Opportunities in Cancer Nanotechnology: A Conversation with NCI’s Dr. Piotr Grodzinski

NCI recently released the Cancer Nanotechnology Plan 2015. In this interview, Piotr Grodzinski, Ph.D., director of NCI's Office of Cancer Nanotechnology Research, discusses the 2015 plan as well as new developments in nanotechnology-based therapeutics and diagnostics and the clinical opportunities being generated by the nanotechnology field.

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Building a Hit List For the Fight Against Metastatic Castration Resistant Prostate Cancer.

Building a Hit List For the Fight Against Metastatic Castration Resistant Prostate Cancer.

Cancer Biol Ther. 2016 Jan 29;:0

Authors: Strope JD, Price DK, Figg WD

Abstract
Identification of genetic alterations in Metastatic Castration Resistant Prostate Cancer (mCRPC) may provide scientists and clinicians with a list of new targets for drug research and development. Recently published in Cell, Robinson et al. present the first look at genetic data from mCRPC lesions gathered over multiple years and from many institutions.

PMID: 26822877 [PubMed - as supplied by publisher]

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Building a Hit List For the Fight Against Metastatic Castration Resistant Prostate Cancer.

Building a Hit List For the Fight Against Metastatic Castration Resistant Prostate Cancer.

Cancer Biol Ther. 2016 Jan 29;:0

Authors: Strope JD, Price DK, Figg WD

Abstract
Identification of genetic alterations in Metastatic Castration Resistant Prostate Cancer (mCRPC) may provide scientists and clinicians with a list of new targets for drug research and development. Recently published in Cell, Robinson et al. present the first look at genetic data from mCRPC lesions gathered over multiple years and from many institutions.

PMID: 26822877 [PubMed - as supplied by publisher]

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Building a Hit List For the Fight Against Metastatic Castration Resistant Prostate Cancer.

Building a Hit List For the Fight Against Metastatic Castration Resistant Prostate Cancer.

Cancer Biol Ther. 2016 Jan 29;:0

Authors: Strope JD, Price DK, Figg WD

Abstract
Identification of genetic alterations in Metastatic Castration Resistant Prostate Cancer (mCRPC) may provide scientists and clinicians with a list of new targets for drug research and development. Recently published in Cell, Robinson et al. present the first look at genetic data from mCRPC lesions gathered over multiple years and from many institutions.

PMID: 26822877 [PubMed - as supplied by publisher]

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Screening and identification of proteins interacting with IL-24 by the yeast two-hybrid screen, Co-IP, and FRET assays.

Interleukin-24 (IL-24) is an ideal tumor-suppressor gene, but the mechanisms underlying its antitumor specificity remain to be elucidated. The best way to investigate these problems is to begin from the initiation of corresponding signaling cascades activated by IL-24 with screening and identifying those proteins that interacted with IL-24. With the aim of identifying these initial interactions, a yeast two-hybrid screening was performed by transforming AH109 cells containing PGBKT7-IL-24 with a liver cDNA plasmid library. These cells were then plated on synthetic nutrient medium (SD/-Trp/-Leu/-His) for the first screening and on quadruple dropout medium containing X-[alpha]-gal for the second screening. Positive colonies were further verified by repeating the MATE experiments, co-immunoprecipitation (Co-IP) analysis, and fluorescence resonance energy transfer (FRET) assays in vitro. Following the yeast two-hybrid screening, 15 genes were selected for sequencing, with two genes, HLA-C and NDUFA13, further verified using Co-IP assays and FRET assays. Both HLA-C and NDUFA13 were found to interact with IL-24. We found that HLA-C and NDUFA13 could interact with IL-24 and it may be involved in the signal induced by IL-24. Overall, this study contributes further insight into the cancer-specific apoptosis-inducing abilities of IL-24 to potentially enhance its therapeutic potential, and it also provides outlets for other biological functions of IL-24. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Radiotherapy Noncompliance and Clinical Outcomes in an Urban Academic Cancer Center

Publication date: Available online 30 January 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Nitin Ohri, Bruce D. Rapkin, Chandan Guha, Shalom Kalnicki, Madhur Garg
BackgroundPatient noncompliance with daily external beam radiotherapy (RT) is a prevalent issue in some patient populations. Here we examine associations between RT noncompliance and clinical outcomes.MethodsWe reviewed all patients who completed courses of external beam RT with curative intent in our department from the years 2007-2012 for cancers of the head and neck, breast, lung, cervix, uterus, or rectum. Patients who missed two or more scheduled RT appointments (excluding planned treatment breaks) were deemed noncompliant. Univariate, multivariable, and propensity-matched analyses were performed to examine associations between RT noncompliance and clinical outcomes.Results266/1,227 patients (21.7%) were noncompliant. With median follow-up of 50.9 months, 108 recurrences (8.8%) and 228 deaths (18.6%) occurred. In univariate analyses, RT noncompliance was associated with increased recurrence risk (5-year cumulative incidence 16% v. 7%, p<0.001), inferior recurrence-free survival (RFS, 5-year actuarial rate 63% v. 79%, p<0.001), and inferior overall survival (OS, 5-year actuarial rate 72% v. 83%, p<0.001). In multivariable analyses that were adjusted for disease site and stage, comorbidity score, gender, ethnicity, race, and socioeconomic status (SES), RT noncompliance was associated with inferior recurrence, RFS, and OS rates. Propensity score matched models yielded results nearly identical to those seen in univariate analyses. Low SES was associated with RT noncompliance and was associated with inferior clinical outcomes in univariate analyses, but SES was not associated with inferior outcomes in multivariable models.ConclusionFor cancer patients being treated with curative intent, RT noncompliance is associated with inferior clinical outcomes. The magnitudes of these effects demonstrate that RT noncompliance can serve as a behavioral biomarker to identify high-risk patients who require additional interventions. Treatment compliance may mediate the associations that have observed linking SES and clinical outcomes.

Teaser

Patient noncompliance with daily external beam radiotherapy (RT) is a prevalent issue in some patient populations. The present analysis demonstrates that, in a large cohort of patients who were treated with curative intent, RT noncompliance was associated with increased risk of disease recurrence and death. The magnitudes of these effects demonstrate that RT noncompliance may serve as a behavioral biomarker to identify high-risk patients who require additional interventions to achieve optimal outcomes.


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Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer

Publication date: Available online 29 January 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jonathan L. Muldermans, Lindsay B. Romak, Eugene D. Kwon, Sean S. Park, Kenneth R. Olivier
Purpose/Objective(s)To review outcomes of patients with oligometastatic prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT) and to identify variables associated with local failure.Methods and MaterialsWe retrospectively reviewed records of patients treated with SBRT for oligometastatic PCa. Metastasis control (i.e. control of the treated lesion, MC), biochemical progression-free survival (BPFS), distant progression-free survival (DPFS), and overall survival (OS) were estimated with the Kaplan-Meier method.ResultsSixty-six men with 81 metastatic PCa lesions, 50 of which were castrate-resistant, were included in the analysis. Lesions were in bone (n=74), lymph nodes (n=6), or liver (n=1). SBRT was delivered in 1 fraction to 71 lesions (88%), at a median dose of 16 Gy (range, 16-24 Gy). The remaining lesions received 30 Gy in 3 fractions (n=6) or 50 Gy in 5 fractions (n=4). Median follow-up was 16 months (range, 3-49 months). Estimated MC at 2 years was 82%. BPFS, DPFS, and OS were 54%, 45%, and 83%, respectively. On multivariate analysis, only the dose of SBRT was significantly associated with MC; lesions treated with 16 Gy had 58% MC and those treated with ≥18 Gy had 95% MC at 2 years (P≤.001). At 2 years, MC for lesions treated with 18 Gy (n=21) was 88%. No patient treated with ≥18 Gy in a single fraction or with any multi-fraction regimen had local failure. Six patients (9%) had grade 1 pain flare, and 2 (3%) had grade 2 pain flare. No grade 2 or greater late toxicities were reported.ConclusionsSBRT for patients with oligometastatic prostate cancer provided optimal metastasis control and acceptable toxicity with doses ≥18 Gy. BPFS was 54% at 16 months with the inclusion of SBRT in the treatment regimen. SBRT should be considered in patients with castration-refractory, oligometastatic prostate cancer who have limited options for systemic therapy.

Teaser

Use of stereotactic body radiotherapy (SBRT) has been reported in the treatment of oligometastatic prostate cancer; however, the optimal dose fractionation has not been elucidated. This analysis indicates that single-fraction SBRT using 16 Gy is associated with poorer local control relative to single-fraction SBRT using ≥18 Gy or higher-dose, multi-fraction SBRT regimens. Toxicity was acceptable in this series.


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An analysis of plan robustness for oesophageal tumours: comparing volumetric modulated arctherapy plans and spot scanning proton planning

Publication date: Available online 30 January 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Samantha Warren, Mike Partridge, Alessandra Bolsi, Anthony J. Lomax, Chris Hurt, Thomas Crosby, Maria A. Hawkins
PurposePlanning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient are hampered by the non-equivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice, and also assess the robustness of each technique. This study therefore seeks to compare volumetric modulated arc therapy (VMAT) and single-field optimisation (SFO) spot scanning proton therapy plans created using with simultaneous integrated boost (SIB) for dose escalation in mid-oesophageal cancer, and to analyse the effect of set-up and range uncertainties on these plans.Methods and MaterialsFor 21 patients, SIB plans with a physical dose prescription of 2 Gy / 2.5 Gy per fraction (in 25 fractions) to PTV50Gy / PTV62.5Gy (primary tumour with 0.5cm margins) were created and evaluated for robustness to random set-up errors and proton range errors. Dose-volume metrics were compared for the optimal and uncertainty plans with p< 0.05 (Wilcoxon) taken as significant.ResultsSFO reduced mean lung dose by 51.4% (range: 35.1 – 76.1%) and mean heart dose by 40.9% (15.0 – 57.4%) compared to VMAT. Proton plan robustness to 3.5% range error was acceptable: across all patients CTV D98 was 95.0-100.4% of prescribed dose (PD) and GTV D98 was 98.8-101%. Set-up error robustness was patient anatomy dependant and potential minimum dose per fraction was always lower with SFO than VMAT: CTV D98 was lower by 0.6-7.8% PD and GTV D98 lower by 0.3 - 2.2% of prescribed GTV dose.ConclusionsSFO plans achieve significant sparing of normal tissue compared to VMAT for mid-oesophageal cancer. Target dose coverage in SIB proton plans was less robust to random set-up errors, and may be unacceptable for certain patients. Robust optimisation to ensure adequate target coverage of SIB proton plans may be beneficial.

Teaser

Comparing spot-scanning proton therapy single-field optimisation plans (SFO) with arctherapy (VMAT) plans indicates that SFO can achieve significant sparing of normal tissue for mid-oesophageal cancer compared to VMAT. However, the boost volume dose coverage in SIB proton plans appears less robust to set-up errors. Robust optimisation to ensure adequate target coverage of SIB proton plans may be beneficial.


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