Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.

Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg.

The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma.

We report a case in which a renal transplant recipient with metastatic melanoma had an excellent response to treatment with second line programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab. Acute cellular allograft rejection on initiation of PD-1 inhibitor was successfully reversed with methylprednisolone. By converting the patient to sirolimus and giving predose prednisolone, pembrolizumab was continued with stable renal function and an excellent oncological response.

Discordance between oncotype DX recurrence score and RSPC for predicting residual risk of recurrence in ER-positive breast cancer.

Purpose: Oncotype DX, a gene expression assay widely employed to aid decision making on adjuvant chemotherapy use in patients with primary oestrogen receptor-positive (ER+) breast cancer, produces a recurrence score (RS) related to distant disease recurrence (DR) risk (RS%). In node-negative patients, RS can be integrated with clinicopathological parameters to derive RS-pathology-clinical (RSPC) that improves prognostic accuracy.

Methods: Data were collected on patients having clinically indicated tests with an intermediate clinical risk of distant recurrence, and for whom the decision to prescribe chemotherapy remained unclear.

Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease.

Purpose: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with prior implications in prognosis or treatment resistance. The secondary aim was to determine the prognostic impact in residual disease of the genes' expression.

Experimental Design: Expression levels of 24 genes were quantified by NanoString nCounter on formalin-fixed paraffin-embedded residual tumors from 126 patients treated with NAC and 56 paired presurgical biopsies.

Histology-Driven Therapy: The Importance of Diagnostic Accuracy in Guiding Systemic Therapy of Soft Tissue Tumors.

Soft tissue tumors (STTs) are rare mesenchymal neoplasms accounting for less than 1% of adult cancers. More than 50 different subtypes of STTs have been identified, with this number expected to grow as our understanding of the complex genetic landscape of these diseases improves. As the classification of soft tissue neoplasms continues to diversify, so does the approach to therapy.

Predicting response to cytotoxic drugs--the endocrine part of the story.

The substantial reduction in risk of recurrence and mortality in premenopausal breast cancer patients of estrogen deprivation as treatment for early ER+ breast cancer is well accepted. Surgical, radiotherapeutic or medical approaches to ovarian ablation/suppression all seem to be similarly effective and appear to be at least partially additive to the reduction seen with chemotherapy. Cytotoxic treatment of premenopausal women also frequently elicits a reduction in frequency and regularity of menstruation and sometimes a complete and permanent amenorrhea as a reflection of reduced ovarian activity.

Targeting endocrine resistance: is there a role for mTOR inhibition?

The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a critical intracellular signaling cascade that mediates both growth factor-induced proliferation and cell survival with deregulated signaling through this pathway, a feature of most cancers. Here, we review the role of the PI3K/Akt/mTOR pathway in endocrine-resistant breast cancer and discuss preclinical and clinical studies combining endocrine therapy with mTOR inhibition. Key to the success of such an approach will be a clinical trial design incorporating appropriate tumor selection and validation of biomarkers predicting benefit.

The effect of training distinct neurofeedback protocols on aspects of cognitive performance.

The use of neurofeedback as an operant conditioning paradigm has disclosed that participants are able to gain some control over particular aspects of their electroencephalogram (EEG). Based on the association between theta activity (4-7 Hz) and working memory performance, and sensorimotor rhythm (SMR) activity (12-15 Hz) and attentional processing, we investigated the possibility that training healthy individuals to enhance either of these frequencies would specifically influence a particular aspect of cognitive performance, relative to a non-neurofeedback control-group. The results revealed that after eight sessions of neurofeedback the SMR-group were able to selectively enhance their SMR activity, as indexed by increased SMR/theta and SMR/beta ratios.