Portal de Periódicos da CAPES

Quality of Life in Head and Neck Cancer: Where We Are, and Where We Are Going

2017; Elsevier BV; Volume: 97; Issue: 4 Linguagem: Inglês

10.1016/j.ijrobp.2016.12.033

1879-355X

Jolie Ringash,

Oral health in cancer treatment

This issue presents 4 studies reporting the quality of life (QOL) of head and neck cancer (HNC) patients (1Goepfert R.P. Lewin J.S. Barrow M.P. et al.Long-term, prospective performance of the M.D. Anderson Dysphagia Inventory in "low-intermediate risk" oropharyngeal carcinoma after intensity modulated radiation therapy.Int J Radiat Oncol Biol Phys. 2017; 97: 700-708Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 2Ringash J. Fisher R. Peters L. et al.Effect of p16 status on the quality of life experience during chemoradiation for locally advanced oropharyngeal cancer: A sub-study of randomized trial TROG 02.02 (HeadSTART).Int J Radiat Oncol Biol Phys. 2017; 97: 678-687Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 3Truong M.T. Zhang Q. Rosenthal D.I. et al.Quality of life and performance status from a sub-study conducted within a prospective phase III randomized trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for locally advanced head and neck carcinoma: NRG Oncology RTOG 0522.Int J Radiat Oncol Biol Phys. 2017; 97: 687-689Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 4Xiao C. Zhang Q. Nguyen-Tan P.F. et al.Quality of life and performance status from a sub-study conducted within a prospective phase III randomized trial of concurrent standard radiation vs. accelerated radiation plus cisplatin for locally advanced head and neck carcinoma: NRG Oncology RTOG 0129.Int J Radiat Oncol Biol Phys. 2017; : 667-677Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar). It is fitting that these studies have been highlighted by an editorial from the European Organisation for Research and Treatment of Cancer members (5Bottomley A, Bjordal K. Making advances in quality of life studies in head and neck cancer.Google Scholar). In 1980, the European Organisation for Research and Treatment of Cancer was the first oncology cooperative to convene a QOL group and develop a QOL instrument (6Aaronson N.K. Ahmedzai S. Bullinger M. et al.The EORTC core quality-of-life questionnaire: Interim results of an international field study.in: Osoba D. Effect of Cancer on Quality of Life. CRC Press, Boca Raton1991: 185-203Google Scholar). In 1989, the Canadian Cancer Trials Group (formerly the National Cancer Institute of Canada Clinical Trials Group) adopted this instrument and became the first oncology cooperative group to mandate QOL measurement in every phase 3 clinical trial (7Osoba D. The Quality of Life Committee of the Clinical Trials Group of the National Cancer Institute of Canada: Organization and functions.Qual Life Res. 1992; 1: 211-218Crossref PubMed Scopus (61) Google Scholar). Despite these groups' early confidence that patient-reported outcomes (PROs) would add value to trial data, for many years, most studies reporting patient QOL were not experimental but rather observational. Guidelines for "levels of evidence," first proposed by Sackett and Fletcher (8Spitzer W.O. Bayne J.R. Charron K.C. Canadian Task Force on the Periodic Health ExamTask force report: The periodic health exam.Can Med Assoc J. 1979; 121: 1193-1254PubMed Google Scholar), have suggested that well-conducted randomized controlled trials and/or meta-analyses are the least prone to bias and observational studies (cross-sectional, cohort, and case-control designs) have a greater risk of bias, ranked just above expert opinion. For many years, our understanding of the QOL of HNC patients was limited by such designs. Three methodologic issues are especially challenging in QOL research: state-trait confounding, unknown confounders, and missing data. The QOL of an individual at a given time will be the product of that person's inherent personality (a trait) and the effect of transient factors such as disease and treatment (a state). In oncology research, we are often most interested in the effect of the cancer and therapeutic interventions, such that individual trait-based variation (eg, "optimist" or "pessimist") constitutes "noise." The best solution is to internally control by measuring the change in QOL before and after an exposure (eg, cancer treatment). This requires prospective data. Cross-sectional studies cannot determine whether any correlations are truly treatment-related. In a prospective cohort study, we could attempt to measure every possible variable that might influence QOL (eg, age, sex, education, family history of depression); however, we cannot control for unknown confounders. To do so requires randomization. Finally, even in a randomized trial, missing QOL data are rarely "missing at random"—sicker patients are less likely to complete questionnaires, and both internal (comparisons between arms) and external (generalizability) validity suffer when patient compliance with questionnaire completion is poor. QOL research has progressed over time from a focus on instrument development, through an exploration of predictors, to an era of hypothesis testing. Of course, it is artificial to suggest that the more developmental and exploratory work is complete; an excellent example is the report by Goepfert et al (1Goepfert R.P. Lewin J.S. Barrow M.P. et al.Long-term, prospective performance of the M.D. Anderson Dysphagia Inventory in "low-intermediate risk" oropharyngeal carcinoma after intensity modulated radiation therapy.Int J Radiat Oncol Biol Phys. 2017; 97: 700-708Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar) in this issue. Their study was a retrospective pooled analysis of data acquired from 3 single-institution trials, in which swallowing-specific QOL was measured using the MD Anderson Dysphagia Inventory (MDADI). Swallowing and dysphagia have been recognized as pivotal factors in the QOL experience of HNC patients, in particular, those treated with primary radiation therapy (RT), with or without chemotherapy. Although developed in 2001, the MDADI had not previously been validated in human papillomavirus-associated oropharyngeal cancer. The report by Goepfert et al (1Goepfert R.P. Lewin J.S. Barrow M.P. et al.Long-term, prospective performance of the M.D. Anderson Dysphagia Inventory in "low-intermediate risk" oropharyngeal carcinoma after intensity modulated radiation therapy.Int J Radiat Oncol Biol Phys. 2017; 97: 700-708Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar) exemplifies 2 tenets of QOL research: (1) that ongoing methodologic work is required to maximize instrument rigor; and (2) that pooling data between studies can provide opportunities to maximize what is learned from patient input, even when the individual trials were small. Pooling and secondary analysis are important. Patient time and energy produces PRO data. The 3 randomized, phase 3 trials reported in this issue (2Ringash J. Fisher R. Peters L. et al.Effect of p16 status on the quality of life experience during chemoradiation for locally advanced oropharyngeal cancer: A sub-study of randomized trial TROG 02.02 (HeadSTART).Int J Radiat Oncol Biol Phys. 2017; 97: 678-687Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 3Truong M.T. Zhang Q. Rosenthal D.I. et al.Quality of life and performance status from a sub-study conducted within a prospective phase III randomized trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for locally advanced head and neck carcinoma: NRG Oncology RTOG 0522.Int J Radiat Oncol Biol Phys. 2017; 97: 687-689Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 4Xiao C. Zhang Q. Nguyen-Tan P.F. et al.Quality of life and performance status from a sub-study conducted within a prospective phase III randomized trial of concurrent standard radiation vs. accelerated radiation plus cisplatin for locally advanced head and neck carcinoma: NRG Oncology RTOG 0129.Int J Radiat Oncol Biol Phys. 2017; : 667-677Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar) all administered multiple PRO instruments repeatedly. Based on estimates of completion time (9Ringash J. Bernstein L.J. Cella D. et al.Outcomes toolbox for head and neck cancer research.Head Neck. 2015; 37: 425-439Crossref PubMed Scopus (42) Google Scholar), each participant spent upward of 1 to 3 hours completing PROs. Our patients are a valuable resource. Researchers have an ethical responsibility to ensure that their patients' efforts count—by analyzing and publishing data, working to translate and implement findings (10Rouette J. Blazeby J. King M. et al.Integrating health-related quality of life findings from randomized clinical trials into practice: An international study of oncologists' perspectives.Qual Life Res. 2015; 24: 1317-1325Crossref PubMed Scopus (19) Google Scholar), and maximizing knowledge through secondary data sharing (11Bottomley A. Quinten C. Coens C. et al.Making better use of existing cancer data: Patient reported outcomes and behavioural evidence (PROBE): A new international initiative.Eur J Cancer. 2009; 18: 105-107Crossref Scopus (7) Google Scholar). It has been just over a decade since the first phase 3 randomized controlled trial reported QOL results from an HNC population (12Fisher J. Scott C. Scarantino C.W. et al.Phase III quality-of-life study results: Impact on patients' quality of life to reducing xerostomia after radiotherapy for head-and-neck cancer–RTOG 97-9.Int J Radiat Oncol Biol Phys. 2003; 56: 832-836Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar). As of the present issue, a total of 19 prospective, phase 3 randomized controlled trials enrolling only HNC participants and comparing ≥2 interventions using validated QOL instruments have been published (Table 1) (13Ringash J. Waldron J.N. Siu L.L. et al.Quality of life and swallowing experience in a phase III randomized trial of standard fractionation radiotherapy with concurrent cisplatin versus accelerated fractionation radiotherapy with panitumumab in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Canadian Cancer Trials Group HN.6 trial.Eur J Oncol. 2017; 72: 192-199Scopus (16) Google Scholar, 14Ackerstaff A.H. Rasch C.R. Balm A.J. et al.Five year quality of life results of the randomized clinical phase III (Radplat) trial, comparing concomitant intra-arterial versus intravenous chemoradiotherapy in locally advanced head and neck cancer.Head Neck. 2011; 34: 974-980Crossref PubMed Scopus (40) Google Scholar, 15Van Herpen C.M. Mauer M.E. Mesia R. et al.Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPG), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX322).Br J Cancer. 2010; 103: 1173-1181Crossref PubMed Scopus (44) Google Scholar, 16Salas S. Baumstarck-Barrau K. Alfonsi M. et al.Impact of the prophylactic gastrostomy for unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy on quality of life: Prospective randomized trial.Radiother Oncol. 2009; 93: 503-509Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 17Janssens G.O. Langendijk J.A. Terhaard C.H. et al.Quality-of-life after radiotherapy for advanced laryngeal cancer: Results of a phase III trial of the Dutch Head and Neck Society.Radiother Oncol. 2016; 119: 213-220Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 18Nyqvist J. Fransson P. Laurell G. et al.Differences in health related quality of life in the randomized ARTSCAN study: Accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up.Radiother Oncol. 2016; 118: 335-341Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 19Rathod S. Gupta T. Ghosh-Laskar S. et al.Quality-of-life outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT): Evidence from a prospective randomized trial.Oral Oncol. 2013; 49: 634-642Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 20Nutting C.M. Morden J.P. Harrington K.J. et al.Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): A phase 3 multicentre randomized controlled trial.Lancet Oncol. 2011; 12: 127-136Abstract Full Text Full Text PDF PubMed Scopus (1209) Google Scholar, 21Curran D. Giralt J. Harari P.M. et al.Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab.J Clin Oncol. 2007; 25: 2191-2197Crossref PubMed Scopus (211) Google Scholar, 22Pow E.H. Kwong K.L. McMillan A.S. et al.Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial.Int J Radiat Oncol Biol Phys. 2006; 66: 981-991Abstract Full Text Full Text PDF PubMed Scopus (588) Google Scholar, 23Elliott E.A. Wright J.R. Swann R.S. et al.Phase III trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: Results of Radiation Therapy Oncology Group trial 99-13.J Clin Oncol. 2006; 24: 2092-2097Crossref PubMed Scopus (81) Google Scholar, 24Bairati I. Meyer F. Gelinas M. et al.Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer.J Clin Oncol. 2005; 23: 5805-5813Crossref PubMed Scopus (200) Google Scholar, 25Ringash J. Warde P. Lockwood G. et al.Post-radiation quality of life for head & neck cancer patients is independent of xerostomia.Int J Radiat Oncol Biol Phys. 2005; 61: 1403-1407Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 26Duncan G.G. Epstein J.B. Tu D. et al.Quality of life, mucositis and xerostomia from radiotherapy for head and neck cancers: A report from the NCIC CTG HN2 randomized trial of an antimicrobial lozenge to prevent mucositis.Head Neck. 2005; 27: 421-428Crossref PubMed Scopus (119) Google Scholar, 27Stewart J.S. Cohen E.W. Licitra L. et al.Phase III study of gefitinib 250 compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck.J Clin Oncol. 2009; 27: 1864-1871Crossref PubMed Scopus (314) Google Scholar). The intervention was oncologic in 14 and supportive in 5 studies, and QOL was the primary endpoint in 3 and secondary in 16 (Table 2). The interventions ranged from comparisons of different systemic agents with RT (6 trials), different RT approaches (4 trials), RT with different supportive medications (4 trials), RT with or without a systemic agent (2 trials), and 1 trial each comparing feeding strategies during RT, chemoprevention versus placebo, and different chemotherapy regimens for incurable disease. Among these 19 trials, 3 showed significant differences in QOL between treatment arms (Table 3): 2 showed better QOL with intensity modulated RT than with 3-dimensional conformal or field-based RT, and 1 showed worse QOL with accelerated versus conventional RT fractionation. While this still represents a small, slowly growing body of evidence, these trials prove that the collection and analysis of QOL data in HNC patients is feasible and valuable. Today, PRO-based efficacy questions can and should use a randomized trial design.Table 1Published phase 3 RCTs with quality of life comparisons: Primary study dataTrial designYearFirst authorNicknamePatients (n)Disease siteStageControl armExperimental armPrimary analysisCRT studies∗Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions.2016RingashTROG HeadSTART200OPXIII/IVChemo-RTTira/cRTOS2016TruongRTOG0522940OPX, HPX, LXIII/IVChemo-RTCetux/cRTOS2016XiaoRTOG0129743OC, OPX, LX, HPXIII/IVChemo-RTChemo/accelRTOS2016RingashCCTG-HN.6320OC, OPX, LX, HPXIII/IVChemo-RTPmab/accelRTPFS2011AckerstaffRadplat236OC, OPX, HPXUnresectableIV Cisplat/RTIA Cisplat/RTPFS2010van HerpenEORTC 24971/TAX 323358OC, OPX, LX, HPXIII/IV unresectablePF-RTTPF-RTPFS2009SalasFrench GT39"HNC" on cRTIII/IVTGTPGT6-mo SF-36RT studies∗Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions.2016JanssensARCON-Dutch HNS345LXT2-T4N0accRTaccRT/carbogen/nicotinamideLC2016NyqvistARTSCAN750OC, OPX, LX, HPXM0, not T1-T2LXRTaccelRTLRC2013RathodTata-IMRT60OPX, LX, HPXT1-T2N0-N2bM03DCRTIMRTQOL2011NuttingPARSPORT94OPX, HPXM0convRTIMRTLENT/SOMA2007CurranBonner-Cetux424OPX, LX, HPXIII/IVRTRT/CetuxLRC2006PowNPC-IMRT51NPCT2N0-N1convRTIMRTSalivary flow2006ElliottRTOG9913547OC, OPX, LX, HPXIII/IVinstSOCProphylactic trolamineSkin reaction2005BairatiAntioxidants540OC, OPX, LPX, HPXI/IIPlaceboToco/BcarotSecond primary2005RingashPilocarpine130OC, OPX, LX, HPX, NPCM0RT/placeboRT/pilocarpineLASA2005DuncanNCICCTG-HN2138OC, OPX, LX, HPX, NPCM0RT/placeboRT/lozengeMucositis2003FisherRTOG9709249OC, OPXM0RT/placeboRT/pilocarpineUW-QOLChemotherapy studies∗Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions.2009StewartGefitinib486SCHNCMet/recur incurableMethotrexateGefitinib (2 doses)OSAbbreviations: 3DCRT = 3-dimensional conformal radiation therapy; accRT = accelerated fractionation radiation therapy; Bcarot = beta-carotene; Cetux = cetuximab; CGTG = Canadian Cancer Trials Group; Chemo = chemotherapy; Cisplat = cisplatin; convRT = conventional radiation therapy; cRT = chemoradiation therapy; EORTC = European Organisation for Research and Treatment of Cancer; GT = gastric tube; HNC = head and neck cancer; HPX = hypopharynx; IA = intra-arterial; IMRT = intensity modulated radiation therapy; IV = intravenous; instSOC = institutional standard of care; LASA = linear analog scale; LC = local control; LENT/SOMA = late effects of normal tissues/subjective, objective, management, analytic; LRC = locoregional control; LX = larynx; met/recur = metastatic or recurrent; NCICCTG = National Cancer Institute of Canada Clinical Trials Group; NPC = nasopharynx; OC = oral cavity; OPX = oropharynx; OS = overall survival; PF = cisplatin/5-fluorouracil; PFS = progression-free survival; PGT = prophylactic gastric tube; Pmab = panitumumab; QOL = quality of life; RCTs = randomized controlled trials; RTOG = Radiation Therapy Oncology Group; SCHNC = squamous cell head and neck cancer; TGT = therapeutic gastric tube; Tira = tirapazamine; Toco = tocopherol; TPF = docetaxel/cisplatin/5-fluorouracil; TROG = Trans-Tasman Radiation Oncology Group; UW-QOL = University of Washington quality of life.∗ Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions. Open table in a new tab Table 2Published phase 3 RCTs with quality of life comparisons: Quality of life resultsTrial designNicknameQOL instrumentsQOL questionMeasurement timesOutcomeCRT studies∗Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions.TROG HeadSTARTFACT-H&NChange baseline to 6 mo0, 2, 6, 12, 24, 38No differences by armRTOG0522FACT-H&N, EQ5D, PSSHNChange baseline to 12 mo0, ET, 3, 12, 23, 36, 48, 60†FACT-H&N only at 0, 12, and 60 months.P=.016 but not CSRTOG0129HNRQ, Spitzer, PSSHNAUC 0-12 mo0, ET, 3, 12, 24, 36, 48, 60No differences by armCCTG-HN.6FACT-H&N, MDADI, SWAL-QOLChange baseline to 12 mo0, ET, 2, 4, 6, 12, 24, 36No differences by armRadplatQLQC30/HN35Comparison over time0, ET, 3, 12, 24, 60NV vs fatigue; stable 1-5 yEORTC 24971/TAX323QLQC30/HN35, PSSHNQLQC30 6 mo0, end of cycle, 2, 4, 6, 9, after RTFavored TPF but not SS or CSFrench GTSF36, QLQC30/HN35SF36 6 mo0, ET, 6No differences by armRT studies∗Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions.ARCON-Dutch HNSQLQC30/HN35Comparison over time0, ET, 6, 12, 24No differences by armARTSCANQLQC30/HN35Comparison over time0, ET, 3, 6, 12, 24, 60Worse QOL up to 3 moTata-IMRTQLQC30/HN35Comparison over time0, 3, 6, 12, 18, 24Trismus, dry mouthPARSPORTQLQC30/HN35Comparison over time0, 0.5, 3, 6, 12, 18, 24Trend to less dry mouth, not SSBonner-CetuxQLQC30/HN35Comparison over time0, 1, 4, 8, 12No differences by armNPC-IMRTSF36, QLQC30/HN35Comparison over time0, 2, 6, 1212-mo QOL and xerostomia betterRTOG9913Spitzer/HNRQComparison over time0, ETNo differences by armAntioxidantsQLQC30, HNRQComparison over time0, ET, 1More diarrhea with Tx, nil elsePilocarpineHNRQComparison over time0, qw OT, 1, 3, 6No differences by armNCICCTG-HN2QLQC30Comparison over time0, OT 2-4-6, 1, 2, 3No differences by armRTOG9709UW-QOLChange in saliva 0-3 mo0, ET, 3, 6No differences by arm at 3 moChemotherapy studies∗Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions.GefitinibFACT-H&NMean change from baselineNANo differences by armAbbreviations: AUC = area under the curve; CCTG = Canadian Clinical Trials Group; cRT = chemoradiation therapy; CS = clinically significant; EORTC = European Organisation for Research and Treatment of Cancer; ET = end of treatment; FACT-H&N = functional assessment of cancer therapy–head and neck; GT = gastric tube; HNRQ = head and neck radiation therapy questionnaire; IMRT = intensity modulated radiation therapy; LASA = linear analog scale; MDADI = MD Anderson dysphagia index; NA = not available; NCICCTG = National Cancer Institute of Canada Clinical Trials Group; NPC = nasopharyngeal carcinoma; NV = nausea and vomiting; OT = on treatment; PSSHN = performance status scale–head and neck; QLQ-C30/HN35 = EORTC quality of life questionnaire C30 and head and neck 35; QOL = quality of life; qw = weekly; RCTs = randomized controlled trials; RT = radiation therapy; SF36 = Medical Outcomes Study 36-item short-form questionnaire; Spitzer = Spitzer quality of life index; SS = statistically significant; SWAL-QOL = swallowing QOL; TPF = docetaxel/cisplatin/5-fluorouracil; TROG = Trans-Tasman Radiation Oncology Group; Tx = treatment; UW-QOL = University of Washington Quality of Life.∗ Criteria: validated questionnaire, truly randomized, HNC-only studies of supportive interventions.† FACT-H&N only at 0, 12, and 60 months. Open table in a new tab Table 3Published phase 3 RCTs with quality of life comparisons: InterpretationTrial designYearFirst authorNicknameCommentRefInterpretation∗QOL comparisons by arm.CRT studies†Criteria: validated questionnaire, truly randomized, HNC only studies of supportive interventions.2016RingashTROG HeadSTARTSubgroup; SD in QOL up to 1 y by p16 status2Negative2016TruongRTOG0522Subgroup; n=818; compliance 60% at 1 y3Negative2016XiaoRTOG0129Subgroup; n=624 with any QOL at baseline4Negative2016RingashCCTG-HN.613Negative2011AckerstaffRadplatSubgroup; n=20714Negative2010van HerpenEORTC 24971/TAX 323Compliance 50% at 6 mo; later data not analyzed15Negative2009SalasFrench GTExperimental arm better QOL at ET16NegativeRT studies†Criteria: validated questionnaire, truly randomized, HNC only studies of supportive interventions.2016JanssensARCON-Dutch HNSCompliance 60%-78%17Negative2016NyqvistARTSCAN18Positive2013RathodTata-IMRTRT or cRT allowed, balanced by arm19Positive2011NuttingPARSPORT20Negative2007CurranBonner-CetuxCompliance <80% at 8, 12 mo21Negative2006PowNPC-IMRT22Positive2006ElliottRTOG991323Negative2005BairatiAntioxidants24Negative2005RingashPilocarpinePoor compliance wks 5, 6, 725Negative2005DuncanNCICCTG-HN226Negative2003FisherRTOG9709Compliance 50% at 6 mo, 65% at 3 mo12NegativeChemotherapy studies†Criteria: validated questionnaire, truly randomized, HNC only studies of supportive interventions.2009StewartGefitinibCompliance 60%-70%27NegativeAbbreviations: CCTG = Canadian Clinical Trials Group; cRT = chemoradiation thearpy; EORTC = European Organisation for Research and Treatment of Cancer; ET = end of treatment; GT = gastric tube; IMRT = intensity modulated radiation therapy; NCICCTG = National Cancer Institute of Canada Clinical Trials Group; NPC = nasopharyngeal carcinoma; RCT = randomized controlled trial; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; SD = significant difference; TROG = Trans-Tasman Radiation Oncology Group.∗ QOL comparisons by arm.† Criteria: validated questionnaire, truly randomized, HNC only studies of supportive interventions. Open table in a new tab Abbreviations: 3DCRT = 3-dimensional conformal radiation therapy; accRT = accelerated fractionation radiation therapy; Bcarot = beta-carotene; Cetux = cetuximab; CGTG = Canadian Cancer Trials Group; Chemo = chemotherapy; Cisplat = cisplatin; convRT = conventional radiation therapy; cRT = chemoradiation therapy; EORTC = European Organisation for Research and Treatment of Cancer; GT = gastric tube; HNC = head and neck cancer; HPX = hypopharynx; IA = intra-arterial; IMRT = intensity modulated radiation therapy; IV = intravenous; instSOC = institutional standard of care; LASA = linear analog scale; LC = local control; LENT/SOMA = late effects of normal tissues/subjective, objective, management, analytic; LRC = locoregional control; LX = larynx; met/recur = metastatic or recurrent; NCICCTG = National Cancer Institute of Canada Clinical Trials Group; NPC = nasopharynx; OC = oral cavity; OPX = oropharynx; OS = overall survival; PF = cisplatin/5-fluorouracil; PFS = progression-free survival; PGT = prophylactic gastric tube; Pmab = panitumumab; QOL = quality of life; RCTs = randomized controlled trials; RTOG = Radiation Therapy Oncology Group; SCHNC = squamous cell head and neck cancer; TGT = therapeutic gastric tube; Tira = tirapazamine; Toco = tocopherol; TPF = docetaxel/cisplatin/5-fluorouracil; TROG = Trans-Tasman Radiation Oncology Group; UW-QOL = University of Washington quality of life. Abbreviations: AUC = area under the curve; CCTG = Canadian Clinical Trials Group; cRT = chemoradiation therapy; CS = clinically significant; EORTC = European Organisation for Research and Treatment of Cancer; ET = end of treatment; FACT-H&N = functional assessment of cancer therapy–head and neck; GT = gastric tube; HNRQ = head and neck radiation therapy questionnaire; IMRT = intensity modulated radiation therapy; LASA = linear analog scale; MDADI = MD Anderson dysphagia index; NA = not available; NCICCTG = National Cancer Institute of Canada Clinical Trials Group; NPC = nasopharyngeal carcinoma; NV = nausea and vomiting; OT = on treatment; PSSHN = performance status scale–head and neck; QLQ-C30/HN35 = EORTC quality of life questionnaire C30 and head and neck 35; QOL = quality of life; qw = weekly; RCTs = randomized controlled trials; RT = radiation therapy; SF36 = Medical Outcomes Study 36-item short-form questionnaire; Spitzer = Spitzer quality of life index; SS = statistically significant; SWAL-QOL = swallowing QOL; TPF = docetaxel/cisplatin/5-fluorouracil; TROG = Trans-Tasman Radiation Oncology Group; Tx = treatment; UW-QOL = University of Washington Quality of Life. Abbreviations: CCTG = Canadian Clinical Trials Group; cRT = chemoradiation thearpy; EORTC = European Organisation for Research and Treatment of Cancer; ET = end of treatment; GT = gastric tube; IMRT = intensity modulated radiation therapy; NCICCTG = National Cancer Institute of Canada Clinical Trials Group; NPC = nasopharyngeal carcinoma; RCT = randomized controlled trial; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; SD = significant difference; TROG = Trans-Tasman Radiation Oncology Group.