Cancers, Vol. 9, Pages 135: Can Intensity-Modulated-Radiotherapy Reduce Toxicity in Head and Neck Squamous Cell Carcinoma?

Cancers, Vol. 9, Pages 135: Can Intensity-Modulated-Radiotherapy Reduce Toxicity in Head and Neck Squamous Cell Carcinoma?

Cancers doi: 10.3390/cancers9100135

Authors: Julie van der Veen Sandra Nuyts

Intensity modulated radiotherapy (IMRT) is a modern radiotherapy technique that was implemented in the mid-1990s. It allows closer shaping of dose, to target volumes, thereby sparing organs at risk (OARs). Before the IMRT-era, two-dimensional radiotherapy (2DRT) and later three-dimensional conformal radiotherapy (3DCRT) were the techniques of choice, but this robust way of irradiating caused more normal tissue to receive a higher dose. Radiation of cancers in the head and neck region is complex because of close proximity to critical normal tissue and the large target volumes that need to be treated at high doses. IMRT offers an elegant solution compared with 3DCRT and surgery because it allows organ preservation and improved function preservation. In this manuscript, we review the rationales for IMRT, with an emphasis on toxicity outcomes compared with 3DCRT. We performed a review of the literature and looked at the most important randomised controlled trials comparing IMRT with 3DCRT. We conclude that IMRT is safe in regard to disease outcome, and that it allows better sparing of normal tissue, thereby causing less toxicity, resulting in a smaller impact on quality of life compared with conventional radiotherapy in the treatment of head and neck cancer.

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A revision of the Tokuhashi revised score improves the prognostic ability in patients with metastatic spinal cord compression

Abstract

Purpose

The Tokuhashi revised score from 2005 (TR2005) is the most recommended prognostic scoring system in patients with metastatic spinal cord compression (MSCC). However, recent studies have questioned its prognostic ability and the need for a new revision has been proposed. We aimed to assess whether a revision of the TR2005 can improve the prognostic ability of the scoring system.

Methods

In 2011 and 2012, a total of 1143 consecutive patients admitted with MSCC were prospectively included in a 2011 and a 2012 cohort. For the patients admitted in 2011 (n = 544), the components of the TR2005 including primary cancer diagnosis were analyzed regarding the prognostic ability. Based on these findings, a revision of the TR2005 score was defined as the Tokuhashi revised score 2017 (TR2017). The prognostic abilities of the TR2005 and the TR2017 were compared by Kaplan Meyer (KM) curves, and receiver-operating characteristics' (ROC) analysis was compared in a cohort of patients admitted in 2012 (n = 599).

Results

KM curves and ROC analysis showed that the TR2017 had better prognostic ability compared to the TR2005. The ROC areas were as follows: <6-months survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for ≥6-month survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for ≥12-month survival TR2017 = 0.72 and TR2005 = 0.67, and p = 0.0015.

Conclusions

The TR2017 can improve the prognostic ability of the TR2005 in patients with MSCC. This could affect the preoperative evaluation of patients suffering from MSCC.

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Monosomy 17 in potentially curable HER2 -amplified breast cancer: prognostic and predictive impact

Abstract

Purpose

HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I–III breast cancers with m17 and characterized the impact of trastuzumab treatment.

Methods

From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0.

Results

Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0–1+) were HER2 amplified by FISH.

Conclusions

In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.

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Unexpected hypotension in catecholamine reversal: a case report

Catecholamine agents are commonly used to support circulation; however, they may cause unexpected hypotension in a special situation. Here we describe the first unexpected case of hypotension in response to ca...

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Anthropometric factors and cutaneous melanoma: Prospective data from the population-based Janus Cohort

Abstract

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking status. During a mean follow-up of 27 years, 3000 incident CM cases were identified. In men, CM risk was positively associated with body mass index, body surface area (BSA), height and weight (all P_trends < 0.001), and the exposure-response curves indicated an exponential increase in risk for all anthropometric factors. Weight loss of more than 2 kg in men was associated with a 53% lower risk (HR 0.47, 95% CI: 0.39, 0.57). In women, CM risk increased with increasing BSA (P_trend = 0.002) and height (P_trend < 0.001). The shape of the height-CM risk curve indicated an exponential increase. Our study suggests that large body size, in general, is a CM risk factor in men, and is the first to report that weight loss may reduce the risk of CM among men. This article is protected by copyright. All rights reserved.

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How many cancer cases and deaths are potentially preventable? Estimates for Australia in 2013

Abstract

Cancer is a leading cause of disease burden in Australia, particularly fatal burden, accounting for an estimated thirty percent of deaths. Many cancers develop because of exposure to lifestyle and environmental factors that are potentially modifiable. We aimed to quantify the proportions and numbers of cancer deaths and cases in Australia in 2013 attributable to 20 modifiable factors in eight broad groupings that are established causes of cancer, namely: tobacco smoke (smoking and second-hand), dietary factors (low intake of fruit, non-starchy vegetables and dietary fibre; and high intake of red and processed meat), overweight/obesity, alcohol, physical inactivity, solar ultraviolet radiation, infections (seven agents), and reproductive factors (lack of breastfeeding, menopausal hormone therapy use, combined oral contraceptive use). We estimated population attributable fractions (PAF) using standard formulae incorporating exposure prevalence and relative risk data. Of all cancer deaths in Australia in 2013, approximately 38% overall (males 41%, females 34%) could be attributed to the factors assessed; the corresponding PAF for cancer cases was 33% (males 34%, females 32%). Tobacco smoke was the leading cause of cancer deaths and cases, with PAFs of 23% and 13% respectively, followed by dietary factors (5% deaths/5% cases), overweight/obesity (5%/4%) and infections (5%/3%). Cancer sites with the highest numbers of potentially preventable deaths/cases were lung (n=6,776/9,272), colorectum (n=1,974/7,380) and cutaneous melanoma (n=1,390/7,918). We estimate that about 16,700 cancer deaths and 41,200 cancer cases could be prevented in Australia each year if people's exposures to 20 causal factors were aligned with levels recommended to minimise cancer risk. This article is protected by copyright. All rights reserved.

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Role of Stem Cell Derived Exosomes In Tumor Biology

Abstract

Exosomes are nano-scale messengers loaded with bio-molecular cargo of RNA, DNA, and Proteins. As a master regulator of cellular signalling, stem cell (both normal, and cancer stem cells) secreted exosome orchestrate various autocrine and paracrine functions which alter tumor micro-environment, growth and progression. Exosomes secreted by one of the two important stem cell phenotypes in cancers a) Mesenchymal stem cells, and b) Cancer stem cells not only promote cancerous growth but also impart therapy resistance in cancer cells. In tumors, normal or mesenchymal stem cell (MSCs) derived exosomes (MSC-exo) modulate tumor hallmarks by delivering unique miRNA species to neighbouring cells and help in tumor progression. Apart from regulating tumor cell fate, MSC-exo are also capable of inducing physiological processes e.g. angiogenesis, metastasis etc. Similarly, cancer stem sells (CSCs) derived exosomes (CSC-exo) contain stemness-specific proteins, self-renewal promoting regulatory miRNAs, and survival factors. CSC-exo specific cargo maintains tumor heterogeneity and alters tumor progression. In this review we critically discuss the importance of stem cell specific exosomes in tumor cell signalling pathways with their role in tumor biology. This article is protected by copyright. All rights reserved.

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