Ludi E. Smeele

Functional outcomes and rehabilitation strategies in patients treated with chemoradiotherapy for advanced head and neck cancer: a systematic review

Organ preservation with radiotherapy and concomitant chemotherapy has become an accepted treatment modality in advanced head and neck cancer. Unfortunately, organ preservation is not synonymous with function preservation. The aim of this review was to systematically assess the effects of the disease and chemoradiotherapy (CRT) on functions such as swallowing, mouth opening, nutrition, pain and quality of life in patients with head and neck cancer. Another aim was to search for (evidence-based) techniques or strategies known to alleviate or rehabilitate the loss of function(s) associated with CRT. Two databases were searched (time period, January 1997 to August 2007) for the terms head and neck cancer, chemotherapy or cisplatin and radiotherapy, and the functional outcomes swallowing, trismus, nutrition, pain and quality of life or a variation of those words. In total, 15 relevant articles were identified that met the inclusion criteria. The majority of the studies that met the criteria focused on the outcomes swallowing, quality of life, and nutrition. Two studies reported on the outcome pain, but no paper reported on the outcome trismus. Only two papers mentioned rehabilitation options, but specific information was lacking. Further long-term prospective research is essential, not only to determine the function impairment caused by the tumor and CRT, but also to assess the effects of known and newly developed rehabilitation measures. Therefore, in September 2006, the Netherlands Cancer Institute started a randomised clinical trial (RCT): Prevention of trismus, swallowing and speech problems in patients treated with chemoradiotherapy for advanced head and neck cancer. This systematic review was carried out to collect the baseline information for the future outcomes of this RCT.

Novel insights into pathological changes in muscular arteries of radiotherapy patients.

BACKGROUND AND PURPOSE Vascular disease is increased after radiotherapy and is an important determinant of late treatment-induced morbidity and excess mortality. This study evaluates the nature of underlying pathologic changes occurring in medium-sized muscular arteries following irradiation. MATERIALS AND METHODS Biopsies of irradiated medium-sized arteries and unirradiated control arteries were taken from 147 patients undergoing reconstructive surgery with a vascularised free flap following treatment for head and neck (H&N) or breast cancer (BC). Relative intimal thickening was derived from the ratio of the thickness of the intima to the thickness of the media (IMR) on histological sections. Proteoglycan, collagen and inflammatory cell content were also scored. RESULTS Intimal thickness was significantly increased in irradiated vessels: in the H&N group the IMR was 1.5-fold greater without correction for the control artery (p=0.018); in the BC group the IMR increased 1.4-fold after correction for the control artery (p=0.056) at a mean of 4 years following irradiation. There was an increase in the proteoglycan content of the intima of the irradiated IMA vessels, from 65% to 73% (p=0.024). Inflammatory cell content was increased in the intima of the irradiated H&N vessels (p=0.014). CONCLUSIONS Radiation-induced vascular pathology differs quantitatively and qualitatively from age-related atherosclerosis.

Dysphagia and trismus after concomitant chemo-Intensity-Modulated Radiation Therapy (chemo-IMRT) in advanced head and neck cancer; dose-effect relationships for swallowing and mastication structures

BACKGROUND AND PURPOSE Prospective assessment of dysphagia and trismus in chemo-IMRT head and neck cancer patients in relation to dose-parameters of structures involved in swallowing and mastication. MATERIAL AND METHODS Assessment of 55 patients before, 10-weeks (N=49) and 1-year post-treatment (N=37). Calculation of dose-volume parameters for swallowing (inferior (IC), middle (MC), and superior constrictors (SC)), and mastication structures (e.g. masseter). Investigation of relationships between dose-parameters and endpoints for swallowing problems (videofluoroscopy-based laryngeal Penetration-Aspiration Scale (PAS), and study-specific structured questionnaire) and limited mouth-opening (measurements and questionnaire), taking into account baseline scores. RESULTS At 10-weeks, volume of IC receiving ≥60 Gy (V60) and mean dose IC were significant predictors for PAS. One-year post-treatment, reported problems with swallowing solids were significantly related to masseter dose-parameters (mean, V20, V40 and V60) and an inverse relationship (lower dose related to a higher probability) was observed for V60 of the IC. Dose-parameters of masseter and pterygoid muscles were significant predictors of trismus at 10-weeks (mean, V20, and V40). At 1-year, dose-parameters of all mastication structures were strong predictors for subjective mouth-opening problems (mean, max, V20, V40, and V60). CONCLUSIONS Dose-effect relationships exist for dysphagia and trismus. Therefore treatment plans should be optimized to avoid these side effects.

The association of treatment delay and prognosis in head and neck squamous cell carcinoma (HNSCC) patients in a Dutch comprehensive cancer center

OBJECTIVE The increasing volume of head and neck squamous cell carcinoma (HNSCC) patients can lead to longer intervals between histopathological diagnosis and primary treatment. This could cause psychological distress to the patient, but more importantly could possibly lead to tumor progression and decreased survival. Accordingly, this study investigates these relationships. METHODS The correlation of professional delay and clinical characteristics of 2493 patients, treated between 1990 and 2011 with oral, oropharyngeal, hypopharyngeal and laryngeal SCC, was investigated. Patients were divided in two groups based on treatment delay, defined as the interval between histopathological diagnosis and initial treatment. Univariate and multivariate proportional hazards models were used to assess disease specific survival (DSS) and disease free survival (DFS). RESULTS Year of diagnosis, tumor site and therapy were significantly related to treatment delay. Tumor stage was not related to treatment delay. Multivariate regression models revealed that the group with a delay of more than 30 days had a better DSS (HR .838, CI .697-.922, p=.041) and DFS (HR .816, CI .702-.947), p=.007) than the group treated within 30 days. CONCLUSION In our study, treatment delay up to 90 days is not related to impaired survival. This argument can be used extremely cautiously to comfort patients who have to wait several weeks for treatment. Although, possible tumor progression during treatment delay could have led to increased morbidity subsequent to more extensive treatment. Also, possible negative psychological impact of delay in treatment should not be underestimated.

Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly : A prospective randomized study in squamous cell head and neck cancer

The main objective of this study was to investigate whether nondaily intravenous administration of amifostine was as effective as daily intravenous administration with regard to the reduction of the incidence of Grade 2 or greater xerostomia in patients with head and neck cancer.

Ultrasound-guided aspiration cytology for the assessment of the clinically N0 neck: Factors influencing its accuracy†

Ultrasound‐guided fine‐needle aspiration cytology (US‐FNAC) can be used to diminish the risk of missing occult metastases and for early detection during follow‐up.

Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment

BACKGROUND Radiotherapy is a well-known cause of adverse events (AEs). To reduce AEs, an innovative local treatment was developed in Amsterdam: Ablative surgery, MOuld brachytherapy and surgical REconstruction (AMORE). AIMS (1) to determine the prevalence of AEs in HNRMS survivors and (2) to compare AEs between survivors treated with the international standard: external beam radiotherapy (EBRT-based: London) and survivors treated with AMORE if feasible, otherwise EBRT (AMORE-based: Amsterdam). METHODS All HNRMS survivors, treated in London or Amsterdam between January 1990 and December 2010 (n = 153), and alive ⩾ 2 years post-treatment were eligible (n = 113). A predefined list of AEs was assessed in a multidisciplinary clinic and graded according to the Common Terminology Criteria for Adverse Events. RESULTS Eighty HNRMS survivors attended the clinic (median follow-up 10.5 years); 63% experienced ⩾ 1 severe or disabling event, and 76% had ⩾ 5 AEs (any grade). Survivors with EBRT-based treatment were, after adjustment for site, age at diagnosis, and follow-up duration, at increased risk to develop any grade 3/4 event or ⩾ 5 AEs (any grade) compared with survivors with AMORE-based treatments (p = 0.032 and 0.01, respectively). Five year overall survival (source population) after EBRT-based treatment was 75.0%, after AMORE-based treatment 76.9%, p = 0.56. CONCLUSION This study may serve as a baseline inventory and can be used in future studies for prospective assessments of AEs following the introduction of novel local treatment modalities. AMORE-based local treatment resulted in similar overall survival and a reduction of AEs secondary to local treatment.

CLOSURE OF TRACHEOESOPHAGEAL FISTULA WITH PREFABRICATED REVASCULARIZED BILAMINAR RADIAL FOREARM FREE FLAP

Tracheoesophageal fistula (TEF) is a rare but serious complication associated with high mortality rates. Traditional management of TEF includes primary closure with or without interposition of regional tissue flaps but is associated with a significant recurrence risk, especially in case of larger fistulas. Application of microvascular free flap reconstruction is an emerging alternative in the surgical management of large TEFs, but may be limited by issues of flap bulkiness and requirement for neoepithelialization across the large inner flap surface.

Treatment of myogenic temporomandibular disorder: a prospective randomized clinical trial, comparing a mechanical stretching device (TheraBite®) with standard physical therapy exercise

Abstract Aims: To compare in a randomized controlled clinical trial (RCT) the application of the TheraBite® (TB) Jaw Motion Rehabilitation System with a standard physical therapy (PT) exercise regimen for the treatment of myogenic temporomandibular disorder (TMD). Methodology: Myogenic TMD patients were randomized for the use of the TB device or for standard PT. Mandibular function was assessed with the mandibular function impairment questionnaire (MFIQ). Pain was evaluated using a visual analog scale, and maximum inter-incisor (mouth) opening (MIO) was measured using the disposable TB range of motion scale. Results: Of the 96 patients randomized (46 TB, 50 standard PT exercises), 38 actually started with the TB device and 41 with the standard PT exercises. After six-week follow-up, patients using the TB device reported a significantly greater functional improvement (MFIQ score) than the patients receiving regular PT exercises (P = 0·0050). At 6 weeks, no significant differences in pain, and active or passive MIO were found between the two groups. At 3 months, patients in both treatment groups did equally well, and showed a significant improvement in all parameters assessed. Conclusions: This RCT on myogenic TMD treatment, comparing standard PT with passive jaw mobilization using the TheraBite Jaw Motion Rehabilitation System®, shows that both treatment modalities are equally effective in relieving myogenic TMD symptoms, but that the use of the TB device has the benefit of achieving a significantly greater functional improvement within the first week of treatment.

An epidemiological evaluation of salivary gland cancer in the Netherlands (1989-2010).

BACKGROUND The relative 5-year survival rate of salivary gland cancer is moderate at best. This study was set up to evaluate whether the improvements in diagnosis and treatment in the last decades impacted the incidence, mortality and survival of salivary gland cancer. METHODS Data on patients with salivary gland cancer from 1989 through 2010 were extracted from the Netherlands Cancer Registry (NCR); we examined incidence, mortality and relative survival. Furthermore, information on sex, age, tumor stage, histology, and treatment was taken into account. RESULTS A total of 2737 patients were included. Fifty-three percent (53%) were males and 47% were females with a significant higher proportion of early stages in women. In 2010, the incidence rate (European Standardized Rate (ESR)) of salivary gland cancer was 0.9 per 100,000 per year. The estimated annual percentage change in incidence rate since 1989 equaled 0.6% (95%CI: -0.2-1.4). Mortality rates (ESR) decreased in men until 1997 and increased thereafter. Mortality in women remained stable at 1.5 per 100,000. Over time more patients were treated by surgery and radiotherapy (p<0.001). The relative five-year survival rate equaled 69% and did not change in time. CONCLUSION We observed no relevant changes in incidence or mortality rates in the last two decades. Despite the increased combined treatment by surgery and radiotherapy, survival did not improve. This implies an urgent need for the development of new effective treatment modalities.