Pretreatment Quality of Life Predicts for Locoregional Control in Head and Neck Cancer Patients: A Radiation Therapy Oncology Group Analysis

doi:10.1016/j.ijrobp.2007.06.024

International Journal of Radiation OncologyBiologyPhysics

Volume 70, Issue 2, 1 February 2008, Pages 353-360

https://doi.org/10.1016/j.ijrobp.2007.06.024 Get rights and content

Purpose

To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional control (LRC) and/or overall survival (OS).

Methods and Materials

HRQOL questionnaires, using a validated instrument, the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), version 2, were completed by patients before the start of treatment. OS and LRC were the outcome measures analyzed using a multivariate Cox proportional hazard model.

Results

Baseline FACT-H&N data were available for 1,093 patients and missing for 417 patients. No significant difference in outcome was found between the patients with and without baseline FACT-H&N data (p = 0.58). The median follow-up time was 27.2 months for all patients and 49 months for surviving patients. Multivariate analyses were performed for both OS and LRC. Beyond tumor and nodal stage, Karnofsky performance status, primary site, cigarette use, use of concurrent chemotherapy, and altered fractionation schedules, the FACT-H&N score was independently predictive of LRC (but not OS), with p = 0.0038. The functional well-being component of the FACT-H&N predicted most significantly for LRC (p = 0.0004).

Conclusions

This study represents, to our knowledge, the largest analysis of HRQOL as a prognostic factor in locally advanced head and neck cancer patients. The results of this study have demonstrated the importance of baseline HRQOL as a significant and independent predictor of LRC in patients with locally advanced head and neck cancer.

Introduction

In recent years, health-related quality-of-life (HRQOL) studies have assumed increasing importance in medicine, in general, and in cancer trials, in particular. HRQOL endpoints could be critical in interpreting the results of trials, identifying potential interventions, and guiding physicians toward patient preferences (1). The timing and frequency of collecting HRQOL data for a patient enrolled in a clinical trial depends on the hypothesis being tested, the natural disease course, the treatment protocol, and its anticipated side effects (2). A baseline or pretreatment HRQOL assessment is critical to determine whether the treatment groups being studied differ in pretreatment HRQOL. Importantly, the baseline HRQOL can predict for treatment outcome in terms of locoregional control (LRC) and/or overall survival (OS) 3, 4, 5, 6, 7, 8. Thus, the pretreatment HRQOL often serves as a prognosticator beyond the traditional factors, such as stage, grade, or performance status.

The Functional Assessment of Cancer Therapy-Head and Neck, version 2 (FACT-H&N), a validated disease-specific HRQOL instrument, was completed by patients enrolled in the Radiation Therapy Oncology Group (RTOG) head and neck cancer trials 90-03 and 91-11. The HRQOL data obtained from these patients were analyzed to assess the role of baseline HRQOL as a prognostic variable for LRC and/or survival after accounting for disease and sociodemographic factors. Data from more than 1,000 patients were available for analysis, and this study forms one of the largest series assessing baseline HRQOL and treatment outcome in patients with locally advanced head and neck cancer.

Section snippets

Trial 90-03

RTOG 90-03 was a randomized Phase III trial comparing different radiation fractionation schemes. Patients with Stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, or supraglottic larynx or Stage II-IV carcinoma of the base of tongue or hypopharynx with a Karnofsky performance status (KPS) of ≥60, who were treated between September 1991 and August 1997, were eligible. The patients were randomized to four arms involving different radiotherapy (RT) strategies: Arm 1, standard

Results

At the analysis, 910 of the 1,510 initially analyzed patients had died and 706 had locoregional failure. The median follow-up was 27.2 months (range, 0.13–117.2) for all patients and 49 months (range, 2.5–117.2) for the surviving patients.

Table 1 shows the pretreatment characteristics for the patients analyzed in this study. Baseline FACT-H&N data were available for 1,093 patients (689 patients from RTOG 90-03 and 404 from RTOG 91-11) and missing for 417 patients (303 patients from RTOG 90-03

Discussion

A multitude of therapeutic modalities are now available to treat cancer patients. It is becoming increasingly important in clinical oncology trials to identify the parameters that are able to guide therapy in a manner that is tailored for each individual patient. It has long been appreciated that certain pretreatment variables serve to stratify patients and prognosticate for outcome in terms of LRC and/or OS. These pretreatment variables are useful in deciding the course of therapy. For

References (35)

F. Siddiqui et al.
Quality-of-life outcomes in oncology
Hematol Oncol Clin North Am
(2006)
D. Osoba
Rationale for the timing of health-related quality-of-life (HQL) assessments in oncological palliative therapy
Cancer Treat Rev
(1996)
A. Coates et al.
Quality of life in oncology practice: Prognostic value of EORTC QLQ-C30 scores in patients with advanced malignancy
Eur J Cancer
(1997)
A. de Graeff et al.
Sociodemographic factors and quality of life as prognostic indicators in head and neck cancer
Eur J Cancer
(2001)
A. Montazeri et al.
Quality of life in lung cancer patients: As an important prognostic factor
Lung Cancer
(2001)
S. Kaasa et al.
Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease: The importance of patients' subjective experience of disease and psychosocial well-being
Radiother Oncol
(1989)
K.K. Fu et al.
A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 90-03
Int J Radiat Oncol Biol Phys
(2000)
A. Konski et al.
Continuing evidence for poorer treatment outcomes for single male patients: Retreatment data from RTOG 97-14
Int J Radiat Oncol Biol Phys
(2006)
D. Watkins-Bruner et al.
RTOG's first quality of life study—RTOG 90-20: A phase II trial of external beam radiation with etanidazole for locally advanced prostate cancer
Int J Radiat Oncol Biol Phys
(1995)
D.F. Cella et al.
Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument
Lung Cancer
(1995)

P. Esper et al.

Measuring quality of life in men with prostate cancer using the functional assessment of cancer therapy-prostate instrument

Urology

(1997)

B. Movsas et al.

Pretreatment factors significantly influence quality of life in cancer patients: A Radiation Therapy Oncology Group (RTOG) analysis

Int J Radiat Oncol Biol Phys

(2006)

J.C. Ruckdeschel et al.

Quality of life in lung cancer surgical adjuvant trials

Chest

(1994)

G.F. Buccheri et al.

The patient's perception of his own quality of life might have an adjunctive prognostic significance in lung cancer

Lung Cancer

(1995)

H. Langendijk et al.

The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy

Radiother Oncol

(2000)

J.A. Kramer et al.

Identification and interpretation of clinical and quality of life prognostic factors for survival and response to treatment in first-line chemotherapy in advanced breast cancer

Eur J Cancer

(2000)

F. Efficace et al.

Baseline health-related quality-of-life data as prognostic factors in a phase III multicentre study of women with metastatic breast cancer

Eur J Cancer

(2004)

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Citation Excerpt :
Furthermore, our primary endpoint and secondary endpoints included patient-reported outcomes. Patient-reported outcomes further reduce unintended provider-related bias and are known to have benefits in clinical trial design such as being strong predictors of local control and survival endpoints.36,37 Our study is not without limitations, however.
The purpose of this paper is to determine whether prophylactic gabapentin usage in patients undergoing definitive concurrent chemotherapy and radiation therapy (chemoRT) for oropharyngeal cancer (OPC) improves treatment-related oral mucositis pain, opioid use, and feeding tube (FT) placement.
This double-blind, randomized phase 3 study for patients with locally advanced OPC undergoing chemoRT randomly allocated patients to prophylactic gabapentin (600 mg thrice daily) or placebo. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores over the entire treatment period (baseline to 6 weeks post-radiation therapy [RT] follow-up) with higher scores indicating worse outcomes. Opioid requirements, FT placement, and other patient-reported quality of life (QOL) metrics (Functional Assessment of Cancer Therapy-Head and Neck [FACT-HN] and Patient-Reported Outcomes version of the National Cancer Institute Common Terminology Criteria for Adverse Events [PRO-CTCAE]) were assessed. Lower scores suggested poorer QOL with the FACT-HN questionnaire, and higher scores suggested worse outcomes with the PRO-CTCAE questionnaire. Questionnaires were administered at baseline, weekly during RT, and at 6 weeks post-RT follow-up. Repeated measures analysis of variance was used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon rank sum tests were used to compare averages for the other secondary endpoints. A P value less than .05 was considered statistically significant.
Treatment arms were well balanced overall, including T and N staging and dosimetric variables. There were 58 patients analyzed. No significant difference was found in PROMS scores (mean 29.1, standard deviation [SD] 22.5 vs 20.1, SD 16.8 for gabapentin vs placebo, respectively, P = .11). The FACT-HN functional well-being index had a significant decrease in scores from baseline to follow-up in the gabapentin arm (median −6, interquartile range [IQR] −10.0 to −0.5 vs −1, IQR −5.5 to 3.0, P = .03). PRO-CTCAE scores increased significantly at follow-up for gabapentin (median 6.5, IQR 3.5-11.8 vs 1, IQR −2.0 to 6.0, P = .01). There was no significant difference in average or change in opioid use. FT placement was significantly higher in the gabapentin arm (62.1% vs 20.7%, P < .01).
This study suggests that prophylactic gabapentin is not effective in improving treatment-related oral mucositis symptoms in a select population of patients with OPC undergoing definitive chemoRT.
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To analyze the quality of life (QOL) and performance status (PS) (secondary outcome) in patients with stage III to IV head and neck cancer (HNC) enrolled on a prospective randomized phase 3 trial comparing radiation-cisplatin without cetuximab (CIS) or with cetuximab (CET/CIS). The QOL hypothesis proposed a between-arm difference in Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) total score of ≥10% of the instrument range from baseline to 1 year.
Patients who gave consent to the QOL/PS study completed the FACT-HN, Performance Status Scale for HNC (PSS-HN), and EuroQol (EQ-5D) at baseline through to 5 years. The pretreatment QOL/PS scores were correlated with outcome and p16 status in patients with oropharyngeal cancer (OPC).
Of 818 analyzable patients, the 1-year change from baseline score for FACT-HN total was −0.41 (CIS arm) and −5.11 (CET/CIS arm) (P=.016), representing a 3.2% between-arm change of the FACT-HN total score. The mean EQ-5D index and PSS-HN scores were not significantly different between arms. The p16-positive OPC patients had significantly higher baseline and 1-year scores for PSS-HN, FACT-HN total, physical and functional subscales, and 2-years for the EQ-5D index compared with p16-negative OPC patients. Higher pretreatment PSS-HN diet, PSS-HN eating, FACT-HN, and EQ-5D index scores were associated with better overall survival (OS) and progression-free (PFS) survival on multivariate analysis. Higher baseline FACT-HN total, functional, physical subscale, and EQ-5D index scores were associated with improved OS and PFS in p16-positive OPC patients but not in p16-negative and non-OPC patients.
There was no clinically meaningful difference in QOL/PS between arms. The p16-positive OPC patients had significantly higher QOL/PS than did p16-negative patients. Pretreatment QOL/PS is a significant independent predictor of outcome in locally advanced HNC.
Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Standard Radiation Versus Accelerated Radiation Plus Cisplatin for Locally Advanced Head and Neck Carcinoma: NRG Oncology RTOG 0129
2017, International Journal of Radiation Oncology Biology Physics
To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival.
Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment.
The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to <.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to <.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to <.0001).
The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival.
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2017, International Journal of Radiation Oncology Biology Physics
Human papillomavirus–associated oropharyngeal cancer (OPC) has a favorable prognosis. Current research de-escalates treatment, aiming to improve quality of life (QOL). Understanding the QOL experience with current standard treatment (chemoradiation therapy) provides context for emerging data. We report the impact of p16 status on QOL for patients with stage III or IV OPC undergoing chemoradiation therapy in an international phase 3 trial (TROG 02.02 [HeadSTART]).
A subgroup analysis by p16 status was conducted in patients with OPC treated in a phase 3 randomized trial. The study subset with OPC and known p16 status was mainly from Australasia, Western Europe, and North America. Of 861 participants, 200 had OPC, known p16 status, and baseline QOL data; 82 were p16 negative and 118 were p16 positive. Radiation therapy (70 Gy over a period of 7 weeks) was given concurrently with 3 cycles of either cisplatin (100 mg/m²) or cisplatin (75 mg/m²) plus tirapazamine. QOL was measured with the Functional Assessment of Cancer Therapy–Head and Neck (FACT-H&N) questionnaire at baseline and 2, 6, 12, 23, and 38 months. Because no significant difference in QOL score was observed between arms, results by p16 status are reported with arms combined.
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Patients with p16-positive OPC exhibited better baseline QOL but showed a more dramatic QOL drop with concurrent chemoradiation. Given the favorable prognosis of p16-positive OPC, efforts to reduce the QOL burden of treatment are warranted.

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Clinical InvestigationPretreatment Quality of Life Predicts for Locoregional Control in Head and Neck Cancer Patients: A Radiation Therapy Oncology Group Analysis

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Trial 90-03

Results

Discussion

Hematol Oncol Clin North Am

Cancer Treat Rev

Eur J Cancer

Eur J Cancer

Lung Cancer

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lung Cancer

Urology

Int J Radiat Oncol Biol Phys

Chest

Lung Cancer

Radiother Oncol

Eur J Cancer

Eur J Cancer

Clinical Investigation
Pretreatment Quality of Life Predicts for Locoregional Control in Head and Neck Cancer Patients: A Radiation Therapy Oncology Group Analysis