The present study describes the optimization of 68Ga radiolabeling with PAMAM dendrimer–DOTA conjugate. A conjugate (PAMAM–DOTA) concentration of 11.69 µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0 min and reaction temperature ranging between 90 and 100 °C. The decay corrected radiochemical yield was found to be 79.47 ± 0.01%. The radiolabeled preparation ([68Ga]-DOTA–PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0 h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1 h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good ‘non-specific’ tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA–PAMAM-D conjugation with αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the 68Ga labeled product for imaging and treating angiogenesis respectively.

BackgroundOral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. ObjectivesTo determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes. Search methodsElectronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 1st December 2010. Reference lists of recent reviews and included studies were also searched to identify further trials. Selection criteriaRandomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included. 1 Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy (Review)

Background. In Ontario, Canada, patient reported outcomes (PRO) evaluation through Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV non-small cell lung cancer (NSCLC) is associated with substantial disease and treatment-related morbidity, this province-wide study investigated moderateto-severe symptom burden in this population. Methods. ESAS collected from stage IV NSCLC patients diagnosed between 2007-2018 linked to Ontario provincial healthcare system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate-to-severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderateto-severe scores were identified using multivariable Poisson regression models with robust error variance. Results. Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, high comorbidity, and not receiving active cancer therapy had lower ESAS completion. Majority (94.4%) reported at least 1 moderate-to-severe symptoms. Most prevalent were tiredness (84.1%), low wellbeing (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis, while declining, remained high in the following year.On multivariable analyses, comorbidity, low income, non-immigrants, and urban residency were associated with moderate-to-severe symptoms. Moderate-to-severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, while drowsiness, low appetite and wellbeing, nausea, and tiredness were associated with systemic therapy within 2 weeks prior. Conclusion. This province-wide PRO analysis showed moderate-to-severe symptoms were prevalent and persistent among metastatic NSCLC patients, underscoring the need to address supportive measures in this population especially around treatments. The Oncologist ;9999:• • Implications for Practice: This is the largest patient reported outcome (PRO) results among lung cancer patients worldwide. Our results demonstrated the worse moderate-to-severe symptoms among stage IV non-small cell lung cancer patients compared to other patients with metastatic, other malignancies such as breast, gastric, or esophageal cancers assessed with similar methodology. These patients symptom severity also peaked early, and persistently high during 1 year follow-up. Symptoms burden was also associated with recent radiation and systemic treatments. This emphasized the importance of early and sustained PRO collection to detect actionable symptom progression, especially around treatments. Moreover, PRO

Background: Clinical benefit scores (CBS) are key elements of the ASCO Value Framework (ASCO-VF) and are weighted based on a hierarchy of efficacy endpoints: hazard ratio for death (HR OS), median overall survival (mOS), HR for disease progression (HR PFS), median progression-free survival (mPFS), and response rate (RR). When HR OS is unavailable, the other endpoints serve as “surrogates” to calculate CBS. CBS are computed from PFS or RR in 39.6% of randomized controlled trials. This study examined whether surrogate-derived CBS offer unbiased scoring compared with HR OS–derived CBS. Methods: Using the ASCO-VF, CBS for advanced disease settings were computed for randomized controlled trials of oncology drug approvals by the FDA, European Medicines Agency, and Health Canada in January 2006 through December 2017. Mean differences of surrogate-derived CBS minus HR OS–derived CBS assessed the tendency of surrogate-derived CBS to overestimate or underestimate clinical benefit. Spearman’s correlation evaluated the association between surrogate- and HR OS–derived CBS. Mean absolute error assessed the average difference between surrogate-derived CBS relative to HR OS–derived CBS. Results: CBS derived from mOS, HR PFS, mPFS, and RR overestimated HR OS–derived CBS in 58%, 68%, 77%, and 55% of pairs and overall by an average of 5.62 (n=90), 6.86 (n=110), 29.81 (n=101), and 3.58 (n=108), respectively. Correlation coefficients were 0.80 (95% CI, 0.70–0.86), 0.38 (0.20–0.53), 0.20 (0.00–0.38), and 0.01 (–0.18 to 0.19) for mOS-, HR PFS–, mPFS-, and RR-derived CBS, respectively, and mean absolute errors were 11.32, 12.34, 40.40, and 18.63, respectively. Conclusions: Based on the ASCO-VF algorithm, HR PFS–, mPFS-, and RR-derived CBS are suboptimal surrogates, because they were shown to be biased and poorly correlated to HR OS–derived CBS. Despite lower weighting than OS in the ASCO-VF algorithm, PFS still overestimated CBS. Simple rescaling of surrogate endpoints may not improve their validity within the ASCO-VF given their poor correlations with HR OS–derived CBS.