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.

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).

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.

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.

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.

[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.

Guidelines in head and neck oncology compliance and consequences of deviations from the standard protocol for tongue and floor of mouth squamous carcinoma.

OBJECTIVES: To investigate the extent of violation of a regional guideline for the treatment of patients with carcinoma of the tongue/floor of mouth (ICD0 C02, C04). Different aspects of protocol violation (i.e. undertreatment or overtreatment) and consequences for treatment outcome were evaluated. DESIGN: Retrospective analysis of data from medical records. SETTING: The Department of Maxillofacial and Oral Surgery and the Department of Otorhinolaryngology and Head and Neck Surgery of the University Medical Centre Utrecht. PARTICIPANTS: A total of 217 patients treated between 1991 and 2001 for a stage II and stage III carcinoma of the tongue/floor of mouth. MAIN OUTCOME MEASURES: Protocol violation, tumour recurrence. RESULTS: The overall adherence to the guideline was 55%. In the non-adherence group of patients, 21% were overtreated, 71% were undertreated, and 8% were both overtreated and undertreated. There was no statistically significant difference in tumour recurrence between the two groups for stage II (P=0.68) or stage III (P=0.97) disease, or between undertreatment and overtreatment of patients with stage II (P=0.47) or stage III (P=0.90) disease. CONCLUSIONS: Although protocol violation occurs in as many as 45% of patients, this does not result in a worse tumour recurrence. Neither overtreatment nor undertreatment appears to affect the overall tumour recurrence.

Simultaneous radio- and chemotherapy for squamous cell carcinoma of the head and neck in daily clinical practice: 5 years experience in a University Hospital.

Several randomized studies and meta-analyses have shown that simultaneous radio- and chemotherapy prolongs survival in patients with unresectable squamous cell carcinoma of the head and neck as compared with conventional radiotherapy. We assessed the feasibility and effectiveness of simultaneous radiotherapy (35 x 2 Gy) and chemotherapy [cisplatinum 100 mg/m(2) or carboplatin (AUC 6) on days 1, 22 and 43] in daily clinical practice in a cohort of 87 patients treated at our institute between 1998 and 2002. Eighty patients completed radiotherapy according to schedule. Eighty patients received two courses of chemotherapy and 50 patients three courses. Nephrotoxity, bone marrow suppression and ototoxicity were the most frequent side-effects. Median weight loss was 8.5%. Median survival was 15 months and 44% of the patients were alive at 2 years. Patients receiving three courses of chemotherapy had a better survival than patients receiving two or less courses. Treatment with simultaneous radio- and chemotherapy for advanced head and neck cancer is a demanding, but feasible treatment in daily clinical practice. Survival seems to be comparable with the results achieved in patients selected for clinical trials.

Delayed radiation toxicity after focal or whole brain radiotherapy for low-grade glioma.

To evaluate the influence of radiation volume and other risk factors for the development of delayed radiation toxicity in patients treated for low-grade glioma, a retrospective analysis of 41 adult patients treated with focal or whole brain radiotherapy (WBRT) was performed. For all patients CT and MRI scans were revised to quantify brain atrophy and white matter lesions. Medical data were reviewed concerning baseline and tumor characteristics, treatment, survival, signs and symptoms of clinical encephalopathy and cardiovascular risk factors. In patients treated with WBRT an increased risk was found for brain atrophy (RR 3.1), white matter lesions (RR 3.8) and clinical encephalopathy (RR 4.2). An increased risk of atrophy (RR 2.2) and white matter lesions (RR 2.9) was also found in patients aged over 40 years. Furthermore, brain atrophy and white matter lesions were more severe in patients treated with WBRT and in older patients. In conclusion, both the incidence and the severity of abnormalities is greater in patients treated with WBRT and in older patients.

[Tumor growth during the waiting period for radiotherapy in patients with oropharyngeal carcinoma]. / Tumorgroei in de wachttijd voor radiotherapie bij patiënten met een orofarynxcarcinoom.

OBJECTIVE: To quantify the potential increase in tumour volume during the waiting time for radiotherapy in patients with oropharyngeal squamous cell carcinoma. DESIGN: Retrospective study. METHOD: The tumour volumes as assessed on the diagnostic CT scan and the planning CT scan were compared. Thirteen patients with oropharyngeal carcinoma were included in this study. Both their diagnostic CT scan (CT-1) and their planning CT scan (CT-2) were performed in the Utrecht university medical centre. Tumour volume was calculated by delineating the tumour on CT slices and multiplying the surface area by the inter-slice distance. Tumour volumes were delineated by three independent observers. Tumour growth during the waiting time was defined as the difference in tumour volume on CT-2 and CT-1, calculated as the average of three observations. RESULTS: The mean time between CT-1 and CT-2 was 33 days. The mean waiting period between the histopathological diagnosis and the start of radiotherapy was 56 days. Three groups could be distinguished: in one group the growth was less than 25% (n = 4), in one group the growth varied between 25 and 100% (n = 5), and in a third group there was growth of more than 100% (n = 4). Apart from this, in three cases the TNM stage had to be adjusted as a result of tumour progression. CONCLUSION: This study showed that the tumour volume increased by more than 50% during the waiting time for radiotherapy in 8 out of 13 patients with squamous cell carcinoma of the oropharynx.

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.

The influence of clinical factors on human stimulated parotid flow rate in cancer and other patients.

Reduced salivary secretion can produce a wide variety of complaints, having a negative impact on the daily life of a patient. Multiple causes of salivary hypofunction are described, however, there are no consistent data about the influence of clinical parameters on parotid gland function. We studied a group of patients with head and neck malignancies before treatment with radiotherapy. We used Lashley cups to collect stimulated parotid saliva simultaneously from both parotid glands. Sizes of the parotid gland, gender, age, tobacco and alcohol consumption, and tumour characteristics were related to the function of the parotid gland. A considerable variability in parotid output was found with a range of 0.03-1.66 ml/min (mean 0.34 ml/min). None of the variables were correlated with parotid flow. These results are important, especially when evaluating effects of radiation on parotid gland function.

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%).

White matter lesions and encephalopathy in patients treated for primary central nervous system lymphoma.

A retrospective analysis of the clinical presentations and neuroimaging characteristics of 33 patients with a primary central nervous system lymphoma (PCNL) who received cranial radiotherapy was performed to assess incidence of and risk factors for radiation-induced encephalopathy. CT and MRI scans were revised by a neurologist and a radiologist in conference. White matter abnormalities before and after radiotherapy on the last scan before recurrence were quantified according to a semi-quantitative scale. All available medical records were retrieved and reviewed with respect to demographic and tumor-related variables, treatment modalities, disease-free and overall survival and clinical symptoms and signs of encephalopathy. CT and MRI scans showed severe white matter lesions in 75% of 20 patients and in 86% of patients aged more than 60 years. Forty percent of patients presented with new clinical signs of cognitive impairment a median of 14.5 months after initial diagnosis (8.5 months after radiotherapy). The risk of white matter lesions appeared greater in patients aged >60 (RR 1.2, 95% CI = 0.8-2.0), in patients with prior white matter lesions (RR 1.3, 95% CI = 0.8-2.1) and in patients with multifocal cerebral lymphoma (RR 1.5, 95% CI = 1.0-2.1). In conclusion, the risk of white matter lesions and clinical symptoms and signs of encephalopathy is high in patients treated by radiotherapy for PCNL. The risk appears to be greatest in older patients, patients with multifocal tumor and in those with prior white matter lesions on CT or MRI.

F-18-fluoro-deoxy-glucose positron-emission tomography scanning in detection of local recurrence after radiotherapy for laryngeal/ pharyngeal cancer.

BACKGROUND: The objective of this investigation was to determine whether F18-fluoro-deoxy-glucose (FDG) positron-emission tomography (PET) could differentiate between local recurrence and late radiation effects after radiotherapy for laryngeal/pharyngeal cancer. METHODS: In a prospective study of 75 patients (67 larynx, eight oro/hypopharynx), 160 laryngoscopies and 109 FDG PET scans were performed on the head and neck region. The mean follow-up time after the first FDG PET scan was 23 months (minimum 1 year). RESULTS: Local recurrence was diagnosed in 37 patients: 19 after the first biopsy and 18 after follow-up biopsies. For all of the negative initial FDG scans (27), the biopsies that were taken at the same time were negative and no recurrence was seen for at least 1 year. The first FDG scan was a true positive in 34 of 48 patients. In 12 of the 14 patients with false-positive results, FDG scans were repeated; a decreased FDG uptake was found in 9 of the 12. The sensitivity and specificity of the first scan were respectively 92% and 63%; including subsequent FDG scans, the rates were 97% and 82%, respectively. CONCLUSIONS: When a local recurrence is suspected after radiotherapy for cancer of the larynx/pharynx, an FDG PET scan should be the first diagnostic step. No biopsy is needed if the scan is negative. If the scan is positive and the biopsy negative, a decreased FDG uptake measured in a follow-up scan indicates that a local recurrence is unlikely.