and the proportion of former smokers, especially those who quit more than 15 years ago, increased.
Of note, the share of lung cancer patients meeting the USPSTF criteria declined over time, with 57% of patients eligible for screening from 1984 to 1990 and only 43% eligible from 2005 to 2011. The dropoff in eligibility was greater among women—from 52% to 37%; for men, the dropoff was 60% to 50%.
“Our findings may reflect a temporal change in smoking patterns in which the proportion of adults with a 30 pack—year smoking history and having quit within 15 years declined,” the authors wrote. “The decline in the proportion of patients meeting USPSTF high-risk criteria indicates that an increasing number of patients with lung cancer would not have been candidates for screening. More sensitive screening criteria may need to be identified while balancing the potential harm from computed tomography.”
CMS’ decision to screen current and former smokers for lung cancer was based on the results of the National Lung Screening Trial protocol, which found that patients who received screening had a 15% to 20% lower risk of dying from lung cancer; results published in 2013 showed that targeting screening toward those at greatest risk produced the most effective results.
Wang Y, Midthun DE, Wampfler JA, et al. Trends in the proportion of patients with lung cancer meeting screening criteria. JAMA. 2015;313(8):853-855..
Mari Damhof, RN, BSN, OCN, ONN
Head, Neck, and Lung Care Coordinator
Coborn Cancer Center
St. Cloud, MN
MCancer research continues to provide us with information on cancer—from risk factors that might increase our chances of having cancer, screenings for early detection of cancer, and new treatment options for improved long-term survival and even cure.
Primary screenings exist for colon, cervical, breast, and prostate cancers. Early detection means less invasive treatment and increased opportunity for a cure. Research has shown that for high-risk lung cancer, individuals who had routine CT scans had as much as a 20% lower mortality rate.
Currently, the only screening for lung cancer is the low-dose CT scan. The USPSTF criteria for high-risk lung cancer are asymptomatic adults aged 55 to 80 years with a 30 pack—year smoking history which could include smoking two packs a day for 15 years. Smokers who stopped smoking more than 15 years prior are ineligible for low-dose CT lung cancer screenings under the CMS guidelines.
This study from the Mayo Clinic looked at 1351 individuals with a new primary lung cancer diagnosis from 1984 to 2011 and evaluated trends in those who would have met the criteria for high-risk lung cancer. This study showed that the number of 30 pack—year smokers was declining and the number who had quit smoking for more than 15 years was increasing and made up the larger group of new lung cancer diagnoses.
As a result of this changing trend in the smoking population, changing the screening guidelines may also be in order to effectively use low-dose CT scans to save more lives in the lung cancer population.
Other risk factors for lung cancer, such as having other lung diseases or a family history, can increase an individual’s risk of lung cancer, yet are not included in the high-risk screening because there is no reimbursement at this time. As screening tools improve for lung cancer, so will the early diagnosis of lung cancer and survival rates.
Prior Cancer History Should Not Exclude Patients With Advanced Lung Cancer From Clinical Trials
Results of a new study may help boost lung cancer clinical trial enrollment. Researchers at the UT Southwestern Medical Center have found that previously having cancer does not impact clinical outcomes in lung cancer patients, according to the study, which was published in the Journal of the National Cancer Institute.
“When it comes to clinical trial eligibility, a history of prior cancer should not count against you,” according to senior author David Gerber, MD. “For patients with advanced lung cancer, previous cancer does not adversely affect survival, regardless of the type, stage, or timing of the prior cancer.”
The National Cancer Institute (NCI) estimates that more than 14 million people in the United States have a history of cancer, but there are currently fewer than 5% of adults with cancer participating in clinical trials here.
Gerber, associate professor of Internal Medicine, Division of Hematology and Oncology, at the Harold C. Simmons Comprehensive Cancer Center, said that up to 18% of lung cancer patients are excluded from clinical trials solely based on the fact that they have a history of prior cancer.
“This longstanding and widespread practice reflects concerns that lung cancer patients with a prior cancer would have worse outcomes,” he said. “In the current study, these patients’ outcomes were as good—or even better—than those with no previous cancer diagnosis.”
For the study, researchers analyzed 102,929 patients over the age of 65 who were diagnosed with stage IV lung cancer between1992 and 2009. Of these patients, 14.7% had a history of prior cancer.
Of those with a prior cancer, 76% were diagnosed at stages I, II, or III, and most were diagnosed less than 5 years prior to their lung cancer diagnosis. Among women analyzed in the study, the most common prior cancers were breast, gastrointestinal, and gynecologic, whereas the most common prior cancers for men were prostate, other genitourinary cancers, and gastrointestinal cancers.
The study found that patients with prior cancer had 10% overall survival and 20% better lung cancer—specific survival than those with no previous cancer diagnosis.
Researchers hypothesized that the reason prior cancer patients had superior survival has to do with a lead-time bias rather than a biologic advantage.
“The clinical and radiographic surveillance related to the prior cancer may result in earlier diagnosis of the stage IV lung cancer. This shift leads to longer documented survival times,” said Gerber.
Nonetheless, the knowledge from this study provides key data to help change clinical trial enrollment.
“Modifying the policy for clinical trial inclusion could lead to faster accrual of patients, higher trial completion rates, and more generalizable trial results that can help a greater number of patients, ultimately leading to better treatments,” coauthor Ethan Halm, MD, chief of the William T. and Gay F. Solomon Division of General Internal Medicine, and chief of the Division of Outcomes and Health Services Research in the Department of Clinical Sciences at UT Southwestern, said in a statement.
Laccetti AL, Pruitt SL, Xuan L, et al. Effect of prior cancer on outcomes in advanced lung cancer: implications for clinical trial eligibility and accrual [published online ahead of print February 9, 2015] J Natl Cancer Inst.
David Leos, RN, MBA, OCN
Clinical Research Nurse Supervisor
Department of Radiation Oncology
UT MD Anderson Cancer Center
Many articles on the topic of clinical trial accruals make mention of just how few adult patients who could, actually do, go on a clinical trial. The reasons behind this are varied, but those who practice in this setting are probably aware of this fact and that efforts to combat this can be resource-intensive.
Clinicians may also be familiar with the practice of having eligibility criteria that, to some, may seem to run counter to the objective of accruals by preventing someone from participating in a given trial because they have a prior history of cancer.
Of course, many studies allow for a history of in-situ cancers and those that are likely to stay localized, but anything beyond that stage is often verboten. In reading the original article, some might question why the authors would challenge this practice, especially in the setting of advanced-stage disease. After all, won’t allowing a prior diagnosis just confound results for the sake of adding a few more participants?
prior cancer history, this article offers a plausible way to meaningfully increase accrual rates without compromising patient outcomes and study results.
Additionally, this study suggests that there should be more of a concern for the effects of preexisting comorbidities on trial outcomes. For example, renal or liver impairment were much more likely to have an adverse effect on outcomes than was a prior history of cancer. While such conditions can be the result of prior cancer treatment, most studies take these manifestations into account and set certain limits that are monitored on a regular basis. This allows the concern over eligibility factors to shift focus onto prior cancer treatment.
There is compelling evidence provided here that should allow for rethinking the conventional wisdom of an approach that may have done more to hinder rather than advance treatment.
New Approaches Emerge for Treating Acute Lymphoblastic Leukemia, Yet Challenges Remain
The treatment landscape for acute lymphoblastic leukemia (ALL) is changing, pointing to promising new approaches clinicians can use in practice. These include deploying pediatric regimens in the adult setting, recognizing genetic alterations beyond the Philadelphia chromosome that can be manipulated with targeted agents in “Philadelphia-like” disease, and modifying autologous T-cells with new treatment modalities.
This is all good news for patients, said Dan Douer, MD, in reviewing some of the latest ALL research at the 19th Annual Congress on Hematologic Malignancies held February 20-21, 2015. Douer, an attending physician in the Leukemia Service at Memorial Sloan Kettering Cancer Center, cautioned that while “best clinical practice is changing, what we think today also may change,” in a setting where the response rate is low in patients who relapse, and where there is still no standard classification of risk.
Some of the more provocative questions surrounding ALL treatment, he said, include whether it makes sense to shift standard of care at an age around puberty to 21 years, which he deemed “an administrative decision,” not grounded in the latest research.
Another question involves the use of heavily myelosuppressive “AML-like” drugs. He argued that myelosuppression is a side effect and not a goal in ALL, noting that research has demonstrated no added benefit for anthracycline intensification and that nonmyelosuppressive drugs, including steroids and vincristine, elicit a high response rate in adults with ALL.
Douer also explored the question of why asparaginase is underused in adult patients, a decision he attributed to the belief that it is more toxic in adults than in children where research has demonstrated increasing duration of asparaginase improves overall outcomes. “My concern is that this fear, this reluctance, has not gone away.”
Pediatric Protocols in Adults
Douer noted that adult ALL patients have a higher range of biologically unfavorable disease, presenting a particular challenge for clinicians. He reviewed studies conducted over the last several years utilizing “pediatric-inspired” regimens in adults, including early results from the US Intergroup Trial C10403 (CALGB 10403) which were presented at the 2014 ASH Annual Meeting in December.1
This trial involved 296 newly diagnosed adolescent and young adult (AYA) patients (median age = 24 years, range 17-39), the majority (76%) of whom had B-precursor ALL. The study built on research from the successful Children’s Oncology Group (COG) Study AALL0232.2 For the AYA study reported at ASH, the experimental regimen was identical to the standard arm (Capizzi escalating methotrexate plus PEG asparaginase) used in the COG 0232 study.
When this intensive pediatric regimen was used in the AYA group, 2-year overall survival (OS) was 78%, and event-free survival was 66%. Toxicities in the AYA cohort were similar to those experienced by pediatric patients receiving the regimen in the COG 0232 study, including ALT elevation in approximately 50% of patients in both in the AYA and pediatric populations and hyperbilirubinemia (~25%).
Douer and colleagues adapted the COG 0232 regimen to reduce toxicities in a study involving 51 patients (median age = 32 years, range 18- 57) who received six doses of intravenous pegaspargase at 2000 IU/m2 per dose.3 The approach involved longer intervals between doses, more rational synchronization with other chemotherapy drugs to prevent overlapping toxicities, and administration with steroids to reduce hypersensitivity. Complete remission was achieved in 96% of patients, and notably, said Douer, most patients entered complete remission after one cycle of therapy.
Investigators reported 7-year disease-free and OS rates of 58% and 51%, respectively. Douer added that for standard-risk patients, OS was 74% and for high-risk patients, 40%.
The most common grade 3/4 asparaginaserelated toxicities were lengthy hyperbilirubinemia (31%) and transaminitis (63%), and these occasionally resulted in treatment delays.
“What’s really emerging now are the liver toxicities,” said Douer, prompting many physicians to discontinue use of the drug. He stressed that these toxicities occur mostly after the first dose and may last as long as 1 month, but, “if you continue giving the drug, the toxicity doesn’t necessarily recur after subsequent doses.”
Douer presented some potential strategies for addressing liver toxicity, including experimental data from a study of the effect of L-asparaginase on rat livers. The study determined that the therapy induced severe toxicity in fatty livers, but toxicity was low in normal livers. Moreover, L-carnitine had the potential to ameliorate Lasparaginase— induced hepatotoxicity in patients with preexisting liver disorders.4
“The most important thing is to know how to give asparaginase,” he said; administration guidelines exist, including premedication with hydrocortisone, early identification and treatment of pancreatitis, as well as treatment of thrombosis with oral anticoagulants and of hypertriglyceridemia with gemfibrozil.
Philadelphia+ and “Ph-like” ALL
Before the TKI era, there was no cure for Philadelphia+ (Ph+) ALL without transplant, Douer noted, and the TKI imatinib when combined with chemotherapy has shown efficacy in a number of studies. When patients are imatinib-intolerant or develop resistance, second- and third-generation TKIs can be used, eg, dasatinib, nilotinib, ponatinib. The ideal chemotherapy backbone is unclear, he added, and oncologists tend to use their own “favorite,” typically hyper-CVAD or BFM. Some studies show that prednisone with dasatinib has a high complete remission rate, and the question of allogenic BMT remains open.
“Ph-like” ALL has a gene expression profile similar to Ph+ ALL but without the chromosomal abnormalities. It increases with age and is characterized by a higher white blood cell count, a higher rate of minimal residual disease, and worse outcomes. Research published in The New England Journal of Medicine last fall identified a number of subgroups of kinase genetic alterations. 5
“What’s important,” said Douer, “is that all of these can be targeted by FDA-approved drugs,” such as dasatinib, ruxolitinib, and crizotinib, and studies have demonstrated strong preclinical evidence and encouraging anecdotal clinical responses with this agents.
Blinatumomab and CAR-T Technology
The third breakthrough in ALL treatment involves modifying autologous T cells to kill B ALL cells. In a phase II study presented at the 2014 ASCO Annual Meeting, the efficacy of single-agent blinatumomab was confirmed in a difficult-to-treat population with relapsed/ refractory ALL (NCT01466179).6 In this trial, 43% of patients achieved a complete response (CR) or CR with partial hematological recovery within the first two cycles. “Although this is not a curable approach, you get a reasonably good overall survival,” Douer said, adding that one practical drawback of this therapy is that it is 24-hour infusion over 28 days.
A different way of modifying T cells is through chimeric antigen receptor (CAR)-T technology, and Douer highlighted two recent studies demonstrating the potential of this approach. The first, presented at ASH 2014, reported that CAR-T therapy achieved an 87% CR among the 28 patients enrolled in the study (median age 55, range 23-74 years) and an OS of 57% at 6 months.7 In the other trial involving 30 patients (25 children and 5 adults), the overall CR was 90%, and 6-month OS was 78%.8 Douer noted that most of the responses in these two studies are “deep, with molecular remission.”
A principal concern with CAR-T therapy is cytokine release syndrome (CRS), and it is associated with the patient’s tumor burden, Douer explained. CRS is marked by fever for 3 or more days, significant cytokine elevation, and at least one clinical sign (eg, hypotension, hypoxia, neurologic changes [mental change, seizures]). Treatment involves intensive support, the I-6 inhibitor tocilizumab, and steroids.
In an overall assessment of the two therapies, Douer, said, “blinatumomab is not curative, CAR-T cell therapy may be, but the toxicity is much higher.”
- Stock W, Luger SM, Anjali S, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of US Intergroup Trial C10403. Presented at: 2014 ASH Annual Meeting. Abstract 796.
- Larsen EC, Salzer WL, Devidas M, et al. Comparison of high-dose methotrexate (HD-MTX) with Capizzi methotrexate (C-MTX) plus asparaginase (C-MTX/ASNase) in children and young adults with high-risk acute lymphoblastic leukemia (HR-ALL): A report from the Children’s Oncology Group Study AALL0232. Presented at: 2011 ASCO Annual Meeting. Abstract 3.
- Douer D, Aldoss I, Lunning MA, et al. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):905-911.
- Rosemann A, Afify M, Panse J, et al. L-carnitine ameliorates L-asparaginase- induced acute liver toxicity in steatotic rat livers. Chemotherapy. 2013;59(3):167-175.
- Roberts KG, Li Y, Paine-Turner D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005-1015.
- Topp MS, Goekbuget N, Selwyn Stein A, et al. Confirmatory open-label, single-arm, multicenter phase 2 study of the BiTE antibody blinatumomab in patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL). Presented at: 2014 ASCO Annual Meeting. Abstract 7005.
- Park JH, Riviere I, Wang X, et al. 382 CD19-Targeted 19-28z CAR Modified Autologous T Cells Induce High Rates of Complete Remission and Durable Responses in Adult Patients with Relapsed, Refractory B-Cell ALL. Presented at: 2014 ASH Annual Meeting. Abstract 382.
- Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507-1517.
Head and Neck Cancer
Smoking, Alcohol Use Affect Feeding Tube Duration in Head and Neck Cancer Patients
A new study has found that current smoking and heavy alcohol consumption appear to be risk factors for prolonged use of a gastrostomy tube (GT, feeding tube) in patients with head and neck cancer who are undergoing radiotherapy or chemoradiotherapy.
The study, published online by JAMA Otolaryngology— Head & Neck Surgery, found that current smoking and current heavy alcohol consumption were significant predictors of GT persistence.
“Our results would support advising patients with head and neck SCC undergoing radiotherapy or chemoradiotherapy to avoid smoking and excess alcohol consumption during treatment,” the authors wrote in the study.
Although chemoradiation is a well-established treatment for advanced head and neck cancer, its toxic effects can compromise eating and result in weight loss and malnutrition. Because of this, many institutions recommend prophylactic GT insertion before starting treatment.
Study authors noted that little research has been conducted on the impact of modifiable risk factors on duration of feeding tube use and GT dependence.
Patrick Sheahan, MB, MD, FRCSI, of the South Infirmary Victoria University Hospital in Cork, Ireland and coauthors enrolled 104 patients with squamous cell cancer of the head and neck into the study. All of the enrolled patients were undergoing treatment with either chemoradiation (n=84) or radiotherapy alone (n =20).
Results showed that the median duration of GT use was 9 months, and the rate of GT use at 12 months was 35%. Heavy current alcohol consumption was defined as someone who drank every day, drank more than a specified amount per week, or had a history of alcoholism or alcohol- related illness and was still drinking.
Current smoking (hazard ratio [HR] = 0.47; 95% CI, 0.27-0.81; P = .01) and current heavy alcohol consumption (HR = 0.55; 95% CI, 0.32- 0.97; P = .04) were significant predictors of GT persistence. However, on multivariate analysis, only current smoking remained significant (HR = 0.53; 95% CI, 0.30-0.94; P = .03).
The authors postulated that smoking and drinking have an effect on prolonged GT use because nicotine may suppress appetite, causing patients to make less of an effort to resume full eating, and smoking and drinking may cause patients to feel less motivated to resume eating after treatment.
Although it seems that these vices can lead to prolonged GT use, “to determine whether stopping smoking and drinking can shorten duration of GT use will require further data from prospective studies,” the authors concluded.
O’Shea R, Byrne H, Tuckett J, et al. Impact of current smoking and alcohol consumption on gastronomy duration in patients with head and neck cancer undergoing definitive chemoradiotherapy [published online ahead of print March 19, 2015] JAMA Otolaryngol Head Neck Surg.