Tolerability, toxicity, and temporal implications of transoral robotic surgery (TORS) on adjuvant radiation therapy in carcinoma of the head and neck.

OBJECTIVES: Overall treatment package time (from surgery to radiotherapy [RT] completion) > 100 days can portend poor outcomes in head and neck cancer. Faster postoperative recovery seen with transoral robotic surgery may decrease treatment duration and toxicity for adjuvant RT and chemoradiation. METHODS: We retrospectively reviewed all patients treated with transoral robotic surgery (n = 124) and adjuvant RT and chemoradiation (n = 33) at our institution for head and neck cancer from April 2007 to December 2011 to determine treatment duration, acute toxicity, and long-term percutaneous gastric tube rates. RESULTS: The median overall treatment time was 86 days and from surgery to RT start was 41 days; median RT duration was 44 days. No wound breakdown or infection occurred during or after RT. Two-year actuarial locoregional control, distant metastasis-free survival, and overall survival rates were 93%, 96%, and 97%, respectively. CONCLUSIONS: Adjuvant RT after transoral robotic surgery for head and neck cancer can be completed safely and in a timely fashion. Longer follow-up and a larger cohort will be needed to determine if this regimen is more effective than traditional surgery followed by adjuvant RT.

Organ preservation for adenoid cystic carcinoma of the larynx.

OBJECTIVES: Two cases of adenoid cystic carcinoma (ACC) of the larynx were treated with chemoradiotherapy (CRT) for organ preservation. We reviewed case series and current literature to contrast the potential role of primary CRT as an organ-sparing modality with standard laryngectomy and radiotherapy in patients with laryngeal ACC. METHODS: Two treatment-naïve patients with laryngeal ACC treated at Dana-Farber Cancer Institute between 2002 and 2007 were identified. Both patients were offered standard laryngectomy followed by adjuvant radiotherapy or organ-sparing treatment modality. RESULTS: Both patients were males, aged 57 and 73. The patients completed a course of combined chemoradiotherapy with weekly carboplatin and paclitaxel and 7-8 weeks of radiotherapy to a total dose of 6,600 and 7,000 cGy over 50 and 57 days, respectively. There were no treatment breaks or delays because of toxicity. The major toxicities reported by both patients, as anticipated, were Grade 3 mucositis, desquamative dermatitis, and severe dysphagia, all of which resolved. Both patients are alive with local regional control and functional larynx; one at 112+ months with pulmonary metastases at 54 months, and the other disease free at 60+ months. CONCLUSIONS: Definitive chemoradiation with weekly carboplatin and paclitaxel may be a potential alternative to the current standard of surgery and radiation for patients with locally advanced laryngeal ACC who request an organ-sparing approach. In this group of patients, salvage laryngectomy may be reserved for those who are locally recurrent or chemoradiotherapy resistant. Although CRT provided long-term local regional control in our two patients, there are evident limitations in obtaining evidence for a determination of treatment of rare diseases. This report provides support for following an organ preservation plan in selected patients.

High Failure Rates in Young Nonsmoker Nondrinkers With Squamous Cell Carcinoma of the Oral Tongue.

OBJECTIVE(S): There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature. METHODS: A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage. RESULTS: Eighty-two patients (38 young, 44 old) were included in this study. Median follow-up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5-year locoregional control (LC) (79.6% vs. 52.5%, p = 0.043) and distant metastasis-free survival (88.1% vs. 61.8%, p = 0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease-specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n = 7), 100% demonstrated in-field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p = 0.004) and the advanced stage was a predictor of DSS (p = 0.03). CONCLUSIONS: Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in-field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1110-1121, 2023.

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus-Associated Oropharyngeal Cancer.

Importance: There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. Objective: To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. Design, Setting, and Participants: This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Main Outcomes and Measures: Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Results: Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. Conclusions and Relevance: This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

A Phase 1 Study of Afatinib in Combination with Postoperative Radiation Therapy with and Without Weekly Docetaxel in Intermediate- and High-Risk Patients with Resected Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: To determine the maximum tolerated dose and tolerability of (1) afatinib in combination with postoperative radiation therapy (PORT) for patients with intermediate-risk squamous cell carcinoma of the head and neck (SCCHN) and (2) afatinib in combination with PORT and weekly docetaxel for high-risk SCCHN. METHODS AND MATERIALS: An open-label, multicenter, 2-cohort, phase 1 dose-escalation trial was conducted using a 3 + 3 design. Eligible patients had definitive surgery for SCCHN, including the oral cavity, oropharynx, larynx, or hypopharynx and had intermediate- or high-risk pathologic features. Afatinib was given for a 1-week lead in before PORT and daily during 6 to 6.5 weeks of PORT with or without weekly docetaxel. The starting dose was 30 mg and could be escalated to 40 mg or de-escalated to 20 mg. The primary objective was to determine the maximum tolerated dose of afatinib with PORT or PORT + docetaxel. RESULTS: Between April 2013 and November 2017, 27 patients were enrolled and started study treatment, including 16 intermediate-risk patients and 11 high-risk patients, all with Eastern Cooperative Oncology Group performance status of 0 to 1. Most patients (n = 25) had oral cavity cancer and were treated to a median total dose of 60 Gy in the intermediate-risk arm and 65 Gy in the high-risk arm. There was 1 grade 4 event, but no deaths. The maximum tolerated dose was not established owing to dose-limiting toxicities (DLTs) in both arms. In the high-risk arm, DLTs were grade 3 mucositis (n = 3) and grade 3 diarrhea/hypokalemia (n = 1). In the intermediate-risk arm, DLTs were grade 3 mucositis (n = 4) and grade 3 diarrhea (n = 2). CONCLUSIONS: Afatinib in combination with PORT for mucosal SCCHN was difficult to tolerate because of grade 3 toxicity, mostly mucositis, in a cohort of patients requiring high-dose PORT to the oral cavity. This regimen may be better tolerated for a non-oral cavity site or if given in a different schedule.

Premature discontinuation of curative radiation therapy: Insights from head and neck irradiation.

PURPOSE: Factors related to premature discontinuation of curative radiation therapy (PDCRT) are understudied. This study aimed to examine causes and clinical outcomes of PDCRT at our institution by investigating the most common anatomical site associated with PDCRT. METHODS AND MATERIALS: Among the 161 patients with PDCRT of various anatomic sites at our institution between 2010 and 2017, 36% received radiation to the head and neck region. Pertinent demographic, clinical, and treatment-related data on these 58 patients were collected. Survival was examined using the life-table method and log-rank test. RESULTS: The majority of patients were male (81%), white (67%), ≥60 years old (59%), living ≥10 miles away from the hospital (60%), single (57%), with Eastern Cooperative Oncology Group score ≥1 (86%), experiencing significant pain issues (67%), and had treatment interruptions in radiation therapy (RT; 66%). The most common reasons for PDCRT were discontinuation against medical advice (33%), medical comorbidity (24%), and RT toxicity (17%). Of the comorbidities leading to PDCRT, 50% was acute cardiopulmonary issues and 43% was infection. The mean follow-up time was 15.9 months, and the 2-year overall survival and disease-specific survival rates were 61% and 78%, respectively. Patients with illicit substance abuse, cardiovascular disease, and Eastern Cooperative Oncology Group score ≥2 had worse survival. A trend toward improved survival with total completed dose ≥50 Gy versus <50 Gy existed (74% versus 44%, respectively; P = .07). CONCLUSIONS: In this largest-to-date, modern analysis of PDCRT, the most common cause of discontinuation was discontinuation against medical advice, which underscores the importance of patient education, optimization of RT symptoms, involvement of social work, and integration of other supportive services early in treatment. Survival remains suboptimal after PDCRT for H&N tumors, with a 2-year overall survival rate of 61%. Completing >50 Gy appears to confer a relative therapeutic benefit.

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment.

OBJECTIVES: Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. MATERIALS AND METHODS: 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. RESULTS: At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p=0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR]=1.81, 95%CI=0.47-6.92). CONCLUSION: This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

Neoadjuvant Therapy in Differentiated Thyroid Cancer.

Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC.

Adjuvant Radiation Therapy Alone for HPV Related Oropharyngeal Cancers with High Risk Features.

BACKGROUND: Current standard of care for oropharyngeal cancers with positive surgical margins and/or extracapsular extension is adjuvant chemoradiotherapy. It is unknown whether HPV+ oropharyngeal cancer benefits from this treatment intensification. OBJECTIVE: To investigate the outcomes of HPV+ patients treated with adjuvant radiotherapy alone when chemoradiotherapy was indicated based on high risk pathological features. They were compared with high risk HPV+ patients treated with adjuvant chemoradiotherapy. METHODS: All high risk HPV+ oropharyngeal cancer patients (9) who received radiotherapy alone were identified. We also identified 17 patients who received chemoradiotherapy as a comparison group. Median follow up time was 37.3 months. RESULTS: No local failures developed in adjuvant radiotherapy group. There was 1 distant recurrence in this cohort and 3 in CRT cohort. Regarding toxicity, 8 (47.1%) chemoradiotherapy patients had >10 lb. weight loss (p = 0.013), despite 75% of them having a percutaneous endoscopic gastrostomy tube placed. No individuals in radiotherapy group experienced a >10 lb. weight loss and none required a gastrostomy tube. CONCLUSIONS: This series provides preliminary evidence suggesting that the omission of concurrent chemotherapy to adjuvant radiotherapy may offer comparative local control rates with a lower toxicity profile in the setting of HPV+ patients with traditional high risk features.

Clinical Outcomes in Patients with Recurrent or Metastatic Human Papilloma Virus-positive Head and Neck Cancer.

BACKGROUND: There are few data regarding the role of human papilloma virus (HPV) in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: A retrospective chart review was carried out using our electronic medical record (EPIC) for all patients diagnosed with HPV-positive R/M HNSCC between 2010 and 2014 with minimum of 6 months of follow-up in order to assess progression-free survival (PFS) and overall survival (OS). RESULTS: We assessed 11 patients who underwent a variety of treatments. PFS and OS were 7 and 34+ months, respectively. Four patients (36%) were still alive and disease-free (median OS of 39+ months). Three disease-free patients had been treated with taxane, platinum and 5-fluorouracil as aggressive curative systemic therapy. Another patient treated with TPF was disease-free for 25 months and died of disease at 42 months. CONCLUSION: Our study demonstrates favorable prognosis for patients with HPV-positive R/M HNSCC and that aggressive systemic treatment can lead to a prolonged disease-free period or possibly cure, even after metastasis.

Clinical characteristics and outcomes of oropharyngeal carcinoma related to high-risk non-human papillomavirus16 viral subtypes.

BACKGROUND: The majority of human papillomavirus (HPV)-related oropharyngeal carcinomas (OPCs) are associated with HPV genotype 16; however, OPC can be associated with other high-risk non-HPV16 genotypes. METHODS: This was a retrospective analysis of patients with high-risk non-HPV16 OPC treated at a single tertiary institution. Sociodemographic and clinical information was obtained by chart review. HPV genotype was determined by polymerase chain reaction (PCR). Baseline data and outcomes were compared between HPV16 and high-risk non-HPV16 groups. RESULTS: High-risk non-HPV16 genotypes accounted for 9% of HPV-related OPC. Of the 27 total high-risk non-HPV16 OPCs, HPV35 was most prevalent (48%). High-risk non-HPV16 OPC presented at a slightly higher age (p = .021) and higher clinical T classification (p = .008) compared to HPV16 OPC, but there was no significant survival difference. CONCLUSION: Clinical characteristics of high-risk non-HPV16 OPC were largely consistent with those of HPV16 OPC. Additional multi-institutional studies will be required to demonstrate conclusively that the favorable prognosis of patients with HPV16 applies to all high-risk HPV types. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1330-1337, 2016.

Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA Detection in Oral Rinses for Human Papillomavirus-Related Oropharyngeal Carcinoma.

IMPORTANCE: Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear. OBJECTIVE: To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study. MAIN OUTCOMES AND MEASURES: Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis. RESULTS: Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months. CONCLUSIONS AND RELEVANCE: Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.

Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer.

Recent Phase III data presented at the American Society of Clinical Oncology (ASCO) 2013 annual conference by Brose et al led to the US Food and Drug Administration (FDA) approval of sorafenib for the treatment of well-differentiated radioactive iodine-resistant metastatic thyroid cancer. This is the second drug in 40 years to be FDA approved for this indication. Recent reviews and a meta-analysis reveal a modest ability to induce a partial remission but substantial ability to halt disease progression. Given the significant activating mutations present in thyroid cancer, many of which are inhibited by sorafenib, the next logical approach may be to combine targeted rational therapies if permitted by collective toxicity profiles. This systematic review aims to summarize the recent Phase II/III data leading to the FDA approval of sorafenib for radioactive iodine therapy differentiated thyroid cancer and highlights recent novel combination therapy trials.

A systematic review of head and neck cancer quality of life assessment instruments.

Although quality of life (QOL) is an important treatment outcome in head and neck cancer (HNC), cross-study comparisons have been hampered by the heterogeneity of measures used and the fact that reviews of HNC QOL instruments have not been comprehensive to date. We performed a systematic review of the published literature on HNC QOL instruments from 1990 to 2010, categorized, and reviewed the properties of the instruments using international guidelines as reference. Of the 2766 articles retrieved, 710 met the inclusion criteria and used 57 different head and neck-specific instruments to assess QOL. A review of the properties of these utilized measures and identification of areas in need of further research is presented. Given the volume and heterogeneity of QOL measures, there is no gold standard questionnaire. Therefore, when selecting instruments, researchers should consider not only psychometric properties but also research objectives, study design, and the pitfalls and benefits of combining different measures. Although great strides have been made in the assessment of QOL in HNC and researchers now have a plethora of quality instruments to choose from, more work is needed to improve the clinical utility of these measures in order to link QOL research to clinical practice. This review provides a platform for head and neck-specific instrument comparisons, with suggestions of important factors to consider in the systematic selection of QOL instruments, and is a first step towards translation of QOL assessment into the clinical scene.