Palliative Care and Palliative Radiotherapy Education in Radiation Oncology: A Survey of US Radiation Oncology Program Directors

Publication date: Available online 1 December 2016
Source:Practical Radiation Oncology
Author(s): Randy L. Wei, Lauren E. Colbert, Joshua Jones, Margarita Racsa, Gabrielle Kane, Steve Lutz, Neha Vapiwala, Kavita Dharmarajan
Purpose/ObjectiveTo assess the state of palliative and supportive care (PSC) and palliative radiotherapy educational curricula in radiation oncology residency programs in the United States.Materials and methodsWe surveyed 87 program directors of radiation oncology residency programs in the United States from September 2015 to November 2015. An electronic survey on PSC and palliative radiotherapy education during residency was sent to all program directors. The survey consisted of questions on (1) perceived relevance of PSC and palliative radiotherapy to radiation oncology training, (2) formal didactic sessions on domains of PSC and palliative radiotherapy, (3) effective teaching formats for PSC and palliative radiotherapy education, (4) and perceived barriers for integrating PSC and palliative radiotherapy into the residency curriculum.ResultsA total of 57 responses (63%) were received. Most program directors agreed or strongly agreed that PSC (93%) and palliative radiotherapy (99%) are important competency for radiation oncology residents and fellows. However, 67% of residency programs had formal educational activities in principles and practice of PSC. Most programs had one or more hours of formal didactics on management of pain (67%), management of neuropathic pain (65%), and management of nausea and vomiting (63%). However, only 35%, 33%, and 30% had dedicated lectures on initial management of fatigue, assessing role of spirituality, and discussing advance care directives, respectively. Lastly, 85% of programs reported having a formal curriculum on palliative radiotherapy. Programs were most likely to have education on palliative radiation to brain, bone, and spine, but less likely on visceral, or skin metastasis.ConclusionResidency program directors believe that PSC and palliative radiotherapy are important competencies for their trainees and support increasing education in these two educational domains. Many residency programs have structured curricula on PSC and palliative radiation education, but room for improvement exists in management of fatigue, assessing role of spirituality and discussion regarding advance care planning.



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A Survey of Residents' Experience with Patient Safety and Quality Improvement Concepts in Radiation Oncology

Publication date: Available online 1 December 2016
Source:Practical Radiation Oncology
Author(s): Matthew B. Spraker, Matthew Nyflot, Kristi Hendrickson, Eric Ford, Gabrielle Kane, Jing Zeng




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Use of indocyanine green and the HyperEye system for detecting sentinel lymph nodes in breast cancer within a population of European patients: a pilot study

Abstract

Background

Certain studies suggest that using indocyanine green (ICG) could be comparable with using radioisotopes (RI) in detecting sentinel lymph nodes (SLNs) in breast cancer. A number of these studies were performed in Asia. The objective of our pilot study was to evaluate within a European population of breast cancer patients the detection rate of SLNs using ICG and the HyperEye system and the concordance in SLNs detected using this method and the standard method involving RI and a gamma probe.

Methods

Ten female patients with early-stage breast cancer (Czech Republic) indicated for partial mastectomy and SLN biopsy were subjected to standard application of RI. Before surgery, ICG was administered periareolarly in the amount of 1 ml of 0.5% solution. Sentinel lymph nodes were first detected perioperatively exclusively using ICG fluorescence and the HyperEye device (Mizuho, Japan). Only after removal of all SLNs found in this way was the standard hand-held gamma probe used to detect RI, and any potential additional SLNs not found with ICG were then extirpated.

Results

In all 10 cases, at least one SLN was successfully detected using ICG. Nevertheless, in five patients, 1–4 additional SLNs were found using the gamma probe. Complete concordance in detecting SLNs therefore occurred in only one half of the cases. Metastases in SLNs were found in a total of two cases. Had we used only ICG for detection, one of these two cases would have been incorrectly evaluated as N0 (ICG false negativity).

Conclusions

The study did not confirm the hypothesis that the use of ICG with the HyperEye system can currently be considered a method fully comparable with using RI and a gamma probe in a population of European patients. Although the detection rate is high, a significantly lower number of SLNs were detected using ICG than using RI (p = 0.03). Thus, there would be a higher probability for false negatives to occur in using SLN biopsy. This is caused mainly by the limited permeability of tissues to fluorescent radiation and the difficulty therefore of detecting nodes located deeper beneath the body's surface.

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Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the PPAR-{delta} Pathway

Peroxisome proliferator-activated receptor delta (PPAR-) is a nuclear receptor transcription factor that regulates gene expression during development and disease states, such as cancer. However, the precise role of PPAR- during tumorigenesis is not well understood. Recent data suggest that PPAR- may have context-specific oncogenic and tumor-suppressive roles depending on the tissue, cell-type, or diet-induced physiology in question. For example, in the intestine, pro-obesity diets, such as a high-fat diet (HFD), are associated with increased colorectal cancer incidence. Interestingly, many of the effects of an HFD in the stem and progenitor cell compartment are driven by a robust PPAR- program and contribute to the early steps of intestinal tumorigenesis. Importantly, the PPAR- pathway or its downstream mediators may serve as therapeutic intervention points or biomarkers in colon cancer that arise in patients who are obese. Although potent PPAR- agonists and antagonists exist, their clinical utility may be enhanced by uncovering how PPAR- mediates tumorigenesis in diverse tissues and cell types as well as in response to diet. Clin Cancer Res; 22(23); 5636–41. ©2016 AACR.

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Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA

Purpose: The expanding number of targeted therapeutics for non–small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS.

Experimental Design: A total of 112 plasma samples obtained from a consecutive study of 102 prospectively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue samples, when possible.

Results: We detected 275 alterations in 45 genes, and at least one alteration in the ctDNA for 86 of 102 patients (84%), with EGFR variants being most common. ctDNA NGS detected 50 driver and 12 resistance mutations, and mutations in 22 additional genes for which experimental therapies, including clinical trials, are available. Although ctDNA NGS was completed for 102 consecutive patients, tissue sequencing was only successful for 50 patients (49%). Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding concordance of 79%, with a shorter time interval between tissue and blood collection associated with increased concordance (P = 0.038). ctDNA sequencing identified eight patients harboring a resistance mutation who developed progressive disease while on targeted therapy, and for whom tissue sequencing was not possible.

Conclusions: Therapeutically targetable driver and resistance mutations can be detected by ctDNA NGS, even when tissue is unavailable, thus allowing more accurate diagnosis, improved patient management, and serial sampling to monitor disease progression and clonal evolution. Clin Cancer Res; 22(23); 5772–82. ©2016 AACR.

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Genomic Approaches to Understanding Response and Resistance to Immunotherapy

Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for patients with advanced cancers. However, such therapy has benefited only a subset of patients, with some patients failing to respond to treatment at all and others achieving a limited response followed by tumor progression. Understanding factors contributing to an effective response and further elucidating mechanisms of resistance will be crucial as these therapies are applied more broadly. Genomics-based approaches have significantly advanced the study of response and resistance to immunotherapy in general, and to immune checkpoint blockade more specifically. Here, we review how genomic and transcriptomic approaches have identified both somatic and germline positive correlates of response, including high mutational/neoantigen load and low intratumoral heterogeneity, among others. The genomic analysis of resistant tumors has additionally identified crucial factors involved in resistance to immune checkpoint blockade, including loss of PTEN and upregulation of other immune checkpoints. Overall, the continued use of genomic techniques at the point of care, combined with appropriate functional studies, would ideally lead to a better understanding of why certain patients respond to immune-based therapies, allowing clinicians to identify the subset of patients likely to benefit from such therapy, and potentially providing insight into how other therapies may be added in combination to increase the number of patients who may benefit from immunotherapy. Clin Cancer Res; 22(23); 5642–50. ©2016 AACR.

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PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo

Purpose: Great advances have recently been made in treating patients with metastatic melanoma. However, existing therapies are less effective on cerebral than extracerebral metastases. This highlights the potential role of the brain environment on tumor progression and drug resistance and underlines the need for "brain-specific" therapies. We previously showed that the PI3K-AKT survival pathway is hyperactivated in brain but not extracerebral melanoma metastases and that astrocyte-conditioned medium activates AKT in melanoma cells in vitro. We therefore tested the PI3K inhibitor buparlisib as an antitumor agent for melanoma brain metastases.

Experimental Design and Results: Buparlisib inhibited AKT activity, decreased proliferation, and induced apoptosis in metastatic melanoma cell lines and short-term brain melanoma cells, irrespective of their BRAF and NRAS mutation status. In addition, buparlisib inhibited hyperactivated AKT and induced apoptosis in melanoma cells that were stimulated with astrocyte-conditioned medium. The growth of tumors induced by injecting human BRAF- and NRAS-mutant metastatic melanoma cells into the brain of mice was significantly inhibited by buparlisib.

Conclusions: These results emphasize the value of targeting the PI3K pathway as a strategy to develop drugs for melanoma brain metastases. Clin Cancer Res; 22(23); 5818–28. ©2016 AACR.

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