A systematic review of smell alterations after radiotherapy for head and neck cancer.

PURPOSE: To review the current knowledge on radiotherapy associated olfactory dysfunction among head and neck cancer (HNC) patients. METHODS: A systematic review of RT-related olfactory dysfunction in HNC was performed. Searches were conducted in several databases (Medline, EMBASE, CINAHL, CAB Abstracts, SCOPUS, Proquest Dissertations and Theses, PROSPERO, ALLEBM Reviews - Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED). Publications investigating olfactory dysfunction as an explicit side effect of Radiotherapy (RT, or RT-chemo or RT-monoclonal antibodies) were eligible, no limits were applied. RESULTS: Two hundred and twenty-nine papers were screened and 23 met inclusion criteria. CONCLUSIONS: Odor detection, identification and discrimination are olfactory functions impaired after RT for HNC. An RT dose-effect has been calculated for odor identification and odor discrimination. There were no studies of the effect of olfactory dysfunction on weight loss or energy intake among RT-treated HNC patients. To improve our understanding of RT associated olfactory dysfunction among HNC patients, future studies should include a multi-dimensional assessment of olfactory function in a longitudinal design, track other conditions affecting olfaction, assess retronasal olfactory perception, adopt validated self-report tools and explore the impact of olfactory dysfunction on the eating experience of HNC patients.

Physical symptom burden of post-treatment head and neck cancer patients influences their characterization of food: Findings of a repertory grid study.

BACKGROUND AND AIM: Dietary advice for post treatment head and neck cancer (HNC) patients emphasizes food characteristics of nutritional value and texture, and not patients' characterization of food. The aim of this study was to determine patients' characterization of food. METHODS: Repertory grid interviews were conducted with 19 orally-fed HNC patients between 4 and 10 months post-treatment to characterize foods commonly eaten, avoided and eaten sometimes. Patients compared and rated 12 foods using their own descriptors. Data were analyzed by General Procrustes Analysis (GPA). Socio-demographic status, taste and smell alterations, appetite and food intake data were also collected. Patient physical symptom burden was defined by University of Washington-Quality of Life Physical Function domain scores and used to stratify patients with "less physical symptom burden" (n = 11, score ≥ 61.7) or "greater physical symptom burden" (n = 8, score < 61.7). RESULTS: All patients used descriptors of taste, ease of eating, convenience, texture, potential to worsen symptoms and liking to characterize foods. Overall, avoided foods were characterized as having dry texture, while foods commonly eaten were characterized by their ease of eating and low potential to worsen symptoms. Descriptors of nutrition and smell were significant only for patients with greater physical symptom burden. CONCLUSIONS: Physical symptom burden influenced the characterization of foods among post-treatment HNC patients. Nutrition counseling must consider patients' physical symptom burden and the subsequent characterization of food that drive food selection or avoidance to facilitate dietary advice for adequate, appropriate and enjoyable food intake.

The impact of taste and smell alterations on quality of life in head and neck cancer patients.

PURPOSE: Taste and smell alterations (TSAs) are among the most frequent and troublesome symptoms reported by head and neck cancer (HNC) patients after treatment. Little is known about the relationship between TSAs and quality of life (QoL) among HNC patients. The aim of this study was to determine the effect of TSAs on overall QoL among tube-fed and orally fed HNC patients before treatment, at end of treatment and at 2.5-month follow-up. METHODS: Data were collected in a longitudinal study prior to treatment (n = 126), at end of treatment (n = 100) and at 2.5-month follow-up (n = 85). Chemosensory Complaint Score (CCS) and the University of Washington Quality of Life Questionnaire version 3 were used to assess TSAs and QoL, respectively. Generalized estimated equation modeling was used to estimate the effect of CCS on QoL. RESULTS: At end of treatment, QoL and CCS had declined for both tube-fed and orally fed patients and thereafter improved, but not to pre-treatment levels. Neither QoL nor CCS mean scores were different between the two groups at any time point. CCS was a significant predictor of overall QoL (ß = -1.82, p < 0.0001), social-emotional (ß = -1.76, p < 0.0001), physical (ß = -1.12, p < 0.0001) and overall functions (ß = -1.15, p < 0.0001) at a multivariate level. Taste was reported as an important symptom for both tube-fed and orally fed groups at end of treatment and follow-up. CONCLUSIONS: TSAs are an important symptom and an independent predictor of QoL for both tube-fed and orally fed HNC patients. HNC patients need support to manage TSAs, regardless of the method of nutritional intake.

Health care delivery for head-and-neck cancer patients in Alberta: a practice guideline.

BACKGROUND: The treatment of head-and-neck cancer is complex and requires the involvement of various health care professionals with a wide range of expertise. We describe the process of developing a practice guideline with recommendations about the organization and delivery of health care services for head-and-neck cancer patients in Alberta. METHODS: Outcomes of interest included composition of the health care team, qualification requirements for team members, cancer centre and team member volumes, infrastructure needs, and wait times. A search for existing practice guidelines and a systematic review of the literature addressing the organization and delivery of health care services for head-and-neck cancer patients were conducted. The search included the Standards and Guidelines Evidence (sage) directory of cancer guidelines and PubMed. RESULTS: One practice guideline was identified for adaptation. Three additional practice guidelines provided supplementary evidence to inform guideline recommendations. Members of the Alberta Provincial Head and Neck Tumour Team (consisting of various health professionals from across the province) provided expert feedback on the adapted recommendations through an online and in-person review process. Selected experts in head-and-neck cancer from outside the province participated in an external online review. SUMMARY: The recommendations outlined in this practice guideline are based on existing guidelines that have been modified to fit the Alberta context. Although specific to Alberta, the recommendations lend credence to similar published guidelines and could be considered for use by groups lacking the resources of appointed guideline panels. The recommendations are meant to be a guide rather than a fixed protocol. The implementation of this practice guideline will depend on many factors, including but not limited to availability of trained personnel, adequate funding of infrastructure, and collaboration with other associations of health care professionals in the province.

Adaptive radiotherapy using helical tomotherapy for head and neck cancer in definitive and postoperative settings: initial results.

AIMS: To assess whether routine mid-treatment replanning in head and neck squamous cell carcinoma patients results in meaningful improvements in target or normal tissue dosimetry and to assess which patients derive the greatest benefit. MATERIALS AND METHODS: Twenty patients treated with either postoperative chemoradiotherapy or definitive chemoradiotherapy with primary or nodal disease ≥3cm in size were included in this prospective pilot study. Seven patients received adjuvant chemoradiotherapy and 13 received definitive chemoradiotherapy. Patients were planned and treated on a helical tomotherapy system. All patients had a second computed tomography scan after 15 fractions and a new plan based on this was initiated from fraction 20. RESULTS: Relative volume changes between computed tomography scans were: GTV 29%; CTV60 (adjuvant patients) 4%; parotid volume 17.5%; median reduction in neck separation 6-7 mm; weight loss 3%. For the group overall and for the definitively treated patient cohort, respectively, adapted plans resulted in reductions in PTV66 D(1) (0.3Gy, P=0.01 and 0.5Gy, P=0.01); PTV54 D(1) (0.6Gy, P<0.0001 and 0.9Gy, P=0.0002); spinal cord maximum (0.5Gy, P=0.004 and 0.6Gy, P=0.04) and volume of skin receiving ≥50Gy (16 cm(2), P=0.01 and 19 cm(2), P=0.001). Definitively treated patients also had a reduction in mean parotid dose (0.6Gy, P=0.046) and volume of normal tissue receiving ≥50Gy (67 cm(3), P=0.02). Patients with nasopharyngeal carcinoma received the greatest benefits with treatment adaptation with reduction in spinal cord maximum 1.2Gy, mean parotid dose 1.2Gy and parotid V(26) 6.3%. There was no significant benefit for adjuvant patients. Other factors associated with greater benefits were greater weight loss and greater reduction in neck separation and higher T stage. CONCLUSIONS: There is minimal benefit to routine adaptive replanning in unselected patients, and no benefit in adjuvantly treated patients. Patients with nasopharyngeal carcinoma or with greater weight loss or reduction in neck separation did have clinically significant benefits. These patients should be targeted for adaptive strategies.

Implications of radiation dosimetry of the mandible in patients with carcinomas of the oral cavity and nasopharynx treated with intensity modulated radiation therapy.

Intensity modulated radiation therapy (IMRT) is a newer method of delivering highly conformal, salivary gland sparing radiation treatment that is finding increasing applications in head and neck malignancies. However, the radiation dose distribution to the mandible is rarely considered with IMRT, and the potential risks of osteoradionecrosis or osseointegrated implant failure are not well characterized for this modality. In a series of 10 patients with oral cavity and nasopharyngeal cancers who previously underwent IMRT, examination of the three-dimensional mandibular dose distribution was undertaken. The findings indicate a modest potential risk of osteoradionecrosis and osseointegrated implant failure in cases where IMRT optimization constraints are not specifically aimed at sparing the mandibular bone. Significantly higher mandibular doses (P < 0.04) were received in cases of oral cavity as opposed to nasopharyngeal cancers with IMRT. Efforts to optimize IMRT to further reduce doses to the mandible should be considered, and development of software tools to integrate three-dimensional dose distributions into planning of post-radiotherapy osseointegration would be beneficial.

Muscle-invasive transitional cell carcinoma of the urinary bladder: a population-based study of patterns of care and prognostic factors.

PURPOSE: Population-based cancer registries can permit the study of the survivorship of all patients with a particular diagnosis regardless of patterns of referral and practice within a specific geographic distribution. The purpose of this study is to describe the patterns of care, outcome, and prognostic factors for bladder cancer in the northern region of the province of Alberta, Canada, between 1984 and 1993. METHODS AND MATERIALS: Between 1984 and 1993, 184 patients from northern Alberta were identified from the Alberta Cancer Registry as having undergone curative treatment for biopsy-proven muscle-invasive transitional cell carcinoma of the bladder. Data were obtained, by retrospective chart review, regarding the staging, pathology, treatment, and outcome of patients treated in the northern Alberta cities of Edmonton, Grande Prairie, and Red Deer, regardless of the responsible treating institution. The prognostic significance of patient-, tumor-, and treatment-related variables were tested using univariate and multivariate analysis using the Cox proportional-hazard model. RESULTS: As the primary treatment modality, 74 patients (40%) received radical radiotherapy (RT) without surgery; surgery was used alone in 81 patients (44%), and was combined with preoperative or postoperative radiotherapy in 29 patients (16%). Seventy-three (40%) patients also received concurrent, neoadjuvant, or adjuvant chemotherapy. The Kaplan-Meier estimate of median survival was 2.2 years, and the 5-year overall survival was 30%. Univariate analysis demonstrated the prognostic significance of T classification (p < 0.001), lymph node involvement (p < 0.001), complete response to RT (p = 0.001), hydronephrosis (p = 0.017), and vascular/lymphatic involvement (p = 0.035). Multivariate analysis revealed the following to have a significant association with survival: T classification (p = 0.001), lymph node involvement (p = 0.004), complete response to RT (p = 0.054), hydronephrosis (p = 0.019), and use of chemotherapy in the treatment regimen (p = 0.025). CONCLUSION: The strongest prognostic factors in this study were tumor related, and no significant differences in survival were detected between patients treated with primary surgery vs. organ-preservation approaches. A survival advantage associated with the incorporation of chemotherapy into the management schema was detected on multivariate, but not univariate, analysis. Stratification of patients based on tumor characteristics is imperative in clinical trials for invasive bladder cancer. Novel treatment approaches are required to improve survival further in patients with apparently localized disease.

A new approach to dose escalation in non-small-cell lung cancer.

PURPOSE: To describe the radiobiological rationale for dose-per-fraction escalation in non-small-cell lung cancer (NSCLC) and to devise a novel Phase I scheme to implement this strategy using advanced radiotherapy delivery technologies. METHODS AND MATERIALS: The data from previous dose escalation trials in NSCLC are reanalyzed to establish a dose-response relationship in this disease. We also use data relating prolongation in treatment time to survival to compute the potential doubling time for lung tumors. On the basis of these results, and using a Bayesian model to determine the probability of pneumonitis as a function of mean normalized lung dose, a dose-per-fraction escalation strategy is developed. RESULTS: Standard approaches to dose escalation using 2 Gy per fraction, five fractions per week, require doses in excess of 85 Gy to achieve 50% long-term control rate. This is partly because NSCLCs repopulate rapidly, with a 1.6% per day loss in survival from prolongation in overall treatment time beyond 6 weeks, and a cell doubling time of only 2.5 to 3.3 days. A dose-per-fraction escalation strategy, with a constant number of fractions, 25, and overall time, 5 weeks, is projected to produce tumor control rates predicted to be 10%-15% better than 2 Gy per fraction dose escalation, with equivalent late effects. This Phase I clinical study is divided into three parts. Step 1 examines the feasibility of the maximum breath-holding technique and junctioning of tomotherapy slices. Step 2 treats 10 patients with 30 fractions of 2 Gy over 6 weeks and then reduces duration to 5 weeks using fewer but larger fractions in 10 patients. Step 3 will consist of a dose-per-fraction escalation study on roughly 50 patients, maintaining 25 fractions in 5 weeks. Bayesian methodology (a modification of the Continual Reassessment Method) will be used in Step 3 to allow consistent and efficient escalation within five volume bins. CONCLUSION: A dose-per-fraction escalation approach in NSCLC should yield superior outcomes, compared to standard dose escalation approaches using a fixed dose per fraction, for a given level of pneumonitis and late toxicity. Highly conformal radiotherapy techniques, such as intensity modulated radiotherapy (IMRT) and helical tomotherapy with its adaptive capabilities, will be necessary to achieve significant dose-per-fraction escalation without unacceptable lung and esophageal morbidity.

CT-targeted irradiation of the breast and internal mammary lymph nodes using a 5-field technique.

PURPOSE: To develop an effective and resource-efficient radiotherapy technique to treat the breast and regional nodes, including the ipsilateral internal mammary nodes. METHODS AND MATERIALS: Eighty female patients who underwent MRI scans for a variety of indications had coronal, T1-weighted images of the chest performed to determine the position of the internal mammary chain (IMC). Based on these results, a 5-field treatment technique was developed that would include the breast, supraclavicular fossa, and ipsilateral IMC, while maintaining a low dose to the heart, lungs, and contralateral breast. This technique was implemented in a cohort of 13 patients. RESULTS: The lateral position of the right and left IMC were measured in three cephalo-caudad positions: at the clavicular heads, upper manubrium, and midsternum (at the 2nd/3rd rib interspace). The mean lateral separation between the right and left IMC chains at each level (and 95% confidence interval) at each level were 5.8 cm (4.67-7.00), 5.6 cm (4.49-6.73), and 5.9 cm (4.66-7.19), respectively. Treatment was delivered to 13 patients using a 5-field technique, with tangential photon fields for the breast, anterior and posterior supraclavicular/axillary field, and a matching anterior electron field. Three-dimensional treatment planning of a representative case confirmed adequate coverage of the planning target volume (PTV). The median dose to the whole heart was 10 Gy, and 20% of the ipsilateral lung received more than 20 Gy. Seven of the 13 patients treated experienced moist desquamation at the junction of the electron field and breast tangents, and 1 patient had persistent ulceration at 3 months' follow-up. CONCLUSION: The 5-field technique described in this paper provides good coverage to the breast and regional nodes with acceptable toxicity, and without requiring three-dimensional treatment planning or intensity-modulated radiotherapy techniques.