Radiotherapy in Oral Cancers: Current Perspective and Future Directions

Oral cancers form one of the most common malignancies seen worldwide, with a steady increase in number over time. Surgery with the addition of adjuvant therapy forms the cornerstone of therapeutic management for these cancers. Despite excellent surgical management, loco-regional recurrences have always been of concern. This has expanded the role of radiotherapy, with concomitant therapies, allowing to establish an effective management protocol. Over the last two decades, there have been huge strides taken towards understanding these specific aspects and providing insight into the most fruitful application of radiotherapy in these patients. In this chapter, we have presented the oncologists perspective to dealing with the non-surgical aspects of oral cancer management. We have elaborated on the chronological order with which radiotherapy has evolved and provided the contemporary aspects of decision making, essential for current practice. The evidence-based approach will address all components of radiotherapy workflow from basic understanding of patient’s anatomy, planning & evaluation during therapy to the outcomes & toxicity profiles to be expected in day-to-day clinics. Established guidelines have been incorporated into the graphical representations to ensure scenario-based understanding. Future perspectives, essential for identifying the possible direction of therapy & potential improvements in outcomes, have also been addressed

Phase II trial of palbociclib in patients with metastatic urothelial cancer after failure of first-line chemotherapy

Background: The majority of urothelial cancers (UC) harbor alterations in retinoblastoma (Rb) pathway genes that can lead to loss of Rb tumour suppressor function. Palbociclib is an oral, selective inhibitor of CDK 4/6 that restores Rb function and promotes cell cycle arrest. Methods: In this phase II trial, patients with metastatic platinum-refractory UC molecularly selected for p16 loss and intact Rb by tumour immunohistochemistry received palbociclib 125 mg p.o. daily for 21 days of a 28-day cycle. Primary endpoint was progression-free survival at 4 months (PFS4) using a Simon’s two-stage design. Next-generation sequencing including Rb pathway alterations was conducted. Results: Twelve patients were enrolled and two patients (17%) achieved PFS4 with insufficient activity to advance to stage 2. No responses were seen. Median PFS was 1.9 months (95% CI 1.8–3.7 months) and median overall survival was 6.3 months (95% CI 2.2–12.6 months). Fifty-eight percent of patients had grade ≥3 hematologic toxicity. There were no CDKN2A alterations found and no correlation of Rb pathway alterations with clinical outcome. Conclusions: Palbociclib did not demonstrate meaningful activity in selected patients with platinum-refractory metastatic UC. Further development of palbociclib should only be considered with improved integral biomarker selection or in rational combination with other therapies

International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

The Khorana Score in Predicting Venous Thromboembolism for Patients with Metastatic Urothelial Carcinoma and Variant Histology Treated with Chemotherapy

Background: The Khorana score is a predictive risk model for venous thromboembolism (VTE) in patients with cancer planning to receive chemotherapy. Urothelial carcinoma and variant histologies (UC/VH) were underrepresented in the model. We sought to evaluate whether the Khorana score predicts for VTE in a retrospective multinational data set of patients with metastatic UC/VH. Methods: Patients diagnosed with metastatic UC/VH who received chemotherapy were eligible. Those with incomplete or miscoded data were excluded. Khorana scores were calculated based on the pretreatment data and categorized into high (≥3) or intermediate (1-2) VTE risk. Other patient-, tumor-, and therapy-related factors were also analyzed. The ‡2 and logistic regression analyses were used to assess differences in VTE rates based on the clinical characteristics. Subgroup analyses were performed to evaluate the Khorana score and associated variables for early (<3 months) and late (>3 months) VTE. Results: A total of 943 patients were eligible for analysis. The cumulative VTE rate was 9.9%. There was no statistical difference in overall VTE rate between Khorana high- and intermediate-risk groups (P =.16). In the multivariate analysis, nonurothelial histology (odds ratio [OR] = 2.56; P =.002) and the presence of cardiovascular disease (CVD) or CVD risk factors (OR = 2.14; P =.002) were associated with increased VTE risk. In the first 3 months from initiation of chemotherapy, Khorana high risk (OR = 2.08; P =.04) was associated with higher VTE rates. White blood cell (WBC) count (OR = 1.05; P =.04) was the only significant Khorana variable for early VTE. Conclusions: The Khorana score stratifies early but not overall VTE risk in patients with metastatic UC/VH. The WBC count drives the increased early VTE risk seen with the Khorana score. © SAGE Publications

Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer

Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05). These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease