Ciara Marie Kelly

Moving beyond Karnofsky and ECOG Performance Status Assessments with New Technologies

Progress in cancer research is coupled with increased treatment complexity reliant upon accurate patient selection. Oncologists rely upon measurement instruments of functional performance such as the Karnofsky or Eastern Cooperative Oncology Group Performance Status scales that were developed over fifty years ago to determine a patients suitability for systemic treatment. These standard assessment tools have been shown to correlate with response to chemotherapy, chemotherapy tolerability, survival, and quality of life of cancer patients. However, these scales are subjective, subject to bias and high interobserver variability. Despite these limitations important clinical decisions are based on PS including eligibility for clinical trials, the “optimal” therapeutic approach in routine practice, and the allocation of healthcare resources. This paper reviews the past, present, and potential future of functional performance status assessment in an oncology setting. The potential ability of electronic activity monitoring systems to provide an objective, accurate measurement of patient functional performance is explored. Electronic activity monitoring devices have the potential to offer positive health-related opportunities to patients; however their introduction to the healthcare setting is not without difficulty. The potential role of this technology in healthcare and the challenges that these new innovations pose to the healthcare industry are also examined.

Targeted Therapy in Older Patients With Solid Tumors

The introduction of targeted therapy has ushered in the era of personalized medicine in cancer therapy. The increased understanding of tumor heterogeneity has led to the determination of specific targets that can be exploited in treatment. This review highlights approved drugs in different therapeutic classes, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, drugs targeted to the human epidermal growth factor receptor 2, BRAF-mutation targeted drugs, anti-epidermal growth factor receptor inhibitors, and anti-vascular endothelial growth factor therapy. There have not been elderly patient-specific trials of these therapies. Most of the data are extrapolated from larger trials in which older patients generally were a fraction of the participants. Therapeutic recommendations are made on the basis of this analysis with the recognition that the older clinical trial participants may not be representative of patients seen in daily practice. Patient selection and geriatric evaluation are critical for appropriate drug selection, dosing, and monitoring. With care, these therapies are a major step forward in the safe and effective treatment of older patients with cancer.

From Shelf to Bedside-Wearable Electronic Activity Monitoring Technologies Might Assist Oncologists in Functional Performance Status Assessment of Older Cancer Patients.

Progress in cancer research has resulted in increasingly complex treatment options; thus, accurate patient selection for cancer therapeutic approaches is now more important than ever. The standard measurement tools used to assess cancer patients’ fitness for treatment were developed > 50 years ago, and these methods are subjective and subject to bias. New methods to assess the functional performance of cancer patients are needed. Wearable electronic activity monitors can provide objective assessments of patient activity levels in cancer patients over a prolonged period. Electronic activity monitoring device (EAMD)captured data provide additional information beyond that provided by standard measurements of patient performance status (PS). EAMD assessments, together with standard PS measurements, can provide a more accurate and objective assessment of the fitness of cancer patients. This could result in more appropriate patient selection for cancer treatment and improve patient outcomes.

Complete Responses to Mitotane in Metastatic Adrenocortical Carcinoma—A New Look at an Old Drug

PURPOSE Based largely on reports that predate modern reporting standards, mitotane has been considered a systemic treatment option for both hormone control and antitumor control of metastatic adrenocortical cancer (ACC), although the therapeutic window is narrow. METHODS We searched electronic medical records to identify patients with metastatic ACC treated and prescribed single-agent mitotane at Memorial Sloan Kettering Cancer Center from March 15, 1989-September 18, 2015. Reference radiologists reviewed all imaging and determined efficacy according to Response Evaluation Criteria in Solid Tumors 1.1. Patient demographics, toxicities, and treatment outcomes were reviewed. Next-generation sequencing was performed in selected cases. RESULTS Thirty-six patients were identified. The mean age was 54 and 50% had functional tumors. Grade 3 or greater toxicities were documented in 16 out of 36 patients (44%) and 17% had documented long term adrenal insufficiency. Progression of the disease as the best response occurred in 30 out of 36 patients (83%) and one patient (3%) experienced clinical progression. Three patients achieved a complete response (CR) (8%), one patient achieved a partial response (3%), and one patient (3%) had stable disease after slow disease progression prior to initiation of therapy (durable for 6 months). All responders had nonfunctional tumors. Next-generation sequencing in two of the three CR patients was performed and failed to identify any novel alterations. CONCLUSION In this retrospective series, mitotane had a low response rate and low tumor control rate; however, a disproportionately high complete response rate suggested it should be used in selected individuals. Adrenal insufficiency is common with mitotane use and aggressive treatment with steroid supplementation should be considered when appropriate to avoid excess toxicities. Biomarkers are desperately needed to further define this disease. IMPLICATIONS FOR PRACTICE This is the first objective report of single-agent mitotane using modern objective criteria. Although the vast majority of patients did not respond (and toxicity was high), we identified a remarkable 8% complete response rate (i.e. cure) in biopsy proven stage IV adrenocortical cancer patients. Biomarkers are desperately needed for this rare disease.

Liver-directed therapy in metastatic colorectal cancer

ABSTRACT Introduction: Colorectal cancer is a significant global health issue with over 1 million cases diagnosed annually throughout the world. 15% of patients diagnosed with colorectal cancer will have liver metastases and 60% will develop liver metastases if they have metastatic disease. Oligometastatic colorectal cancer confined to the liver represents an intermediate state in the evolution of metastatic capacity that opens the opportunity for local interventions. Areas covered: The literature supports long-term survival if patients undergo liver resection of colorectal metastases. This article reviews the liver-directed therapeutic strategies available for the management of metastatic liver disease including hepatic arterial infusion therapy, radiofrequency ablation, radiation therapy and transarterial chemoembolization. Expert commentary: Great advances have been made with the use of liver directed therapies. In the USA using hepatic arterial infusions with FUDR and Decadron along with systemic therapy, 5 year survivals after liver resection have improved. In Europe with the use of HAI of Oxaliplatin, more patients have been able to get to resection and have obtained higher survival rates, even in second line therapy. New advances in ablative therapy have improved results to get all disease treated at resection for the treatment of reccurrence

Borderline resectable pancreatic adenocarcinoma, is conversion therapy realistic?

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HER2: An emerging target in colorectal cancer

Despite advances in the treatment of metastatic colorectal cancer (CRC) the 5-year survival of patients with this disease remains low. A small proportion of CRCs overexpress the HER2 oncogene and the effective targeting of this pathway in other malignancies such as breast and gastric cancer has led to efforts to determine if it can also be exploited as a target in CRC. Activation of the HER2 pathway as a bypass signalling pathway has been identified as a mechanism of resistance for antiepidermal growth factor receptor antibody therapy in both the first line and salvage settings. It has also been shown that RAS and BRAF wild type metastatic CRC enriches for the presence of HER2 amplification. This knowledge, in addition to preclinical data providing a rationale for dual anti-HER2 targeted therapy has led to several clinical trials. To date, recently published and presented early phase data provide promising evidence suggesting anti-HER2 therapy may have a potentially beneficial role in the treatment of HER2-positive metastatic CRC. Namely, the HERACLES-A and MyPathway studies have shown benefit in a small number of patients with the use of combination trastuzumab-lapatinib and trastuzumab-pertuzumab, respectively. However, data from larger clinical trials are required before HER2-directed therapy is incorporated into standard treatment paradigms for CRC. This review presents an overview of epidermal growth factor receptor and HER2 pathways in CRC and discusses preclinical and clinical studies carried out in this field to date. There is potential that with continued evolution of data in this area, HER2 may become a validated therapeutic target and thus, anti-HER2 therapy may become an additional treatment option for a small population of patients with metastatic CRC.