Post-neoadjuvant strategies in breast cancer: From risk assessment to treatment escalation

The post-neoadjuvant setting in early breast cancer represents an attractive scenario for adjuvant clinical trials, offering the opportunity to test new drugs or combinations in high-risk patients who did not achieve pathologic complete response after primary treatment. No standard therapies are routinely proposed to patients with residual disease after neoadjuvant chemotherapy and few trials have explored this setting. To date, only one randomized phase III study showed the benefit of additional capecitabine after neoadjuvant chemotherapy, and international guidelines recommend at least to consider its use, particularly for triple negative breast cancer. Therefore, the management of these patients is still a clinical challenge, with limited data supporting the use of an additional adjuvant non-cross-resistant chemotherapy. Escalation strategies are currently under evaluation, with new agents proposed as supplementary post-neoadjuvant treatment (e.g. platinum salts, capecitabine, poly ADP-ribose polymerase inhibitors, immune checkpoint inhibitors, cyclin-dependent kinase 4/6 inhibitors). Based on these premises, selection criteria are critical to identify patients who may benefit from post-neoadjuvant therapies, through the validation of prognostic and predictive biomarkers for a reliable risk assessment and estimation of benefit.The present review summarizes the efforts in introducing new therapeutic options for patients with breast cancer and residual disease after neoadjuvant treatment, with a particular focus on the ongoing clinical trials and useful biomarkers for risk stratification.     

Recent advances in the development of microparticles for pulmonary administration

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Analysis of radiation exposure data from common radiological procedures in Dutch hospitals

IntroductionIn the Netherlands, Diagnostic Reference Levels (DRLs) have not been based on a national survey as proposed by ICRP. Instead, local exposure data, expert judgment and the international scientific literature were used as sources. This study investigated whether the current DRLs are reasonable for Dutch radiological practice.MethodsA national project was set up, in which radiography students carried out dose measurements in hospitals supervised by medical physicists. The project ran from 2014 to 2017 and dose values were analysed for a trend over time. In the absence of such a trend, the joint yearly data sets were considered a single data set and were analysed together. In this way the national project mimicked a national survey.ResultsFor six out of eleven radiological procedures enough data was collected for further analysis. In the first step of the analysis no trend was found over time for any of these procedures. In the second step the joint analysis lead to suggestions for five new DRL values that are far below the current ones. The new DRLs are based on the 75 percentile values of the distributions of all dose data per procedure.ConclusionThe results show that the current DRLs are too high for five of the six procedures that have been analysed. For the other five procedures more data needs to be collected. Moreover, the mean weights of the patients are higher than expected. This introduces bias when these are not recorded and the mean weight is assumed to be 77 kg.Implications for practiceThe current checking of doses for compliance with the DRLs needs to be changed. Both the procedure (regarding weights) and the values of the DRLs should be updated.     

Radiation Therapy for Pediatric Brain Tumors using Robotic Radiation Delivery System and Intensity Modulated Proton Therapy

PurposeThis study recruited 2 centers with expertise in treating pediatric brain tumors with robotic radiation delivery system photon therapy and proton therapy, respectively, to study the plan quality and dose deposition characteristics of robotic radiation delivery system photon therapy and intensity modulated proton therapy (IMPT) plans.Methods and MaterialsA total of 18 patients clinically treated with the robotic radiation delivery system were planned with IMPT. Cases were planned per the standard of care of each institution but respected the same planning objectives. The comparison included 3 aspects: plan quality, dose fall-off characteristics around the target volume, and the volume of the high-, intermediate-, and low-dose baths.ResultsAll robotic radiation delivery system and IMPT plans met the planning objectives. However, IMPT significantly reduced the maximum dose to organs at risk away from the planning target volume (PTV), such as the cochlea and eye (P < .05), and the mean dose to the normal brain (P < .05). No statistically significant difference was observed in the maximum dose to the optical pathway and brain stem. Robotic radiation delivery system plans demonstrated a sharper dose fall-off within 5 mm around the PTV (P < .05), whereas IMPT significantly lowered the dose to the normal tissue beyond 10 mm from the PTV (P < .05). The robotic radiation delivery system offers a smaller high-dose bath whereas IMPT offers a smaller low-dose bath (P < .05). However, the difference in intermediate dose is not statistically significant.ConclusionsIn general, robotic radiation delivery system plans exhibit reduced high-dose exposure to normal tissue, and IMPT plans have considerably smaller volumes of low-dose exposure with differences in medium-range dose baths increasingly favoring protons as tumor size increases.     

Using recreational cannabis to treat insomnia: Evidence from over-the-counter sleep aid sales in Colorado

This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store scanner data in a multivariable panel regression design were used to compare the change in the monthly market share of sleep aids with varying dispensary-based recreational cannabis access (existence, sales, and count) in Colorado counties between 12/2013 and 12/2014. We measured annually-differenced market shares for sleep aids as a portion of the overall OTC medication market, thus accounting for store-level demand shifts in OTC medication markets and seasonality, and used the monthly changes in stores’ sleep aid market share to control for short-term trends. Relative to the overall OTC medication market, sleep aid market shares were growing prior to recreational cannabis availability. The trend reverses (a 236% decrease) with dispensary entry (−0.33 percentage points, 95% CI −0.43 to −0.24, p < 0.01) from a mean market share growth of 0.14 ± 0.97. The magnitude of the market share decline increases as more dispensaries enter a county and with higher county-level cannabis sales. The negative associations are driven by diphenhydramine- and doxylamine-based sleep aids rather than herbal sleep aids and melatonin. These findings support survey evidence that many individuals use cannabis to treat insomnia, although sleep disturbances are not a specific qualifying condition under any U.S. state-level medical cannabis law. Investigations designed to measure the relative effectiveness and side effect profiles of conventional OTC sleep aids and cannabis-based products are urgently needed to improve treatment of sleep disturbances while minimizing potentially serious negative side effects.