Selection and design of individualized treatments remains a key goal in cancer therapeutics; prediction of response and tumor recurrence following a given therapy provides a basis for subsequent personalized treatment design. We demonstrate an approach towards this goal with the example of photodynamic therapy (PDT) as the treatment modality and photoacoustic imaging (PAI) as a non-invasive, response and disease recurrence monitor in a murine model of glioblastoma (GBM). PDT is a photochemistry-based, clinically-used technique that consumes oxygen to generate cytotoxic species, thus causing changes in blood oxygen saturation (StO2). We hypothesize that this change in StO2 can be a surrogate marker for predicting treatment efficacy and tumor recurrence. PAI is a technique that can provide a 3D atlas of tumor StO2 by measuring oxygenated and deoxygenated hemoglobin. We demonstrate that tumors responding to PDT undergo approximately 85% change in StO2 by 24-hrs post-therapy while there is no significant change in StO2 values in the non-responding group. Furthermore, the 3D tumor StO2 maps predicted whether a tumor was likely to regrow at a later time point post-therapy. Information on the likelihood of tumor regrowth that normally would have been available only upon actual regrowth (10-30 days post treatment) in a xenograft tumor model, was available within 24-hrs of treatment using PAI, thus making early intervention a possibility. Given the advances and push towards availability of PAI in the clinical settings, the results of this study encourage applicability of PAI as an important step to guide and monitor therapies (e.g. PDT, radiation, anti-angiogenic) involving a change in StO2.

Vitamin D deficiency (≤20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma. A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of diagnosis was performed to determine whether vitamin D deficiency and repletion are associated with melanoma outcome. A total of 409 individuals diagnosed with histopathology-confirmed melanoma who had an ever measured serum 25(OH)D3 level were identified. 252 individuals with a 25(OH)D3 level recorded within one year after diagnosis were included in the study and the individual and melanoma characteristics such as age, sex, Breslow thickness, ulceration, stage, mitotic rate, and LDH were obtained from the medical record. A worse melanoma prognosis was associated with vitamin D deficiency (P=0.012), higher stage (P<0.001), ulceration (P=0.001), and higher mitotic rate (P=0.001) (HR 1.93, 95% CI 1.15-3.22). In patients with stage IV metastatic melanoma, vitamin D deficiency was associated with significantly worse melanoma-specific mortality (adjusted HR 2.06, 95% CI 1.10-3.87). Patients with metastatic melanoma who were initially vitamin D deficient and subsequently had a decrease or ≤20 ng/mL increase in their 25(OH)D3 concentration had significantly worse outcomes (HR 4.68, 95% CI 1.05-20.88) compared to non-deficient patients who had a >20 ng/mL increase. Our results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

Insulin therapy decline is common, potentially leading to progression of hyperglycaemia and a delay in achievement of glycaemic control. Further investigation is needed to determine the reasons, risk factors and long-term outcomes of this important clinical phenomenon.

This large-scale study strengthens the evidence that these two inflammatory conditions are truly associated and establishes their joint effect on overall morbidity, mortality, and resource utilization.