Diagnostic CT-Enabled Planning (DART): Results of a Randomized Trial in Palliative Radiation Therapy.

PURPOSE: Using diagnostic computed tomography (dCT) scans instead of CT simulation (CTsim) scans can increase departmental efficiency and reduce patient burden. The goal of the DART trial was to assess the efficacy and acceptability of dCT-based planning workflows with a focus on patient experiences, plan deliverability and adequacy of target coverage, and workflows. METHODS AND MATERIALS: Patients undergoing same-day CTsim and treatment for palliative radiation therapy to thoracic, abdominopelvic, or proximal limb targets with a recent dCT (within 28 days) in a reproducible position were eligible. After stratifying by target type (bone or soft tissue vs. visceral), participants were randomized (1:2 ratio) between CTsim-based (CTsim arm) vs. dCT-based planning (dCT arm). The primary endpoint was time in center (TIC), defined as total time spent in the cancer center on first day of treatment, from first radiation department appointment to first fraction completion. Secondary endpoints included plan deliverability, adequacy of target coverage, and stakeholder acceptability. RESULTS: Thirty-three patients (42 treatment sites) were enrolled between June 2022 and April 2023. The median age was 72 (interquartile range [IQR]: 67-78), 73% were male, and the most common primary cancers were lung (33%), prostate (24%), and breast (12%). The most common dose and fractionations were 8 Gy in 1 and 20 Gy in 5 fractions (50% and 43% of plans, respectively). TIC was 4.7 ± 1.1 hours (mean ± SD) in the CTsim arm vs. 0.41 ± 0.14 hours in the dCT arm (P < .001). All dCT plans were deliverable. All plans in both arms were rated as "acceptable" (80% CTsim; 81% dCT) or "acceptable with minor deviation" (20% CTsim; 19% dCT). Patient perception of acceptability was similar in both arms with the exception of time burden, which was rated as "acceptable" by 50% in the CTsim arm vs. 90% in the dCT arm (P = .025). CONCLUSION: dCT-based radiation planning substantially reduced TIC without detriment in plan deliverability or quality and had a tangible impact on patient experience with reduced patient-reported time burden.

Dose-response of localized renal cell carcinoma after stereotactic body radiation therapy: A meta-analysis.

BACKGROUND: Stereotactic ablative radiation therapy (SBRT) is an emerging treatment option for primary renal cell carcinoma (RCC), particularly in patients who are unsuitable for surgery. The aim of this review is to assess the effect of increasing the biologically equivalent dose (BED) via various radiation fractionation regimens on clinical outcomes. METHODS: A literature search was conducted in PubMed (Medline), EMBASE, and the Cochrane Library for studies published up to October 2023. Studies reporting on patients with localized RCC receiving SBRT were included to determine its effectiveness on local control, progression-free survival, and overall survival. A random effects model was used to meta-regress clinical outcomes relative to the BED for each study and heterogeneity was assessed by I2. RESULTS: A total of 724 patients with RCC from 22 studies were included, with a mean age of 72.7 years (range: 44.0-81.0). Local control was excellent with an estimate of 99 % (95 %CI: 97-100 %, I2 = 19 %), 98 % (95 %CI: 96-99 %, I2 = 8 %), and 94 % (95 %CI: 90-97 %, I2 = 11 %) at one year, two years, and five years respectively. No definitive association between increasing BED and local control, progression-free survival and overall survival was observed. No publication bias was observed. CONCLUSIONS: A significant dose response relationship between oncological outcomes and was not identified, and excellent local control outcomes were observed at the full range of doses. Until new evidence points otherwise, we support current recommendations against routine dose escalation beyond 25-26 Gy in one fraction or 42-48 Gy in three fractions, and to consider de-escalation or compromising target coverage if required to achieve safe organ at risk doses.

Immunotherapy and Radiation Therapy Sequencing in Breast Cancer: A Systematic Review.

PURPOSE: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an "abscopal effect." The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation. METHODS AND MATERIALS: We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy. RESULTS: Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT. CONCLUSIONS: In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.

Is Ultrahypofractionated Whole Pelvis Radiation Therapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Patients With Prostate Cancer? Early Results From the HOPE Trial.

OBJECTIVE: The aim of this work was to evaluate the acute toxicity and quality-of-life (QOL) impact of ultrahypofractionated whole pelvis radiation therapy (WPRT) compared with conventional WPRT fractionation after high-dose-rate prostate brachytherapy (HDR-BT). METHODS AND MATERIALS: The HOPE trial is a phase 2, multi-institutional randomized controlled trial of men with prostate-confined disease and National Comprehensive Cancer Network unfavorable intermediate-, high-, or very-high-risk prostate cancer. Patients were randomly assigned to receive conventionally fractionated WPRT (standard arm) or ultrahypofractionated WPRT (experimental arm) in a 1:1 ratio. All patients underwent radiation therapy with 15 Gy HDR-BT boost in a single fraction followed by WPRT delivered with conventional fractionation (45 Gy in 25 daily fractions or 46 Gy in 23 fractions) or ultrahypofractionation (25 Gy in 5 fractions delivered on alternate days). Acute toxicities measured during radiation therapy and at 6 weeks posttreatment were assessed using the clinician-reported Common Terminology Criteria for Adverse Events version 5.0, and QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC-50) and International Prostate Symptom Score (IPSS). RESULTS: A total of 80 patients were enrolled and treated across 3 Canadian institutions, of whom 39 and 41 patients received external radiation therapy with conventionally fractionated and ultrahypofractionated WPRT, respectively. All patients received androgen deprivation therapy except for 2 patients treated in the ultrahypofractionated arm. The baseline clinical characteristics of the 2 arms were similar, with 51 (63.8%) patients having high or very-high-risk prostate cancer disease. Treatment was well tolerated with no significant differences in the rate of acute adverse events between arms. No grade 4 adverse events or treatment-related deaths were reported. Ultrahypofractionated WPRT had a less detrimental impact on the EPIC-50 bowel total, function, and bother domain scores compared with conventional WPRT in the acute setting. By contrast, more patients treated with ultrahypofractionated WPRT reached the minimum clinical important difference on the EPIC-50 urinary domains. No significant QOL differences between arms were noted in the sexual and hormonal domains. CONCLUSIONS: Ultrahypofractionated WPRT after HDR-BT is a well-tolerated treatment strategy in the acute setting that has less detrimental impact on bowel QOL domains compared with conventional WPRT.

Treatment modalities to manage hepatocellular carcinoma patients with portal vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: A number of therapeutic treatment strategies exist for patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). The aim of this review is to provide a current understanding of treatment options and determine the relative effectiveness of treatment options in preventing mortality over 24 months. METHODS: A search was conducted in PubMed, EMBASE and Cochrane CENTRAL from 2007 to 2022. Articles were screened to identify those that reported on all-cause mortality among treated, non-palliative patients with HCC and PVT. Study quality was assessed using the Cochrane Risk of Bias in Non-Randomized Studies of Interventions tool (ROBINS-1). Mortality rates at prespecified timepoints between 6 and 24 months were extracted and summarized using a random-effects DerSimonian-Laird model. This review was registered a priori on PROSPERO (CRD42022290708). RESULTS: When comparing radiotherapy (RT) to sorafenib and combined transarterial chemoembolization (TACE), there was a trend that RT yields better survival at 6 months [odds ratio (OR) 0.70, 95% confidence interval (CI): 0.28-1.76]. When comparing sorafenib to Y90 and RT, sorafenib was associated with higher odds for mortality at 6 months (OR 2.20, 95% CI: 1.11-4.39). No significant differences were noticed from 12 to 24 months. CONCLUSIONS: Future strategies for HCC with PVT should look at the combination of radiation and systemic treatments either concurrently or sequentially.

Palliative radiotherapy for hepatic tumors: a narrative review of indications and recommendations.

BACKGROUND AND OBJECTIVE: Primary and metastatic liver cancer presents heterogeneously. New radiotherapy techniques have reduced toxicity concerns, leading to increased use of liver radiotherapy. This review synthesizes available evidence and offers recommendations for palliative radiotherapy for liver cancer. METHODS: PubMed, Ovid Medline, Embase, Cochrane Central, and Web of Science were searched from inception to December 28th, 2022. Articles reporting local control (LC), survival, toxicity, symptom control, and response after stereotactic body radiotherapy (SBRT), partial-liver, or whole-liver radiotherapy (WLRT) techniques were reviewed. We also identified nomograms identifying patients who may benefit from radiotherapy. KEY CONTENT AND FINDINGS: Nine randomized-controlled trials were found, in addition to many retrospective, feasibility, and phase I or II studies. Patients with favorable prognosis may receive SBRT using 30-50 Gray (Gy) in 3-5 fractions for primary cancer and up to 60 Gy for metastases, provided normal-tissue constraints are met. Select patients with multiple (>5) or large (>10 cm) lesions or macrovascular invasion (MVI) may be considered, but with potentially reduced LC and increased toxicity. Lower SBRT doses (i.e., 25 Gy in 5 fractions) can be considered on a cautionary basis for patients with poorer liver function or health. Patients with larger tumor burden, poor performance status (PS), or inability to tolerate SBRT positioning or motion-management can consider partial-liver three-dimensional conformal radiotherapy (3DCRT). For patients with extremely guarded prognosis and/or extremely poor performance, WLRT provides pain and symptom relief over several weeks. Combining radiotherapy and systemic therapy may allow radiotherapy de-escalation while maintaining good outcomes. CONCLUSIONS: Radiotherapy has a definite role for palliation of liver cancer with practical research providing guidance in the use of techniques and different regimens in various patient subgroups. Future investigation, including randomized trials, is needed to optimize patient selection, radiotherapy techniques, and integration with other therapies.

Prevalence and predictors of long-delayed (> 120 h) chemotherapy-induced nausea and vomiting (CINV)-a systematic review and individual patient data meta-analysis.

INTRODUCTION: Although there have been reports of chemotherapy-induced nausea and vomiting (CINV) beyond 120 h, its overall prevalence has not been systematically examined. The aim of this review and meta-analysis was to report on the prevalence of this long-delayed CINV. METHODS: This review was registered on PROSPERO (CRD42022346963). PubMed (Medline), Embase, and Cochrane Central were searched from inception until August 2022. Articles were included if they reported on CINV > 120 h after initiation of the chemotherapy regimen and patients received a single-agent highly emetogenic (HEC) or moderately emetogenic (MEC) antineoplastic agent for 1 day alone or in combination with low/minimal emetogenic chemotherapy. For all eligible articles, individual study authors were contacted and requested to provide individual patient-level data of demographics, emetogenicity of chemotherapy regimens, and daily incidence of nausea and vomiting. Forward stepwise logistic regression identified predictors for the incident day's CINV based on prior day's CINV episodes, controlling for patient demographics, and stratified by regimen emetogenicity. RESULTS: A total of 2048 patients from 2 studies were included in this individual patient data meta-analysis: 1333 patients (65%) received HEC and 715 (35%) received MEC. Among those receiving HEC, 325 (24%) experienced acute, 652 (49%) delayed, and 393 (31%) long-delayed nausea; 107 (8%) experienced acute, 179 (14%) delayed, and 79 (6%) long-delayed vomiting. Among those receiving MEC, 48 (7%) experienced acute, 272 (38%) delayed, and 167 (24%) long-delayed nausea; 12 (2%) experienced acute, 97 (14%) delayed, and 42 (6%) long-delayed vomiting. Nausea in the long-delayed phase was as severe as in the delayed phase. Patients experiencing nausea and vomiting on days 4 and 5 were at significant risk of experiencing long-delayed CINV. CONCLUSION: While not as prevalent as delayed nausea and vomiting, long-delayed CINV affects a significant proportion of patients and severity is similar. Patients with delayed CINV, specifically on days 4-5, are at risk of experiencing long-delayed CINV.

Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial.

OBJECTIVE: This study was undertaken to assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2-18 years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had ≥6 convulsive seizures during the 6-week baseline period were randomized to placebo, fenfluramine .2 mg/kg/day, or fenfluramine .7 mg/kg/day (1:1:1 ratio) administered orally (maximum dose = 26 mg/day). Doses were titrated over 2 weeks and maintained for an additional 12 weeks. The primary endpoint was a comparison of the monthly convulsive seizure frequency (MCSF) during baseline and during the combined titration-maintenance period in patients given fenfluramine .7 mg/kg/day versus patients given placebo. RESULTS: A total of 169 patients were screened, and 143 were randomized to treatment. Mean age was 9.3 ± 4.7 years (±SD), 51% were male, and median baseline MCSF in the three groups ranged 12.7-18.0 per 28 days. Patients treated with fenfluramine .7 mg/kg/day demonstrated a 64.8% (95% confidence interval = 51.8%-74.2%) greater reduction in MCSF compared with placebo (p < .0001). Following fenfluramine .7 mg/kg/day, 72.9% of patients had a ≥50% reduction in MCSF compared with 6.3% in the placebo group (p < .0001). The median longest seizure-free interval was 30 days in the fenfluramine .7 mg/kg/day group compared with 10 days in the placebo group (p < .0001). The most common adverse events (>15% in any group) were decreased appetite, somnolence, pyrexia, and decreased blood glucose. All occurred in higher frequency in fenfluramine groups than placebo. No evidence of valvular heart disease or pulmonary artery hypertension was detected. SIGNIFICANCE: The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of fenfluramine in children with Dravet syndrome.

A Phase 1 Two-Arm, Randomized, Double-Blind, Active-Controlled Study of Live, Oral Plasmid-Derived Adenovirus Type 4 and Type 7 Vaccines in Seronegative Adults.

PXVX0047 is an investigational vaccine developed for active immunization to prevent febrile acute respiratory disease (ARD) caused by adenovirus serotypes 4 (Ad4) and 7 (Ad7). PXVX0047 consists of a modernized, plasmid-derived vaccine that was generated using a virus isolated from Wyeth Ad4 and Ad7 vaccine tablets. A phase 1 two-arm, randomized, double-blind, active-controlled study was conducted to evaluate the safety profile and immunogenicity of the investigational adenovirus vaccines. The two components of PXVX0047 were administered orally together in a single dose to 11 subjects. For comparison, three additional subjects received the Ad4/Ad7 vaccine that is currently in use by the US military. The results of this study show that the tolerability and immunogenicity of the PXVX0047 Ad7 component are comparable with that of the control Ad4/Ad7 vaccine; however, the immunogenicity of the PXVX0047 Ad4 component was lower than expected. Clinical trial number NCT03160339.

What's to come in PSMA therapies and diagnostics: A summary of clinical trials involving PSMA radioligand-based therapeutic and/or diagnostic approaches with active recruitment.

INTRODUCTION: Prostate-Specific Membrane Antigen (PSMA)-based diagnostics and therapeutics are proving highly valuable in identifying disease sites and providing targeted radioligand therapy (RLT) for disseminated disease in prostate cancer (PC). With successful integration of these tools in limited PC presentations, there is a real need and excitement for trials testing PSMA-based approaches more broadly. AREAS COVERED: We review the ongoing trials registered on ClinicalTrials.gov which aim to evaluate PSMA-PET or PSMA-RLT applications. We outline clinical contexts which have significant ongoing study and therefore may see imminent change, as well as contexts which are lacking in study in the hopes of guiding future research. EXPERT OPINION: Trials examining intensification strategies through targeted radiotherapy, combination systemic therapies, and RLTs have the potential to demonstrate improved clinical outcomes using PSMA-PET CT for guidance. We expect that PSMA-PET will become fundamental in the work-up of patients before targeted radiotherapy or surgery. The results of ongoing trials will likely clarify the benefits of PSMA-RLT in metastatic PC including in oligometastatic and hormone-sensitive disease; however, there is a sparsity of trials evaluating PSMA-RLT outside of metastatic PC. Clinical trials with PSMA PET/CT as an endpoint for disease control are emerging and standardized reporting and metrics for PSMA staging and response will facilitate the inclusion of PSMA PET endpoints into therapeutic trials.

PET/MRI Assessment of Acute Cardiac Inflammation 1 Month After Left-Sided Breast Cancer Radiation Therapy.

Our purpose was to investigate the utility of 18F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18F-FDG SUVmean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUVmean in left anterior descending segments (P = 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P ≤ 0.02). Further, a significant reduction in left ventricular stroke volume (-7%) was seen (P < 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.

A Rare Case of Recurrent Cutaneous Non-Hodgkin's Lymphoma in the Extremity: Long-Term Follow-Up and Review of the Literature Written With the Assistance of ChatGPT.

Cutaneous involvement of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is uncommon. We report on a 71-year-old male with a history of CLL of the skin in the distal extremities. The patient presented with eruptions of new lesions on the toes of his feet bilaterally, causing significant pain that limited his mobility. Cutaneous involvement of CLL is a rare presentation, and management recommendations are largely based on case reports with limited follow-up. Furthermore, assessing the duration of response, response rates, and correct sequencing of treatment is difficult due to variable use and doses of treatment. The case was treated in 2001 when newer systemic treatments were not available. Therefore, the results can also be directly related to local treatments. Based on a literature review and this case, this report provides insight into the benefits and risks of local treatment for cutaneous involvement of CLL in the extremities and how radiation can be sequenced with other options such as surgical excision and chemotherapy.

A Taxonomically-verified and Vouchered Checklist of the Vascular Plants of the Republic of Guinea.

The Checklist of the Vascular Plants of the Republic of Guinea (CVPRG) is a specimen-based, expert-validated knowledge product, which provides a concise synthesis and overview of current knowledge on 3901 vascular plant species documented from Guinea (Conakry), West Africa, including their accepted names and synonyms, as well as their distribution and status within Guinea (indigenous or introduced, endemic or not). The CVPRG is generated automatically from the Guinea Collections Database and the Guinea Names Backbone Database, both developed and maintained at the Royal Botanic Gardens, Kew, in collaboration with the staff of the National Herbarium of Guinea. A total of 3505 indigenous vascular plant species are reported of which 3328 are flowering plants (angiosperms); this represents a 26% increase in known indigenous angiosperms since the last floristic overview. Intended as a reference for scientists documenting the diversity and distribution of the Guinea flora, the CVPRG will also inform those seeking to safeguard the rich plant diversity of Guinea and the societal, ecological and economic benefits accruing from these biological resources.

Dose-Escalated Radiotherapy Alone or in Combination With Short-Term Androgen Deprivation for Intermediate-Risk Prostate Cancer: Results of a Phase III Multi-Institutional Trial.

PURPOSE: It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT). METHODS: The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone-releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer-specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy. RESULTS: Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P <.001), DM (HR, 0.25; P <.001), PCSM (HR, 0.10; P = .007), and salvage therapy use (HR, 0.62; P = .025). Other-cause deaths were not significantly different (P = .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 (P <.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 (P = .29). CONCLUSION: STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.

Are Radiation Target Volumes for Postmastectomy Radiation Therapy Too Large? Initial Report of the Complication Avoidance of Reconstruction Implant Radiation Therapy (CARIT) Study.

Following mastectomy for breast cancer, women may choose implant-based reconstruction for many reasons, such as cosmesis, self-identity, and the ability to wear particular items of clothing. However, postmastectomy radiation therapy (PMRT) can compromise these cosmetic goals, including as much as a 40% loss of implant rate. To minimize the risk of radiation toxicity, it is important to consider how clinical target volumes (CTVs) can be optimized in PMRT to preserve the implant and reduce complications. Typically, guidelines from organizations such as the Radiation Oncology Group are used, which include regions previously encompassed by tangential fields. This includes all structures below the pectoralis muscle, such as the chest wall, where the risk of recurrence is negligible; this technique often requires incidental inclusion of portions of the lung and heart plus circumferential radiation of the implant. We present the preliminary single institution case series of a technique of complication avoidance of reconstruction implant radiation therapy, called CARIT, where the chest wall, and a large proportion of the implant, is not irradiated. In a retrospective review of 30 cases in which CARIT has been attempted, it was found that 24% of patients treated required a second surgery due to Baker grade III/IV capsular contracture. Using the Modified Harvard Harris Cosmetic Scale, 66.5% of patients had cosmetic outcomes rated as "good" or "excellent". CARIT could offer a technique to reduce complications in postmastectomy implant-based reconstruction patients, with our next steps focusing on improving dosimetry, and formally comparing the cosmesis and tumor control aspects with commonly used techniques.

Use of artificial intelligence for cancer clinical trial enrollment: a systematic review and meta-analysis.

BACKGROUND: The aim of this study is to provide a comprehensive understanding of the current landscape of artificial intelligence (AI) for cancer clinical trial enrollment and its predictive accuracy in identifying eligible patients for inclusion in such trials. METHODS: Databases of PubMed, Embase, and Cochrane CENTRAL were searched until June 2022. Articles were included if they reported on AI actively being used in the clinical trial enrollment process. Narrative synthesis was conducted among all extracted data: accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. For studies where the 2x2 contingency table could be calculated or supplied by authors, a meta-analysis to calculate summary statistics was conducted using the hierarchical summary receiver operating characteristics curve model. RESULTS: Ten articles reporting on more than 50 000 patients in 19 datasets were included. Accuracy, sensitivity, and specificity exceeded 80% in all but 1 dataset. Positive predictive value exceeded 80% in 5 of 17 datasets. Negative predictive value exceeded 80% in all datasets. Summary sensitivity was 90.5% (95% confidence interval [CI] = 70.9% to 97.4%); summary specificity was 99.3% (95% CI = 81.8% to 99.9%). CONCLUSIONS: AI demonstrated comparable, if not superior, performance to manual screening for patient enrollment into cancer clinical trials. As well, AI is highly efficient, requiring less time and human resources to screen patients. AI should be further investigated and implemented for patient recruitment into cancer clinical trials. Future research should validate the use of AI for clinical trials enrollment in less resource-rich regions and ensure broad inclusion for generalizability to all sexes, ages, and ethnicities.

Cancer-related fatigue-pharmacological interventions: systematic review and network meta-analysis.

INTRODUCTION: Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed. METHODS: Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model. RESULTS: This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil. CONCLUSION: Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.

Duloxetine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN): systematic review and meta-analysis.

INTRODUCTION: Duloxetine has previously been reported to be promising in the setting of chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to conduct a comprehensive systematic review and meta-analysis, on the use of duloxetine in prevention and treatment of CIPN. METHODS: PubMed, Embase and Cochrane CENTRAL were searched from database inception up until April 2022. Articles were included in this review if they reported on duloxetine use in the setting of CIPN, in a multiarm comparative human trial. A random effects DerSimonian-Laird model was used to calculate summary risk ratios (RR) and corresponding 95% CIs, comparing duloxetine to placebo. This review was registered on. RESULTS: Seven randomised controlled trials that included 645 patients were identified. Five reported on duloxetine for treatment of CIPN, and two for prevention of CIPN. Two studies had some concern for bias. Duloxetine was statistically similar to placebo in its efficacy, both in the treatment (RR 0.92, 95% CI 0.84 to 1.01) and prevention (RR 1.02, 95% CI 0.87 to 1.19) of CIPN. Safety profile was similar, in the treatment (RR 1.31, 95% CI 0.90 to 1.89) and prevention (RR 1.52, 95% CI 0.98 to 2.38) setting. CONCLUSION: There is currently limited evidence supporting duloxetine's use for CIPN. There is a need for more comprehensive and higher-quality trials assessing duloxetine in the setting of CIPN, before further clinical practice recommendations. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42022327487).

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: Interim analysis of an open-label extension study.

OBJECTIVE: This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS). METHODS: Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months. RESULTS: As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2-4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was -28.6% over the entire OLE (n = 241) and -50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was -45.9% (n = 192, p = .0038). Generalized tonic-clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%-44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%-41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed. SIGNIFICANCE: Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.