Real-life assessment of Volumetric Modulated Arc Therapy (VMAT) toxicity in Head and Neck Squamous Cell Carcinoma (HNSCC) treatment

Conclusion: The present study demonstrates the feasibility of VMAT in association with platin or cetuximab in HNSCC and reports VMAT-related acute and late toxicities for the first time. Objectives: New radiotherapy techniques, such as Volumetric Modulated Arc Therapy (VMAT) were developed to lower RT-related toxicity. The aim of the present study was to investigate acute and late toxicities of head and neck squamous cell carcinoma (HNSCC) patients treated using VMAT. Methods: This study investigated retrospectively all patients with HNSCC who received VMAT in curative intent. Results: From 2010–2013, 150 patients were treated. Seventy-five patients (50%) received concurrent chemotherapy with VMAT, 51 patients (34%) received VMAT alone and 24 patients (16%) received concurrent cetuximab with VMAT. Mean delivered dose to planning target volume tumor (PTV T), high risk nodes (PTV HNR), low risk nodes (PTV LNR) and prophylactic nodes (PTV PN) were: 65.2 Gy, 62.9 Gy, 55.4 Gy, and 51.5 Gy, respectively. PTV mean coverages were higher than 96.5%. Most common grade 3/4 acute infield toxicities were mucosis (n?=?28, 19%), dysphagia (n?=?24, 16%), and dermatitis (n?=?24, 16%). With a median follow-up of 16.0 months, most common late toxicities were dysphagia (n?=?30, 20%), xerostomia (n?=?28, 19%), larynx stiff (n?=?17, 11%), and skin fibrosis (n?=?14, 9%).     

Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful?

Objective

To assess the effect of neoadjuvant targeted molecular therapies (TMTs) on size and level of inferior vena cava tumor thrombi and to evaluate their impact on surgical management.

Methods

We retrospectively analyzed the data of 14 patients treated for a clear cell renal cell carcinoma with inferior vena cava thrombi by neoadjuvant TMT before nephrectomy. Clinical, pathological and perioperative data were gathered retrospectively at each institution. The primitive tumor size and the thrombus size were defined by computed tomography before TMT. The tumor thrombus level was defined according to the Novick’s classification.

Results

Before TMT, thrombus level was staged I for 1 (7 %), II for 10 (72 %) and III (21 %) for 3 patients. First-line therapy was sunitinib in 11 cases and sorafenib in 3 cases. Median therapy duration was two cycles (1–5). Three patients experienced major adverse effects (grade III) during TMT. Following TMT, 6 (43 %) patients had a measurable decrease, 6 (43 %) had no change, and 2 (14 %) had an increase in the thrombus. One patient (7 %) had a downstage of thrombus level, 12 (85 %) had stable thrombi, and 1 (7 %) had an upstage. Regarding primary tumor, 7 (50 %), 5 (36 %) and 2 (14 %) patients had a decrease, stabilization and an increase in tumor size, respectively.

Conclusion

Neoadjuvant TMT appears to have limited effects on renal tumor thrombi. This retrospective study failed to demonstrate a significant impact of neoadjuvant TMT on surgical management of clear cell renal cell carcinoma with inferior vena cava tumor thrombi.     

Effect of body mass index on the outcomes of patients with upper and lower urinary tract cancers treated by radical surgery: Results from a Canadian multicenter collaboration

ObjectiveTo evaluate the effect of body mass index (BMI) on the outcomes of patients with urinary tract carcinoma treated with radical surgery.Materials and methodsData were collected from 10 Canadian centers on patients who underwent radical cystectomy (RC) (1998–2008) or radical nephroureterectomy (RNU) (1990–2010). Various parameters among subsets of patients (BMI<25, 25≤BMI<30, and BMI≥30 kg/m²) were analyzed. Kaplan-Meier and multivariate analyses were performed to assess the effect of BMI on overall survival, disease-specific survival, and recurrence-free survival (RFS).ResultsAmong the 847 RC and 664 RNU patients, there was no difference in histology, stage, grade, and margin status among the 3 patient subsets undergoing either surgery. However, RC patients with lower BMIs (<25 kg/m²) were significantly older (P = 0.004), had more nodal metastasis (P = 0.03), and trended toward higher stage (P = 0.052). RNU patients with lower BMIs (<25 kg/m²) were significantly older (P = 0.0004) and fewer received adjuvant chemotherapy (P = 0.04) compared with those with BMI≥30 kg/m²; however, there was no difference in tumor location (P = 0.20), stage (P = 0.48), and management of distal ureter among the groups (P = 0.30). On multivariate analysis, BMI was not prognostic for overall survival, disease-specific survival, and RFS in the RC group. However, BMI≥30 kg/m² was associated with more bladder cancer recurrences and worse RFS in the RNU group (HR = 1.588; 95% CI: 1.148–2.196; P = 0.0052).ConclusionsIncreased BMI did not influence survival among RC patients. BMI≥30 kg/m² is associated with worse bladder cancer recurrences among RNU patients; whether this is related to difficulty in obtaining adequate bladder cuff in patients with obesity requires further evaluation.     

Hypercalcemia is associated with a poor prognosis in lymphoma a retrospective monocentric matched-control study and extensive review of published reported cases

Annals of Hematology - The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that...     

Medical literature and vena cava filters: so far so weak

STUDY OBJECTIVE: With the development of percutaneous inferior vena cava (IVC) filters, IVC interruption has become a widely used procedure in patients with or at risk for venous thromboembolism. In an attempt at clarifying the indications for filter placement, a systematic literature review was undertaken. DESIGN: Bibliographic search and analysis. MEASUREMENTS AND RESULTS: A systematic MEDLINE search about vena cava filters produced a total of 568 references with abstracts between 1975 and 2000 inclusively. Each reference was analyzed according to predetermined criteria. Nearly two thirds (65.0%) of these publications were retrospective studies or case reports (33.3 and 31.7%, respectively), 12.9% were animal or in vitro studies, 7.4% were prospective studies, 6.7% were reviews, and 8.1% reported on miscellaneous related topics. Among the prospective studies, only 16 studies included > or = 100 patients, only 1 study was a randomized controlled trial (0.02% of 568 references), and heterogeneity among series precluded any relevant comparison. In a similar search about heparin and venous thromboembolism, 47.4% of 531 references were randomized controlled trials. CONCLUSIONS: Until more relevant data become available, literature reviews about vena cava filters will remain narrative, and many if not most indications for filter placement will remain a matter of opinion.     

Sinusoidal endothelial cell and hepatocyte death following cold ischemia-warm reperfusion of the rat liver

Cold ischemia-warm reperfusion (CI-WR) injury of the liver is characterized by marked alterations of sinusoidal endothelial cells (SECs), whereas hepatocytes appear to be relatively unscathed. However, the time course and mechanism of cell death remain controversial: early versus late phenomenon, necrosis versus apoptosis? We describe the occurrence and nature of cell death after different periods of CI with University of Wisconsin (UW) solution and after different periods of WR in the isolated perfused rat liver model. After 24- and 42-hour CI (viable and nonviable livers, respectively), similar patterns of liver cell death were seen: SEC necrosis appeared early after WR (10 minutes) and remained stable for up to 120 minutes. After 30 minutes of WR, apoptosis increased progressively with WR length. Based on morphological criteria, apoptotic cells were mainly hepatocytes within liver plates or extruded in the sinusoidal lumen. In addition, only after 42-hour CI were large clusters of necrotic hepatocytes found in areas of congested sinusoids. In these same livers, the hepatic microcirculation, evaluated by means of the multiple-indicator dilution technique, revealed extracellular matrix disappearance with no-flow areas. In conclusion, different time courses and mechanisms of cell death occur in rat livers after CI-WR, with early SEC necrosis followed by delayed hepatocyte apoptosis. These processes do not appear to be of major importance in the mechanism of graft failure because they are similar under both nonlethal and lethal conditions; this is not the case for the loss of the extracellular matrix found only under lethal conditions and associated with hepatocyte necrosis.