PSMA-PET/CT-Guided Intensification of Radiation Therapy for Prostate Cancer (PSMAgRT): Findings of Detection Rate, Effect on Cancer Management, and Early Toxicity From a Phase 2 Randomized Controlled Trial.

PURPOSE: Prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET) is increasingly integrated in prostate cancer management because of its diagnostic performance. We sought to evaluate the effect of PSMA-PET/computed tomography (CT)-guided intensification of radiation therapy (PSMAgRT) on patient outcomes. Here, we report secondary trial endpoints including the rate of new lesion detection, effect on prostate cancer management, and treatment-related toxicities. METHODS AND MATERIALS: In this phase 2 cohort multiple randomized controlled trial across 2 institutions, men with prostate cancer planned for RT were randomly selected for PSMAgRT across 4 strata: oligometastatic, high risk (Cancer of the Prostate Risk Assessment ≥6 or cN1), salvage post-RT, and salvage postprostatectomy (RP). Primary endpoint was failure-free survival at 5 years, with analysis pending further follow-up. Secondary endpoints included new lesion detection yield of PSMA-PET/CT, acute and delayed toxicities, effect on prostate cancer management, and health-related quality-of-life outcomes. This trial is registered with ClinicalTrials.gov, identifier NCT03525288, companion to registry NCT03378856. RESULTS: Between May 2018 and February 2021, 262 patients were enrolled and randomized. Nine patients were later excluded (5 control, 4 PSMAgRT), leaving 253 patients for analysis (23 oligometastatic, 86 high risk, 16 salvage post-RT, and 128 salvage post-RP). New lesions were detected in 45.5% of oligometastatic, 39.5% of high risk, 14.3% of salvage post-RT, and 51.6% of salvage post-RP. Overall, PSMA-PET/CT led to intensification of RT in over half of patients (52.0%), with minimal intensification of systemic therapy (4.0%). With a median follow-up of 12.9 months, this intensification was associated with 3 attributable grade 3+ events (2.5% of patients undergoing PSMAgRT) but no difference in the rate of grade 2+ events attributable to RT compared with controls (43%, both arms). CONCLUSIONS: In this randomized trial, PSMA-PET/CT led to intensification of RT in more than half of patients. Longer follow-up is required to determine whether this intensification translates to effect on cancer control and long-term toxicity and health-related quality-of-life outcomes.

Induction of Ucp2 expression in brain phagocytes and neurons following murine toxoplasmosis: an essential role of IFN-gamma and an association with negative energy balance.

A model of murine toxoplasmosis was used to study cellular and temporal expression of uncoupling protein-2 (Ucp2) in the brain. In situ hybridization indicated that Ucp2 was located in neurons. Nuclei structures involved in energy balance, in particular the nucleus of the solitary tract (NST), was shown to have a positive association between negative energy balance and Ucp2 levels. Infection-induced Ucp2 expression colocalized mainly with microglial cells, but also with infiltrating macrophages and neutrophils in the brain, which was evident from day 9 post-infection. Using cytokine knockout mice we demonstrate that microglial Ucp2 induction in the brain was largely dependant on interferon-gamma, but not interleukin-6 or tumour-necrosis-factor-alpha in response to infection. In summary, this study shows that Ucp2 is regulated in a different manner in neurons than in microglia/phagocytes following infection. Our study indicates that an association exists between negative energy balance and neuronal Ucp2 levels in the NST, in particular.

Benefits of improving processes in cancer care with a care pathway-based electronic medical record.

PURPOSE: We analyzed the intermediate and longer term changes in patients' waiting times following the implementation of an electronic medical record (EMR) dedicated to ambulatory treatment in both medical and radiation oncology. METHODS AND MATERIALS: A pre-post study design was developed to assess improvements in patients' waiting times, defined as the number of days between key steps in patient management preceding the first treatment. The postperiod began 1 year after the EMR go-live to allow for a preliminary period of adjustment to the new EMR. The EMR under study was closely integrated into the clinicians' workflow, being designed as a care pathway information system to provide real-time support to the coordination of the entirety of care processes involving all the care personnel. RESULTS: The large majority of the waiting-time indicators decreased over time, with decreases ranging from 2 to 28 days. However, an important time lag was necessary to see an improvement, to the extent that better access was only observed in the final months of the postperiod. CONCLUSION: The study highlights the potential to design EMR applications that capitalize on tight workflow integration, both in medical and radiation oncology, to deal with the fundamentally collaborative nature of cancer care delivery.

Kainic acid upregulates uncoupling protein-2 mRNA expression in the mouse brain.

Intraperitoneal injection of kainic acid (KA) in C57BL/6J and 129T2SvEmsJ mice led to a transient induction of uncoupling protein-2 (Ucp2) mRNA expression in several brain regions, which included the CA1 subfield of the hippocampus, the dorsal endopiriform nucleus and the piriform cortex in both strains. In all those regions, levels of Ucp2 mRNA expression, as determined by in situ hybridization, peaked at 24 h and returned to basal levels within 72 h post-injection. The increase in mRNA expression was mainly observed in neurons, with microglial cells displaying only scattered expression of the gene. The neuronal induction of Ucp2 in response to KA was stronger in 129T2SvEmsJ mice than in C57BL/6J, which suggests a role for Ucp2 in excitotoxic challenges and neuroprotection.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

BACKGROUND: In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. METHODS: The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). RESULTS: Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. CONCLUSION: This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria.

Associated factors with adherence to antiepileptic drug in the capital city of Lao PDR.

Available medical care for epilepsy and antiepileptic drugs (AED) are provided in Vientiane Municipality by district hospitals supported by a non-governmental organization, which is referred to as a community-based intervention (CB), and reference hospital which is referred to as hospital-based interventions (HB). Identifying underlying factors of AED adherence is of public health interest. A community-based cross-sectional survey among randomly selected patients with epilepsy (PWE) who were being cared in Vientiane Municipality was undertaken in 2010. The Morisky scale was used to assess the level of adherence. Univariate and multivariate logistic regression analyses were performed to address predictive factors. Overall, 99 PWE were included in the study. Overall adherence was estimated at 57.6%, 57.1% and 58.0% for the HB and CB group, respectively. High level of adherence was related to illiteracy, being on monotherapy and experiencing fewer seizures. Implementing closer medical care at primary level to PWE improves the likelihood of reducing primary and secondary treatment gap which is related to PWEs' adherence. An active intervention through a downstream channel of training of medical health staff from reference level to community level enhances the prescription of adequate AED, the improvement of the quality of relation between PWE and medical staff.

Simultaneous integrated boost using intensity-modulated radiotherapy compared with conventional radiotherapy in patients treated with concurrent carboplatin and 5-fluorouracil for locally advanced oropharyngeal carcinoma.

PURPOSE: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. METHODS AND MATERIALS: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. RESULTS: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. CONCLUSIONS: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

The role of computed tomography in the management of the neck after chemoradiotherapy in patients with head-and-neck cancer.

PURPOSE: The aim of this study was to describe the outcome in patients with head-and neck-squamous cell carcinoma (HNSCC) followed up without neck dissection (ND) after concomitant chemoradiotherapy (CRT) based on computed tomography (CT) response. The second objective was to establish CT characteristics that can predict which patients can safely avoid ND. METHODS AND MATERIALS: Between 1998 and 2007, 369 patients with node-positive HNSCC were treated with primary CRT at our institution. After a clinical and a radiologic evaluation based on CT done 6 to 8 weeks after CRT, patients were labeled with a complete neck response (CR) or with a partial neck response (PR). RESULTS: The median follow-up was 44 months. The number of patients presenting with N3, N2, or N1 disease were 54 (15%), 268 (72%), and 47 (13%), respectively. After CRT, 263 (71%) patients reached a CR, and 253 of them did not undergo ND. Ninety-six patients reached a PR and underwent ND. Of those, 34 (35%) had residual disease on pathologic evaluation. A regression of the diameter of ≥ 80% and a residual largest diameter of 15 mm of nodes had negative pathologic predictive values of 100% and 86%, respectively. The 3-year regional control and survival rates were not different between patients with CR who had no ND and patients with PR followed by ND. CONCLUSION: Node-positive patients presenting a CR as determined by CT evaluation 6 to 8 weeks after CRT had a low rate of regional recurrence without ND. This study also suggests that lymph node residual size and percentage of regression on CT after CRT may be useful criteria to guide clinical decisions regarding neck surgery. Those results can help diminish the number of ND procedures with negative results and their associated surgical complications.

Enteral feeding during chemoradiotherapy for advanced head-and-neck cancer: a single-institution experience using a reactive approach.

PURPOSE: The optimal method for providing enteral nutrition to patients with head-and-neck cancer is unclear. The purpose of the present study was to evaluate the safety and efficacy of our reactive policy, which consists of the installation of a nasogastric (NG) feeding tube only when required by the patient's nutritional status. METHODS AND MATERIALS: The records of all patients with Stage III and IV head-and-neck cancer treated with concomitant chemotherapy and radiotherapy between January 2003 and December 2006 were reviewed. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The present study included 253 patients, and the median follow-up was 33 months. At 3 years, the estimated overall survival and disease-free survival rate was 82.8% and 77.8%, respectively, for the whole population. No survival difference was observed when the patients were compared according to the presence and absence of a NG tube or stratified by weight loss quartile. The mean weight loss during treatment for all patients was 10.4%. The proportion of patients requiring a NG tube was 49.8%, and the NG tube remained in place for a median duration of 40 days. No major complications were associated with NG tube installation. Only 3% of the patients were still dependent on enteral feeding at 6 months. CONCLUSION: These results suggest that the use of a reactive NG tube with an interdisciplinary team approach is a safe and effective method to manage malnutrition in patients treated with concomitant chemotherapy and radiotherapy for head-and-neck cancer.

Children's access to treatment for epilepsy: experience from the Lao People's Democratic Republic.

Epilepsy affects an estimated 10.5 million children worldwide, of whom 80% live in developing countries. The treatment gap is estimated at around 90% in the Lao People's Democratic Republic (Lao PDR). The present work analyses some of the reasons that could explain the low access to antiepileptic drugs (AED) for children with epilepsy in the Lao PDR. Epilepsy, the 'mad pig disease', is highly neglected. Traditional beliefs, fear and stigma are common among the general population and shared by 40% of health staff. Poor knowledge of the disease and its treatment, low trust in modern treatment, restricted access to AED and ignorance of long-term treatment explain the low access to AED. Improving understanding of epilepsy and its treatment, will improve the treatment gap for epileptic children in the Lao PDR.

Concurrent chemoradiation with carboplatin-5-fluorouracil versus cisplatin in locally advanced oropharyngeal cancers: is more always better?

PURPOSE: The optimal chemotherapy regimen remains undefined in the treatment of locally advanced oropharyngeal cancer by concomitant chemoradiation. This article compares two platinum-based chemotherapy regimens. METHODS AND MATERIALS: In this retrospective study, we reviewed all consecutive patients treated for Stage III or IVA-B oropharyngeal cancer using either a combination of carboplatin and 5-fluorouracil (5FU) every 3 weeks or high-dose cisplatin every 3 weeks concomitant with definitive radiation therapy. RESULTS: A total of 200 patients were treated with carboplatin-5FU and 53 patients with cisplatin. Median potential follow-up was 43 months. The 3-year overall survival rates for carboplatin-5FU and cisplatin respectively were 79.1% and 74.9% (p = 0.628), the 3-year disease-free survival rates were 76.0% and 71.3% (p = 0.799), and the 3-year locoregional control rates were 88.4% and 94.2% (p = 0.244). CONCLUSIONS: We could not demonstrate differences between these two regimens, which both proved efficacious. Polychemotherapy and monochemotherapy therefore seem comparable in this retrospective analysis.