Demographic, clinical and lifestyle-related correlates of accelerometer assessed physical activity and fitness in newly diagnosed patients with head and neck cancer.

Introduction: Objective measurements of levels of physical activity and fitness in patients with head and neck cancer (HNC) are lacking. Furthermore, demographic, clinical and lifestyle-related correlates of low levels of physical activity and fitness in patients with HNC are unknown. This study aims to investigate the levels of accelerometer that assessed physical activity and fitness in patients with HNC and to identify their demographical, clinical and lifestyle-related correlates.Methods: Two hundred and fifty-four patients who were recently diagnosed with HNC and participated in the NETherlands QUality of life and Biomedical cohort studies In head and neck Cancer (NET-QUBIC) study were included. Physical activity (accelerometer), cardiorespiratory fitness (Chester Step Test), hand grip strength (hand dynamometer) and lower body muscle function (30-second chair-stand test) were assessed. Multivariable linear regression analyses with a stepwise forward selection procedure were used.Results: Patients spent 229 min/d in physical activity of which 18 min/d in moderate-to-vigorous physical activity. The mean predicted VO2max was 27.9 ml/kg/min, the mean hand grip strength was 38.1 kg and the mean number of standings was 14.3. Patients with lower educational level, more comorbidity and higher tumor stage spent significantly less time in physical activity. Older patients, females and patients with a higher tumor stage had significantly lower cardiorespiratory fitness levels. Older patients, females, patients with more comorbidity, patients with normal weight and patients who have never smoked had significantly lower hand grip strength. Older patients, patients with lower educational level, smokers and patients with more comorbidity had a significantly lower function of lower body muscle.Conclusions: Pre-treatment levels of physical activity, cardiorespiratory fitness and lower body muscle function are low in patients with HNC. Based on this study, exercise programs targeted and tailored to patients with low levels of physical activity and fitness can be developed.

Correction to: Advancing interdisciplinary research in head and neck cancer through a multicenter longitudinal prospective cohort study: the NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) data warehouse and biobank.

Following publication of the original article [1], the authors reported the name of R.J. Baatenburg de Jong was incorrectly tagged in the HTML version of the article.

Advancing interdisciplinary research in head and neck cancer through a multicenter longitudinal prospective cohort study: the NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) data warehouse and biobank.

BACKGROUND: Worldwide, over 500,000 people are diagnosed with head and neck cancer each year, a disease with major impact on life expectancy and quality of life. The purpose of the Netherlands Quality of life and Biomedical Cohort study (NET-QUBIC) is to advance interdisciplinary research that aims to optimize diagnosis, treatment, and supportive care for head and neck cancer patients and their informal caregivers. METHODS: Using an extensive assessment protocol (electronic clinical record form, patient reported outcome measures and fieldwork (interviews and physical tests)), clinical data and data on quality of life, demographic and personal factors, psychosocial (depression, anxiety, fatigue, pain, sleep, mental adjustment to cancer, posttraumatic stress), physical (speech, swallowing, oral function, malnutrition, physical fitness, neurocognitive function, sexual function), lifestyle (physical activity, nutrition, smoking, alcohol, drugs), and social factors (social function, social support, work, health care use, and costs) are collected and stored in the data warehouse. A longitudinal biobank is built with tumor tissue, blood and blood components, saliva samples, and oral rinses. An infrastructure for fieldwork and laboratory protocols is established at all participating centers. All patients fill out patient reported outcome measures before treatment and at 3, 6, 12, 24, 36, 48, and 60 months follow-up. The interviews, physical tests and biological sample collection are at baseline and 6, 12, and 24 months follow-up. The protocol for caregivers includes blood sampling and oral rinses at baseline and a tailored list of questionnaires, administered at the same time points as the patients. In total, 739 HNC patients and 262 informal caregivers have been included in 5 out of the 8 HNC centers in the Netherlands. DISCUSSION: By granting access to researchers to the NET-QUBIC data warehouse and biobank, we enable new research lines in clinical (e.g. treatment optimization in elderly patients), biological (e.g. liquid biopsy analysis for relapse detection), health related quality of life (e.g. the impact of toxicity on quality of life), and interrelated research (e.g. health related quality of life in relation to biomarkers and survival).

Importance of tumor volume in supraglottic and glottic laryngeal carcinoma.

PURPOSE: The aim of our study was to assess the prognostic value of tumor volume compared to and in addition to T-stage on local control (LC), disease-free survival (DFS), and overall survival (OS) in glottic and supraglottic laryngeal carcinoma patients. PATIENTS AND METHODS: In 150 patients, we determined tumor volume on diagnostic CT scans. We applied crude and multivariable Cox regression analysis to relate volume (continuous), T-stage and the combination to 5-year DFS, OS, and LC. Before, we examined the linearity assumption of the association between volume and outcome with restricted cubic spline functions. Prognostic performance of the models was examined by determination of the model's discrimination. Discriminative ability was determined with the C statistic referring to the ability to discriminate between patients who do and do not develop an event during follow-up. RESULTS: A strong association between tumor volume and DFS and OS was found. The restricted cubic spline plot did not indicate a non-linear relationship between tumor volume and DFS and local control. Tumor volume demonstrated a better discriminative ability to predict DFS and OS compared to T-stage (0.68 and 0.57 vs. 0.59 and 0.54, respectively). For local control, T-stage showed a higher discriminative ability than tumor volume (0.63 vs. 0.61). The combined model increased discriminative power (0.69). CONCLUSION: Volume seems to be more important than T-stage in prediction of DFS or OS in laryngeal squamous cell carcinoma patients. Perhaps prediction of DFS, OS, and LC could be improved by including tumor volume into the staging process.

Impaired Geriatric 8 Score is Associated with Worse Survival after Radiotherapy in Older Patients with Cancer.

AIMS: To investigate whether the Geriatric 8 (G8) score and the Timed Get Up and Go Test (TGUGT), together with clinical and demographic patient characteristics, are associated with survival and late toxicity after (chemo)radiation therapy, administered with curative intent in older patients with cancer. MATERIALS AND METHODS: Four hundred and two patients aged ≥65 years (median age 72 years, range 65-96 years), diagnosed with either breast, non-small cell lung, prostate, head and neck, rectal or oesophageal cancer, and referred for curative (chemo)radiation therapy, took part in a multicentre prospective cohort study in eight radiotherapy centres in the Netherlands. The G8 and TGUGT scores were assessed before starting treatment. Other potential predictors and late toxicity were also recorded. Survival status and date of death, if applicable, were ascertained at the Dutch national death registry. RESULTS: After 2.5 years, the overall survival was 83%. Survival was 87% for patients with high G8 scores and 55% for patients with low G8 scores (Log-rank P value < 0.0001). Survival was 77% for patients with good TGUGT results and 50% for patients with poor TGUGT results (Log-rank P value < 0.001). In multivariable analysis, in addition to age and type of primary tumour, the association of the G8 score with overall survival remained, with a hazard ratio of 2.1 (95% confidence interval 1.2-3.8) for low versus high scores. CONCLUSIONS: G8 was associated with overall survival in older patients with cancer irradiated with curative intent. This association was independent of the predictive value of age and primary tumour.

MR-guidance in clinical reality: current treatment challenges and future perspectives.

Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites.MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment.

[Saliva and intensity modulated radiotherapy]. / Speeksel en intensiteitsgemoduleerde radiotherapie.

A dry mouth (xerostomia) is a serious side effect for head and neck cancer patients treated with radiotherapy. The degree of xerostomia is dependent on the dosage in the parotid glands. New, advanced radiation techniques, such as intensity-modulated radiotherapy, can reduce the dosage in the parotid glands, resulting in a significant improvement in the functioning of these glands by comparison with conventional radiation techniques.

Variation in head and neck cancer care in the Netherlands: A retrospective cohort evaluation of incidence, treatment and outcome.

BACKGROUND: To explore variation in numbers and treatment between hospitals that treat head and neck cancer (HNC) in the Netherlands. MATERIAL AND METHODS: Patient, tumor and treatment characteristics were collected from the Netherlands Cancer Registry, while histopathological features were obtained by linkage to the national pathology record register PALGA. Inter-hospital variation in volume, stage, treatment, pathologically confirmed loco-regional recurrence and overall survival rate was evaluated by tumor site. RESULTS: In total, 2094 newly diagnosed patients were included, ranging from 65 to 417 patients in participating hospitals treating HNC in 2008. Oral cavity cancer was mainly treated by surgery only, ranging from 46 to 82% per hospital, while the proportion of surgery with (chemo)radiotherapy ranged from 18 to 40%. Increasing age, male sex, and high stage were associated with a higher hazard of dying. In oropharynx cancer, the use of (chemo)radiotherapy varied from 31 to 82% between hospitals. We found an indication that higher volume was associated with a lower overall hazard of dying for the total group, but not by subsite. Low numbers, e.g. for salivary gland, nasopharynx, nasal cavity and paranasal sinus, did not permit all desired analyses. CONCLUSION: This study revealed significant interhospital variation in numbers and treatment of especially oropharyngeal and oral cavity cancer. This study is limited because we had to rely on data recorded in the past for a different purpose. To understand whether this variation is unwanted, future research should be based on prospectively collected data, including detailed information on recurrences, additional case-mix information and cause of death.

Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.

PURPOSE: This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were randomly assigned to 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated. RESULTS: Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients. CONCLUSION: The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.

Bilateral temporal lobe necrosis after radiotherapy: confounding SPECT results.

A patient with seizures and a contrast-enhancing temporal lesion after radiation therapy for a chondrosarcoma of the nasal septum is described. To differentiate between radiation necrosis and recurrent tumor, thallium-201 (201Tl) SPECT was used. 201Tl SPECT revealed high local accumulation suggesting tumor growth; however, pathologic examination demonstrated focal necrosis with reactive changes but without tumor. The 201Tl SPECT findings in this patient demonstrate a possible diagnostic pitfall in differentiating recurrent tumor from radiation necrosis.

Radiotherapy in epithelial tumors of the parotid gland: case presentation and literature review.

A group of 113 patients irradiated for parotid tumor was studied retrospectively. Sixty-two patients were irradiated after superficial parotidectomy or enucleation of a pleomorphic adenoma. None of them had a recurrence after 5-15 years. Sixteen patients were irradiated postoperatively after surgery for a recurrence of pleomorphic adenoma. Only one of them had developed a recurrent tumor. Thirty-five patients with a malignant parotid tumor were treated by irradiation, 22 after surgery and 13 after biopsy only. Patients with a low malignancy tumor (10/11) and adenoid cystic carcinoma (6/12) responded better than patients with a high malignancy carcinoma (2/12). A tumor larger than 4 cm, facial nerve palsy, lymph node metastasis, and inoperability indicate a poor prognosis. With high dose radiotherapy it is possible to treat inoperable tumors successfully. Adenoid cystic carcinomas can respond well to irradiation alone.

Radiotherapy in T1 laryngeal cancer: prognostic factors for locoregional control and survival, uni- and multivariate analysis.

From 1975 through 1985, 194 patients with T1 glottic, 37 patients with T1 supraglottic, and 3 patients with T1 subglottic cancer were treated with radiotherapy. Local control and ultimate locoregional control (after salvage surgery) was 91% and 97% for T1 glottic, 84% and 81% for T1 supraglottic, and 2/3 and 3/3, respectively for subglottic tumors. In uni- and multivariate analysis local control for glottic tumors was associated with extension of the tumor on the vocal cord (entire length of vocal cord vs others, p = 0.01) and continuation of smoking after therapy (yes/no, p = 0.03). No prognostic factor for local control was found in supraglottic tumors. However, regional control and survival were impaired by N stage (N0 vs N+, p less than 0.0005), local recurrence (yes/no, p less than 0.0005), and extension of the tumor (one supraglottic subsite vs more than one, p less than 0.05). Mild late complications were seen in 13% of patients without salvage therapy. Following univariate analysis, field size, fraction size (greater than 2 Gy), maximum tumor dose (greater than 70 Gy), age, post-treatment biopsy, and tumor site were associated with complication rate. Following multivariate analysis, site, fraction size, maximum tumor dose, and continuation of smoking after therapy were independent prognostic factors for mild late complications (mostly arytenoid edema).

Regression after 50 Gy as a selection for therapy in advanced laryngeal cancer.

Radiation alone for advanced laryngeal cancer will result in an initial local control rate of 50%. When a local recurrence is diagnosed, only 50% will be successfully salvaged by surgery. To identify patients with a high chance of local control with radiation alone in advanced laryngeal cancer, the clinical response following radiotherapy was assessed a few days after 50 Gy/5 weeks. In patients with T-stage reduction or greater than 50% tumor regression radiotherapy was continued, if not, laryngectomy was performed after 4-6 weeks. According to this protocol 30 patients (out of 50) with T3/T4 laryngeal cancer were treated. Initial local control was assessed 6 weeks after radiotherapy, the ultimate local control included successful salvage surgery. Initial local control in patients, treated with a full course of radiotherapy after T-stage reduction or greater than 50% tumor regression, was 69% for T3 and 43% for T4 while the ultimate local control rate was 85% and 71% respectively. Although the percentage of voice preservation in our study was slightly lower (40%) than data from literature with radiation alone, the ultimate local control was high and comparable with those of combined therapy (in which laryngectomy is a part). The corrected actuarial 5-year survival in all T3 and T4 patients treated with radiation alone and salvage surgery was 73% and 31% respectively and was not different compared to surgery with pre- or post-operative radiotherapy, 74% and 53% respectively. We believe that this protocol may select a favorable group of patients for high dose radiation alone in T3 and probably in T4 laryngeal cancer.

Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region.

PURPOSE: To study the radiation tolerance of the parotid glands as a function of dose and volume irradiated. METHODS AND MATERIALS: One hundred eight patients treated with primary or postoperative radiotherapy for various malignancies in the head-and-neck region were prospectively evaluated. Stimulated parotid flow rate was measured before radiotherapy and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from CT-based treatment planning. The normal tissue complication probability model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow rate <25% of the preradiotherapy flow rate. RESULTS: The mean stimulated preradiotherapy flow rate of 174 parotid glands was 0.34 mL/min. The mean flow rate reduced to 0.12 mL/min 6 weeks postradiotherapy, but recovered to a mean flow rate of 0.20 mL/min at 1 year after radiotherapy. Reduction in postradiotherapy flow rate correlated significantly with mean parotid dose. No threshold dose was found. Increasing the irradiated volume of parotid glands from 0%-40% to 90-100% in patients with a mean parotid dose of 35-45 Gy resulted in a decrease in flow ratio from, respectively, approximately 100% to less than 10% 6 weeks after radiation. The flow ratio of the 90%-100% group partially recovered to 15% at 6 months and to 30% at 1 year after radiotherapy. The normal tissue complication probability model parameter TD(50) (the dose to the whole organ leading to a complication probability of 50%) was found to be 31, 35, and 39 Gy at 6 weeks, 6 months, and 1 year postradiotherapy, respectively. The volume dependency parameter n was around 1, which means that the mean parotid dose correlates best with the observed complications. There was no steep dose-response curve (m = 0.45 at 1 year postradiotherapy). CONCLUSIONS: This study on dose/volume/parotid gland function relationships revealed a linear correlation between postradiotherapy flow ratio and parotid gland dose and a strong volume dependency. No threshold dose was found. Recovery of parotid gland function was shown at 6 months and 1 year after radiotherapy. In radiation planning, attempts should be made to achieve a mean parotid gland dose at least below 39 Gy (leading to a complication probability of 50%).

Local control in T3 laryngeal cancer treated with radical radiotherapy, time dose relationship: the concept of nominal standard dose and linear quadratic model.

In a retrospective study of the Dutch cooperative head and neck group 104 evaluable patients with T3NxMO squamous cell carcinoma of the larynx were treated primarily with a full course of radiotherapy. The results of treatment are presented in terms of locoregional control. The actuarial 3-year local control rate was 53%. Regional control was 77% for node positive patients and 96% for N0 patients (p = 0.01). Surgical salvage was successful in 53% of cases with a local recurrence and in 3/8 regional recurrences, resulting in an ultimate locoregional control rate of 83% for N0 patients and 68% for N+ patients. A uni- and multivariate analysis of local control rate versus total dose, nominal standard dose, and extrapolated response dose has been done. To calculate extrapolated response dose the linear quadratic equation was used, assuming an a/b of 10 and a potential doubling time of clonogenic cells of 3, 5, and 7 days. In multivariate analysis the extrapolated response dose with a potential doubling time of 5 days was the only independent prognostic factor for local control (p = 0.069) and ultimate locoregional control (p = 0.0015). Nominal standard dose showed no dose-response relationship. Based on the S-shaped dose response curve, using the LQ model, several therapeutical options are discussed.

Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: radiation dose dependency and compensatory mechanisms.

PURPOSE: To study the ability of a prophylactic pilocarpine administration to preserve the rat parotid gland function after unilateral irradiation with graded doses of X-rays. METHODS: The right parotid gland of male albino Wistar rats was irradiated with single doses of X-rays (10-30 Gy, at 1.5 Gy min(-1)). Pilocarpine (4 mg/kg) was administered intraperitoneally, 1 hour prior to irradiation. Saliva samples of both left and right parotid gland were collected by means of miniaturized Lashley cups 4 days before and 3, 7, 10, and 30 days after irradiation. The parotid salivary flow rate (microl/min) was used as a parameter for the assessment of parotid gland function. RESULTS: Our data confirm that a single prophylactic treatment of pilocarpine can attenuate radiation-induced loss of gland function. Surprisingly, the effect of pilocarpine was not restricted to the irradiated gland only. Pilocarpine also enhanced the flow rate in the contralateral, nonirradiated gland. The latter effect was found for all doses above 10 Gy and became apparent around 7 days after the radiation treatment. The effectiveness of pilocarpine to attenuate function loss in the irradiated gland decreased with increasing dose and was lost after single doses of 30 Gy. CONCLUSIONS: Our data provide direct evidence that increasing the compensatory potential of the nondamaged gland, at least in part, underlies the "radioprotective effect" of pilocarpine in case of unilateral radiation. The ability of pilocarpine to ameliorate the early radiation-induced impairment of the parotid gland function in the irradiated gland may therefore be dependent on the remaining number of functional cells, and thus on the volume of the gland that lies within the radiation portal.

Fluorine-18-FDG detection of laryngeal cancer postradiotherapy using dual-head coincidence imaging.

UNLABELLED: The aim of this study was to investigate whether, in patients treated for laryngeal carcinoma, a differentiation was possible between local recurrence or local control using a dual-head SPECT camera with PET capability. METHODS: Eleven male patients (age range 51-71 yr; mean age 62 yr) who had previously undergone radiotherapy for laryngeal carcinoma were studied using 5 mCi (185 MBq) 18F-fluorodeoxyglucose (FDG). The mean interval between initial treatment and 18F-FDG PET was 21.9 mo (range 6-65 mo). Six patients had histologically proven local recurrence and five patients showed local control clinically. The mean follow-up in the local control group was 5.2 mo. RESULTS: Fluorine-18-FDG PET scans were positive in all six local relapses. Histopathological examination of the laryngectomy specimen revealed a mean tumor size of 2.6 cm (range 1.4-5.0 cm). In one patient, false-positive uptake was seen in an inflammatory lymph node. Fluorine-18-FDG PET scans were negative in all five patients with local control. CONCLUSION: It is possible to differentiate between local recurrence and local control in patients previously treated for laryngeal carcinoma with a dual-head SPECT scanner with PET capability.

CT-based parotid gland location: implications for preservation of parotid function.

PURPOSE: The position of the parotid gland in relation to surrounding structures was investigated. MATERIALS AND METHODS: Sixty-five patients with head and neck tumours were prospectively evaluated. Parotid position was determined using beam's eye views of CT images projected on simulator films. Distances between the different borders of the parotid gland and surrounding bony marks were quantitatively assessed. RESULTS: The parotid gland volume ranged from 12.9 to 46.4 cm(3). The distance between the cranial border of the parotid gland and the tuberculum anterior of the atlas ranged between 0.7 and 4.8 cm. The position of the parotid gland was unaffected by the angle of the mandible. CONCLUSIONS: The size and position of the parotid gland varies largely among patients. As the extent of radiation-induced salivary dysfunction depends on the volume of the gland tissue exposed, CT-based simulation of radiation fields is necessary.

The importance of vocal cord mobility in T2 laryngeal cancer.

In a retrospective study 75 patients with T2 laryngeal cancer treated from 1981 through 1985 were analysed. Of this group 71 patients had a full course of radiotherapy as primary therapy. All 71 patients were given 70 Gy/7 weeks on the primary and 50 Gy/5 weeks on the neck, 2 Gy per fraction. Various prognostic factors for local control and survival were studied. In our patient group we found vocal cord mobility to be an important prognostic factor for ultimate local control and survival. Patients with impaired cord mobility had a significantly worse ultimate local control (76%) than patients with normal cord mobility (98%) and a significantly worse corrected actuarial survival. It is concluded that impaired cord mobility means more advanced disease. Future studies will have to answer the question how to improve the local control rate in patients with impaired cord mobility, for example, by incorporating laryngectomy earlier in the treatment program of those patients who can not be cured by radiotherapy alone or by using innovative radiotherapy protocols.