Introducing navigation during melanoma-related sentinel lymph node procedures in the head-and-neck region

Abstract

Background

Intraoperative sentinel node (SN) identification in patients with head-and-neck malignancies can be challenging due to unexpected drainage patterns and anatomical complexity. Here, intraoperative navigation-based guidance technologies may provide outcome. In this study, gamma camera-based freehandSPECT was evaluated in combination with the hybrid tracer ICG-^99mTc-nanocolloid.

Materials and methods

Eight patients with melanoma located in the head-and-neck area were included. Indocyanine green (ICG)-^99mTc-nanocolloid was injected preoperatively, whereafter lymphoscintigraphy and SPECT/CT imaging were performed in order to define the location of the SN(s). FreehandSPECT scans were generated in the operation room using a portable gamma camera. For lesion localization during surgery, freehandSPECT scans were projected in an augmented reality video-view that was used to spatially position a gamma-ray detection probe. Intraoperative fluorescence imaging was used to confirm the accuracy of the navigation-based approach and identify the exact location of the SNs.

Results

Preoperatively, 15 SNs were identified, of which 14 were identified using freehandSPECT. Navigation towards these nodes using the freehandSPECT approach was successful in 13 nodes. Fluorescence imaging provided optical confirmation of the navigation accuracy in all patients. In addition, fluorescence imaging allowed for the identification of (clustered) SNs that could not be identified based on navigation alone.

Conclusions

The use of gamma camera-based freehandSPECT aids intraoperative lesion identification and, with that, supports the transition from pre- to intraoperative imaging via augmented reality display and directional guidance.

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Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

BACKGROUND

The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)–positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies.

METHODS

The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared.

RESULTS

In total, 15,173 women (age range, 25-95 years; 7.1% were aged < 30 years) underwent both HPV and cytologic testing, and 1184 (8.4%) underwent biopsy. Cytology was positive in 19.4% of specimens, and HPV was positive in 14.5%. Eighty-four CIN-3–positive specimens were detected, including 55 that tested ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative.

CONCLUSIONS

There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3–positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be missed by primary HPV screening. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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The effect of resveratrol administration in irradiated mice on the induction of micronuclei in bone marrow

Abstract

Objective

Resveratrol (RSV) a medicinal polyphenol is synthesized by many plants in response to injury, infection, stress, and ultraviolet (UV) irradiation, present in the grapes, nuts, fruits, and wine.

Methods

In this study, we have investigated the antioxidant ability of RSV and its activity in the protection of radiation-induced DNA injury in X-radiated mice. The antioxidant strength of RSV was evaluated by the study of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging properties.

Results

Our results demonstrated that RSV shows strong antioxidant activity by this assay. When mice were exposed to 2 Gy X-radiation, there was an increase in the total MnPCE value and a decrease in the ratio [PCEs/ (PCEs + NCEs)] of bone marrow cells. RSV (50 mg/kg) pretreatment remarkably decreased the total MnPCE value and increased the ratio [PCEs/ (PCEs + NCEs)] in irradiated mice.

Conclusions

These results propose that RSV protects X-radiation-induced DNA damage in mice bone marrow cells, which may be related to its antioxidant activity.

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RNA-transfection of γ/δ T cells with a chimeric antigen receptor or an α/β T-cell receptor: a safer alternative to genetically engineered α/β T cells for the immunotherapy of melanoma

Abstract

Background

Adoptive T-cell therapy relying on conventional T cells transduced with T-cell receptors (TCRs) or chimeric antigen receptors (CARs) has caused substantial tumor regression in several clinical trials. However, genetically engineered T cells have been associated with serious side-effects due to off-target toxicities and massive cytokine release. To obviate these concerns, we established a protocol adaptable to GMP to expand and transiently transfect γ/δ T cells with mRNA.

Methods

PBMC from healthy donors were stimulated using zoledronic-acid or OKT3 to expand γ/δ T cells and bulk T cells, respectively. Additionally, CD8⁺ T cells and γ/δ T cells were MACS-isolated from PBMC and expanded with OKT3. Next, these four populations were electroporated with RNA encoding a gp100/HLA-A2-specific TCR or a CAR specific for MCSP. Thereafter, receptor expression, antigen-specific cytokine secretion, specific cytotoxicity, and killing of the endogenous γ/δ T cell-target Daudi were analyzed.

Results

Using zoledronic-acid in average 6 million of γ/δ T cells with a purity of 85% were generated from one million PBMC. MACS-isolation and OKT3-mediated expansion of γ/δ T cells yielded approximately ten times less cells. OKT3-expanded and CD8⁺ MACS-isolated conventional T cells behaved correspondingly similar. All employed T cells were efficiently transfected with the TCR or the CAR. Upon respective stimulation, γ/δ T cells produced IFNγ and TNF, but little IL-2 and the zoledronic-acid expanded T cells exceeded MACS-γ/δ T cells in antigen-specific cytokine secretion. While the cytokine production of γ/δ T cells was in general lower than that of conventional T cells, specific cytotoxicity against melanoma cell lines was similar. In contrast to OKT3-expanded and MACS-CD8⁺ T cells, mock-electroporated γ/δ T cells also lysed tumor cells reflecting the γ/δ T cell-intrinsic anti-tumor activity. After transfection, γ/δ T cells were still able to kill MHC-deficient Daudi cells.

Conclusion

We present a protocol adaptable to GMP for the expansion of γ/δ T cells and their subsequent RNA-transfection with tumor-specific TCRs or CARs. Given the transient receptor expression, the reduced cytokine release, and the equivalent cytotoxicity, these γ/δ T cells may represent a safer complementation to genetically engineered conventional T cells in the immunotherapy of melanoma (Exper Dermatol 26: 157, 2017, J Investig Dermatol 136: A173, 2016).

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Identification of cancer risk and associated behaviour: implications for social marketing campaigns for cancer prevention

Abstract

Background

Community misconception of what causes cancer is an important consideration when devising communication strategies around cancer prevention, while those initiating social marketing campaigns must decide whether to target the general population or to tailor messages for different audiences. This paper investigates the relationships between demographic characteristics, identification of selected cancer risk factors, and associated protective behaviours, to inform audience segmentation for cancer prevention social marketing.

Methods

Data for this cross-sectional study (n = 3301) are derived from Cancer Council New South Wales' 2013 Cancer Prevention Survey. Descriptive statistics and logistic regression models were used to investigate the relationship between respondent demographic characteristics and identification of each of seven cancer risk factors; demographic characteristics and practice of the seven 'protective' behaviours associated with the seven cancer risk factors; and identification of cancer risk factors and practising the associated protective behaviours, controlling for demographic characteristics.

Results

More than 90% of respondents across demographic groups identified sun exposure and smoking cigarettes as moderate or large cancer risk factors. Around 80% identified passive smoking as a moderate/large risk factor, and 40–60% identified being overweight or obese, drinking alcohol, not eating enough vegetables and not eating enough fruit. Women and older respondents were more likely to identify most cancer risk factors as moderate/large, and to practise associated protective behaviours. Education was correlated with identification of smoking as a moderate/large cancer risk factor, and with four of the seven protective behaviours. Location (metropolitan/regional) and country of birth (Australia/other) were weak predictors of identification and of protective behaviours. Identification of a cancer risk factor as moderate/large was a significant predictor for five out of seven associated cancer-protective behaviours, controlling for demographic characteristics.

Conclusions

These findings suggest a role for both audience segmentation and whole-of-population approaches in cancer-prevention social marketing campaigns. Targeted campaigns can address beliefs of younger people and men about cancer risk factors. Traditional population campaigns can enhance awareness of being overweight, alcohol consumption, and poor vegetable and fruit intake as cancer risk factors.

http://ift.tt/2v4Oyqp

Preventable and mitigable adverse events in cancer care: Measuring risk and harm across the continuum

BACKGROUND

Patient safety is a critical concern in clinical oncology, but the ability to measure adverse events (AEs) across cancer care is limited by a narrow focus on treatment-related toxicities. The objective of this study was to assess the nature and extent of AEs among cancer patients across inpatient and outpatient settings.

METHODS

This was a retrospective cohort study of 400 adult patients selected by stratified random sampling who had breast (n = 128), colorectal (n = 136), or lung cancer (n = 136) treated at a comprehensive cancer center in 2012. Candidate AEs, or injuries due to medical care, were identified by trained nurse reviewers over the course of 1 year from medical records and safety-reporting databases. Physicians determined the AE harm severity and the likelihood of preventability and harm mitigation.

RESULTS

The 400-patient sample represented 133,358 days of follow-up. Three hundred four AEs were identified for an overall rate of 2.3 events per 1000 patient days (91.2 per 1000 inpatient days and 0.9 per 1000 outpatient days). Thirty-four percent of the patients had 1 or more AEs (95% confidence interval, 29%-39%), and 16% of the patients had 1 or more preventable or mitigable AEs (95% confidence interval, 13%-20%). The AE rate for patients with breast cancer was lower than the rate for patients with colorectal or lung cancer (P ≤ .001). The preventable or mitigable AE rate was 0.9 per 1000 patient days. Six percent of AEs and 4% of preventable AEs resulted in serious harm. Examples included lymphedema, abscess, and renal failure.

CONCLUSIONS

A heavy burden of AEs, including preventable or mitigable events, has been identified. Future research should examine risk factors and improvement strategies for reducing their burden. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2wTak2z

A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma

BACKGROUND

Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity.

METHODS

This open-label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide. Patients in the Phase 2 Filanesib plus dexamethasone cohort (N = 55) had received prior alkylator therapy and had disease refractory to lenalidomide, bortezomib, and dexamethasone. Prophylactic filgrastim was incorporated during dose escalation and was used throughout Phase 2.

RESULTS

Patients in each cohort had received a median of ≥6 prior therapies. The most common dose-limiting toxicities were febrile neutropenia and mucosal inflammation. In Phase 2, Grade 3 and 4 cytopenias were reported in approximately 50% of patients. Nonhematologic toxicities were infrequent. Phase 2 response rates (partial responses or better) were 16% (single agent) and 15% (Filanesib plus dexamethasone). All responding patients had low baseline levels of α1-acid glycoprotein, a potential selective biomarker.

CONCLUSIONS

Filanesib 1.50 mg/m²/day administered with prophylactic filgrastim has a manageable safety profile and encouraging activity in heavily pretreated patients This study is registered at http://ift.tt/PmpYKN as NCT00821249. Cancer 2017. © 2017 American Cancer Society.

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