The Value of Early Tumor Size Response to Chemotherapy in Pediatric Rhabdomyosarcoma

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood. Results of clinical trials, with three-year event-free and overall survival as primary outcomes, often take 7 to 10 years. Identification of an early surrogate biomarker, predictive for survival, is therefore crucial. We conducted a systematic review to define the prognostic value of early tumor size response in children with IRSG group III rhabdomyosarcoma. The search included MEDLINE/EMBASE from inception to 18 November 2020. In total, six studies were included, describing 2010 patients, and assessed by the Quality in Prognosis Studies (QUIPS) instrument. Four studies found no prognostic value for tumor size response, whereas two studies reported a prognostic effect. In these two studies, the survival rate of patients with progressive disease was not separately analyzed from patients with stable disease, potentially explaining the difference in study outcome. In conclusion, our findings support that early progression of disease is associated with poorer survival, justifying adaptation of therapy. However, in patients with non-progressive disease, there is no evidence that the degree of response is a prognostic marker for survival. Because the vast majority of patients do not have progressive disease, early tumor size response should be reconsidered for assessment of treatment efficacy. Therefore, at present, early surrogate biomarkers for survival are still lacking

Parotid Gland Stem Cell Sparing Radiation Therapy for Patients With Head and Neck Cancer:A Double-Blind Randomized Controlled Trial

BACKGROUND: Radiotherapy for head and neck cancer (HNC) frequently leads to salivary gland damage and subsequent xerostomia. The radiation response of parotid glands of rats, mice, and patients critically depends on dose to its stem cells, mainly located in the gland's main ducts (stem cell rich (SCR) region). Therefore, this double-blind randomized controlled trial aimed to test the hypothesis that parotid gland stem cell sparing radiotherapy preserves parotid gland function better than currently-used whole parotid gland sparing radiotherapy. METHODS: HNC patients (n=102) treated with definitive radiotherapy were randomized between standard parotid sparing and stem cell sparing (SCS) techniques. The primary endpoint was >75% reduction in parotid gland saliva production compared to pretreatment production (FLOW12M). Secondary endpoints were several aspects of xerostomia 12 months after treatment. RESULTS: Fifty-four patients were assigned to the standard arm and 48 to the SCS arm. Only dose to the SCR regions (contralateral 16 and 11 Gy (p=0.004) and ipsilateral 26 and 16 Gy (p=0.001), standard and SCS arm respectively) and pretreatment patient-rated daytime xerostomia (35% and 13% (p=0.01), standard and SCS arm respectively) differed significantly between the arms. In the SCS arm, 1 patient (2.8%) experienced FLOW12M compared to 2 (4.9%) in the standard arm (p=1.00). However, a trend towards better relative parotid gland salivary function in favor of SCS radiotherapy was shown. Moreover, multivariable analysis showed that mean contralateral SCR region dose was the strongest dosimetric predictor for moderate-to-severe patient-rated daytime xerostomia and grade ≥2 physician-rated xerostomia, the latter including complaints of alteration in diet. CONCLUSIONS: No significant better parotid function was observed in SCS radiotherapy. However, additional multivariable analysis showed that dose to the SCR region was more predictive for development of parotid gland function related xerostomia endpoints, than dose to the entire parotid gland

Impact of sarcopenia on survival and late toxicity in head and neck cancer patients treated with radiotherapy

Background and purpose: Sarcopenia is emerging as an adverse prognostic factor for survival and complication risk in cancer patients. This study aims to determine the impact of sarcopenia on survival and late toxicity in a large cohort of head and neck squamous cell carcinoma (HNSCC) patients treated with definitive (chemo)radiotherapy ((C)RT). Materials and methods: HNSCC patients treated with definitive (C)RT from January 2007 to June 2016 were included. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscles at level C3. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was evaluated using the Kaplan–Meier method. Multivariable association models were developed to assess the impact of sarcopenia on late toxicity. Results: The study population was composed of 750 HNSCC patients. Cut-off values for sarcopenia were set at SMI < 42.4 cm2/m2 (men) and <30.6 cm2/m2 (women) corresponding lowest gender specific quartile. Sarcopenic patients had significantly poorer survival rates, especially those with lower performance status and locally advanced disease. In oropharyngeal cancer patients, survival was more determined by p16 status than by sarcopenia. In multivariable analysis, sarcopenia was associated with worse OS (HR 0.72, p = 0.012) and DFS (HR 0.67, p = 0.001). In multivariable association models, sarcopenia was associated with physician-rated xerostomia six months after treatment (OR 1.65, p = 0.027) and physician-rated dysphagia six and twelve months after treatment (OR 2.02, p = 0.012 and 2.51, p = 0.003, respectively). Conclusion: Sarcopenia in HNSCC patients receiving definitive (C)RT is an independent prognostic factor for worse survival outcomes and is associated with physician-rated toxicity

Prevalence and prediction of trismus in patients with head and neck cancer:A cross-sectional study

BACKGROUND: Trismus occurs frequently in patients with head and neck cancer. Determining the prevalence and associated factors of trismus would enable prediction of the risk of trismus for future patients. METHODS: Based on maximal mouth opening measurements, we determined the prevalence of trismus in 730 patients with head and neck cancer. Associated factors for trismus were analyzed using univariate analyses and multivariate logistic regression analyses. Based on the regression model, a calculation tool to predict trismus was made. RESULTS: Prevalence of trismus was 23.6%. Factors associated with trismus were: advanced age; partial or full dentition; tumors located at the maxilla; mandible; cheek; major salivary glands; oropharynx; an unknown primary; a free soft tissue transfer after surgery; reirradiation; and chemotherapy. CONCLUSION: About one-fourth of patients with head and neck cancer develop trismus. Based on prevalence and associated factors of trismus, a simple calculation tool predicts the risk of trismus in these patients

Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group

PURPOSE: To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS: In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION: Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis

Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Introduction: Sentinel lymph node biopsy (SLNB) is important for staging in patients with primary cutaneous melanoma. Did having previously undergone SLNB also affect outcomes in patients once they have progressed to metastatic melanoma in the era prior to adjuvant therapy?Methods: Data were retrieved from the Dutch Melanoma Treatment Registry, a prospectively collected, nationwide database of patients with unresectable stage IIIC or IV (advanced) melanoma between 2012 and 2018. Melanoma-specific survival (MSS) was compared between patients with advanced cutaneous melanoma, previously treated with a wide local excision (WLE) or WLE combined with SLNB as initial treatment of their primary tumor. Cox regression analyses were used to analyze the influence of different variables on MSS.Results: In total, 2581 patients were included, of whom 1412 were treated with a WLE of the primary tumor alone and 1169 in whom this was combined with SLNB. At a median follow-up of 44 months from diagnosis of advanced melanoma, MSS was significantly longer in patients who had previously undergone SLNB {median 23 months (95% confidence interval [CI] 19–29) vs. 18 months (95% CI 15–20) for patients treated with WLE alone; p = 0.002}. However, multivariate Cox regression did not identify SLNB as an independent favorable prognostic factor for MSS after diagnosis of advanced melanoma.Conclusion: Prior to the availability of adjuvant systemic therapy, once patients have unresectable stage IIIC or IV (advanced) melanoma, there was no difference in disease outcome for patients who were or were not previously staged with SLNB.</p

Imaging findings in craniofacial childhood rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3–5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive COX-2. The response to meloxicam and irradiation (dose-range of 0–6 Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24–72 h exposure to 250–750 μM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to 750 μM meloxicam for 24 h increased the fraction of cells in the radiosensitive G2/M cell cycle phase in D384 (18–27%) and U251 (17–41%) cells. 750 μM meloxicam resulted in radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells