The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer.

INTRODUCTION: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. MATERIALS AND METHODS: This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m2 (normal weight and reference), 25.0-29.9 kg/m2 (overweight) or ≥30.0 kg/m2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]. RESULTS: Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90). CONCLUSION: This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m2, and to verify calculated dosing of carboplatin for appropriateness.

Clinical relevance of cone beam computed tomography in mandibular third molar removal: A multicentre, randomised, controlled trial.

PURPOSE: The aims of this study were to investigate the effectiveness of cone beam computed tomography (CBCT) compared to panoramic radiography (PR), prior to mandibular third molar removal, in reducing patient morbidity, and to identify risk factors associated with inferior alveolar nerve (IAN) injury. MATERIAL AND METHODS: This multicentre, randomised, controlled trial was performed at three centres in the Netherlands. Adults with an increased risk for IAN injury, as diagnosed from PR, were included in the study. In one arm of the study, patients underwent an additional CBCT prior to third molar surgery. In a second arm of the study, no additional radiographs were acquired. The primary outcome measure was the number of patient-reported altered sensations 1 week after surgery. As secondary outcome measures, the number of patients with objective IAN injury, with long-term (>6 months) IAN injury, the occurrence of other postoperative complications, the Oral Health Related Quality of Life-14 (OHIP-14) questionnaire responses, postoperative pain (visual analogue scale score), duration of surgery, number of emergency visits, and number of missed days of work or study were scored. RESULTS: A total of 268 patients with 320 mandibular third molars were analysed according to the intention-to-treat principle. The overall incidence of IAN injury 1 week after surgery was 6.3%. No significant differences between CBCT and PR for temporary IAN injury (p = 0.64) and all other secondary outcomes were registered. A lingual position of the mandibular canal (MC) and narrowing, in which the diameter of the MC lumen was decreased at the contact area between the MC and the roots, were significant risk factors for temporary IAN injury. CONCLUSION: Although CBCT is a valuable diagnostic adjunct for identification of an increased risk for IAN injury, the use of CBCT does not translate into a reduction of IAN injury and other postoperative complications, after removal of the complete mandibular third molar. In these selected cases of a high risk for IAN injury, an alternative strategy, such as monitoring or a coronectomy, might be more appropriate. (http://clinicaltrials.gov, NCT02071030).

[Bisphosphonate-associated osteonecrosis of the jaws. 2. Six case reports]. / Bisfosfonaatgerelateerde osteonecrose van de kaak. 2. Zes casussen.

The diagnostic procedures and the treatment of 6 patients with bisphosphonate-related osteonecrosis of the jaw are reported. During recent years, bisphosphonates have been prescribed with increasing frequency. The main pharmacological effect is the inhibition of bone resorption, mediated by osteoclast activity impairment. The osteonecrosis is usually very therapy resistant and may cause considerable morbidity. Therefore, oral screening is indicated and focal oral infections should be eradicated prior to therapy with bisphosphonates. If bisphosphonate therapy has already been started, invasive oral procedures should be restricted to unavoidable treatment. When invasive treatment can not be avoided, the risk of osteonecrosis may be reduced by primary wound closure, antibiotic prophylaxis and adequate oral hygiene measures, supplemented by using a chlorhexidine mouthrinse. Cessation of smoking is recommended.

Tumour embolization of the Vx2 rabbit head and neck cancer model with Dextran hydrogel and Holmium-poly(L-lactic acid) microspheres: a radionuclide and histological pilot study.

INTRODUCTION: Intra-arterial embolization of unresectable malignant tumours with biodegradable microspheres is an effective way of selective anti-tumour therapy. Promising candidates are Dextran hydrogel (Dex) microspheres for chemo-embolization and Holmium-166 poly(L-lactic acid) (166HoPLA) microspheres for radio-embolization. This study was performed to investigate the distribution of intra-arterially injected microspheres both in vivo and histologically in order to establish an optimal size of particles for embolization of head and neck tumours. MATERIAL: Twenty rabbits with Vx2 auricular tumours were embolized via the caudal auricular artery with 4 different batches of microspheres: Radioactive (166)HoPLA microspheres sieved between 20 and 50 microm and Dextran hydrogel microspheres sieved between 20 and 100 microm (Dex20), 30 and 100 microm (Dex30) or 50 and 100 microm (Dex50). Dex20 and Dex50 microspheres were labelled with 99mTechnetium in six cases. METHODS: The average particle size of the microspheres was determined. The proportion of microspheres entrapped in the tumour was measured with a gamma camera. The distribution of microspheres around the primary tumour and spill of particles over into lungs or other organs was analysed from histological sections. RESULTS: The mean particle diameter varied from 19 to 66 microm: (166)HoPLA 19+/-11 microm, Dex20 40+/-19 microm, Dex30 50+/-19 microm, Dex50 66+/-21 microm. The 19 microm(166)HoPLA particles proved inadequate for embolization as 51% spilled over into the lungs, whereas over 95% of the 40-66 microm Dex microspheres were retained within the primary tumour area. Particle density in lung tissues proved significantly lower for the Dex50 group. Stray emboli to the brain occurred in two rabbits. CONCLUSION: The results of this investigation show that both Dextran hydrogel and holmium-166 poly(L-lactic acid) microspheres are potential candidates for embolization of head and neck cancer. In future studies, arterio-arteriolar anastomoses which might confound treatment should be identified and occluded. Particles with a number weighted mean diameter of at least 40 microm and a volume weighted mean size up to 70 microm should be used.