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Gemcitabine is a chemotherapeutic agent used in a wide variety of solid tumours. Known side effects include a dose-limiting myelosuppressive toxicity, mild rash, and radiation-dependent dermatitis. Rarely, localized inflammation in the form of pseudocellulitis has also been observed. We present the case of a 77-year-old woman with a history of a Whipple procedure for pancreatic adenocarcinoma who presented to the emergency department after the start of gemcitabine therapy with increased erythema, swelling, and tenderness in her lower legs. Relevant past medical history included peripheral vascular disease, dyslipidemia, and hypertension. A diagnosis of gemcitabine-induced pseudocellulitis aggravated by venous stasis was confirmed after an extensive workup. This case report and the literature review describe this rare reaction, highlighting the need for increased recognition to avoid unnecessary therapeutic intervention. [ABSTRACT FROM AUTHOR]

Recent efforts aimed to add ICI to chemotherapy in the neoadjuvant and adjuvant setting (Neo/Adj) to improve outcomes of patients with resectable NSCLC. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of such strategy and identify subgroups of patients who may derive the most benefit. Randomized control trials comparing Neo/Adj ICI plus chemotherapy vs chemotherapy alone in resectable NSCLC (pre-Sep 2022) were retrieved from PubMed, Embase, Cochrane Library and updated based on recent conferences. Primary outcomes were pathological complete response (pCR), event-free, disease-free, and progression-free survival (EFS, DFS, PFS). Secondary outcomes were major pathologic response (MPR), overall survival (OS), and safety. Subgroup analyses of EFS/ DFS/ PFS included histology, smoking status, and PDL-1 status. Pooled hazard ratios (HR), odds ratios (OR) and risk ratios (RR) were meta-analyzed using the generic variance, Peto and Mantel-Haenszel methods as appropriate. Random effect models were used to compute pooled estimates. 3926 patients across five neoadjuvant and two adjuvant trials were included. Neoadjuvant ICI improved pCR fivefold compared to chemotherapy alone (OR 5.35; 95% CI, 4.02 - 7.13). Both neo- and adjuvant use of ICI decreased recurrence risk by 34% (HR 0.66; 95% CI, 0.54 - 0.81). Two-year OS improved with adding either neo- or adjuvant ICI (RR 0.73; 95% CI, 0.58 - 0.92) with a trend towards better median OS (HR 0.76; 95% CI, 0.57 - 1.02). Neoadjuvant ICI improved MPR fourfold vs. chemotherapy (OR = 3.91; 95%, CI 2.90 - 5.28). In subgroup analyses, those with non-squamous NSCLC, ever smokers, and tumors with PD-L1>=1% seem to derive a greater benefit from ICI. Neo/Adj ICI increased immune-related adverse effects risk threefold (RR = 3.36; 95% CI, 2.11 - 5.36), with an increase in grade 3 treatment-related toxicity (RR = 1.28; 95% CI, 0.93 - 1.78). Based on preliminary data, adding Neo/Adj ICI improves recurrence rate in resectable NSCLC with a trend towards improved OS. Safety signals were consistent with historical data. Further subgroup evaluations may help to identify suitable population for either approach. [ABSTRACT FROM AUTHOR]

Patients with interstitial lung disease (ILD) who develop lung cancer represent a unique challenge, as they are at a higher risk for serious toxicity from surgery, radiotherapy, and many systemic therapies. The aim of this study is to provide an up-to-date analysis on toxicities and outcomes associated with definitive radiotherapy in patients with ILD and early-stage non-small cell lung cancer (ES-NSCLC). We performed a systematic review in accordance with PRISMA guidelines. The PubMed (MEDLINE), EMBASE, and Cochrane Library databases were searched from inception until March 2024. Studies that included patients who underwent definitive radiotherapy alone for ES-NSCLC were included. All forms of radiotherapy, including proton and carbon ion therapy were included. Data including treatment-related toxicity, local control rates, and overall survival were collected and analyzed. Of the 3096 records reviewed, 24 studies were included for full data abstraction, with a minority (n = 4) being prospective. In total, 705 patients with stage 1-2 NSCLC were included, including both surgical and non-surgical candidates. Seventeen studies utilized photon-based radiotherapy (XRT), 4 carbon ion radiotherapy (CIRT), and 3 proton beam therapy (PBT), with each modality contributing to 81% (n = 574), 13% (n = 90), and 6% (n = 41) of included patients, respectively. Prescribed doses in BED10 ranged from 43 Gy to 180 Gy for XRT, and up to 300 Gy (RBE) for CIRT. Reporting of ILD subtype, severity, and pulmonary function testing were variable. Idiopathic pulmonary fibrosis accounted for 21% (n = 147) of patients, while a specific subtype was not reported for 71% (n = 502) of patients. Within the 11 studies reporting severity data, the majority of patients (65%) had mild ILD as defined by authors, while 26% and 9% had moderate and severe ILD, respectively. Eight studies reported median forced vital capacities ranging from 82-97% of predicted, and 5 reported median diffusing capacities for carbon monoxide ranging from 42-56% of predicted. The prevalence of severe (grade 3-5) treatment-related respiratory toxicity was 16.7% for XRT, 12.2% for CIRT, and 9.7% for PBT, while treatment-related mortality was 9.6% for XRT, 0% for CIRT, and 2.4% for PBT. The most commonly reported risk factor for respiratory toxicity (n = 6) was higher volume of lung receiving at least 5 Gy (V5), with two studies reporting cutoffs of 11.2% and 18%. Estimated local control at 3-years was 75.9%. Estimated overall survival at 3-years was 44.3%, with a median of 30.6 months. There is a high risk of treatment-related toxicity and mortality for patients with ILD who receive definitive radiotherapy for treatment of ES-NSCLC. All treatment modalities should be carefully considered, including the option of ongoing surveillance without treatment. Future studies would benefit from consistent reporting of ILD details, which may help in risk stratification in this challenging clinical scenario. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging-guided stereotactic ablative radiotherapy (MRgSABR) is postulated to further improve the therapeutic ratio of stereotactic radiotherapy by increasing the certainty of dose delivery. As early phase data on MRgSABR have rapidly accumulated, we systematically reviewed the existing literature to summarize the clinical outcomes, toxicity and patient-reported outcomes following MRgSABR. This systematic review was conducted in accordance with consensus guidelines (PROSPERO: CRD42021277584). The PubMed, Embase, and Cochrane Library databases were queried from January 2014 to August 2021. Studies in the English language that evaluated the local control (LC), overall survival (OS), clinician-reported toxicity or patient-reported quality of life outcomes of MRgSABR were included. Reviews or guidelines that did not contribute new results, studies with <=3 total patients, and studies where MRgSABR results could not be disaggregated from radiotherapy using non-MR platforms were excluded. Results were summarized using medians and ranges. We reviewed 849 studies, with 34 (1148 patients) meeting all inclusion criteria. Most studies (56%) were retrospective in nature, with the remaining being prospective single-arm studies. Median follow-up ranged from 4 to 25 months. Liver, prostate, and pancreas were the most common sites for MRgSABR studies. LC was 57-96% (median: 88%) at 1 year and 59-100% (median: 80%) at 2 years after liver MRgSABR (11 studies, 199 patients). OS post-liver MRgSABR was 69-93% (median: 80%) at 1 year and 46-60% (median: 51%) at 2 years. Grade 3 toxicity was 0-8% and no grade 4+ toxicity was reported for the liver. For prostate MRgSABR (6 studies, 282 patients), biochemical control was 75-100% (median: 97%) at a median follow-up of 6 to 12 months. Grade 3+ toxicity was 0-2% and patients reported temporarily increased urinary symptoms during prostate MRgSABR that resolved after treatment. For pancreatic MRgSABR (6 studies, 304 patients), LC was 57-95% (median: 86%) at 1 year and 59-83% (median: 77%) at 2 years. OS was 59-82% (median: 69%) at 1 year and 38-52% (median: 45%) at 2 years after pancreatic MRgSABR. The risk of acute grade 3+ toxicity was 0-4% and the risk of late grade 3+ toxicity was 3-13% following pancreatic MRgSABR. Remaining studies that reported on a variety of treatment sites showed good LC of 72-96% at 1 year (median: 92%). Grade 3+ toxicity was <=5% except for lung (8-20%) and head and neck MRgSABR (43%). Early data on MRgSABR indicate good LC and tolerability across multiple clinical scenarios, though noticeable toxicity was observed in certain treatment sites. Prospective comparative clinical trials are needed to quantify the improvement in clinical outcomes with MRgSABR relative to non-MR-guided radiotherapy technologies. [ABSTRACT FROM AUTHOR]

The aim of this study was to comprehensively review all studies examining clinical outcomes of proton therapy for craniospinal irradiation of medulloblastoma, to determine whether theoretical dosimetric advantages of proton therapy have translated into superior clinical outcomes, including survival and toxicities. We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the PubMed (Medline), EMBASE, and Cochrane Library databases (inception to December 2021). The study was registered with PROSPERO, CRD42022302455. Articles in the English language reporting on clinical outcomes of pediatric and/or adult medulloblastoma patients treated with proton therapy were included. Two independent authors screened all titles/abstracts, reviewed full texts and extracted relevant data, with discrepancies resolved by consensus. Individual study quality was scored using Newcastle Ottawa Scale and overall evidence base by GRADE scale. Thirty-five studies were included, representing 629 unique patients. Publication dates ranged from 2011 to 2021, with the majority (n=32) from the United States. None of the studies were randomized, 12 were comparative, 9 were prospective, 3 mixed and 22 retrospective. Average mean/median follow up was 5.0 years (range = 4 weeks to 12.6 years). The majority of studies (n=19) reported on treatment with passive scatter proton beams exclusively. Average study quality score was 6.08 out of 9 (SD 0.688, median 5). Seven studies scored ≥8/9 on the Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%) and reduced acute toxicities (including myelosuppression, esophagitis, diarrhea, weight loss and nausea/vomiting) in patients treated with protons compared to photons. The 10-year cumulative incidence of secondary malignancy is also lower for proton cohorts (2.1-4.9% vs 8%), but did not reach statistical significance in any individual study. Overall survival (10-yr) (85.3-86.9% for standard-risk disease), progression-free survival (10-yr), patterns of failure, and other endocrine outcomes such as incidence of GH deficiency, adrenal insufficiency and precocious puberty were similar to those reported for photon therapy. Quality of life, ototoxicity and incidence of CNS injury were also found to be comparable between proton and photon cohorts, albeit with lower quality of evidence. Overall, quality of evidence was most robust in the domains of intellectual outcomes, endocrinopathies and acute toxicity. Moderate grade evidence supports proton beam therapy as a preferred treatment for craniospinal irradiation of medulloblastoma based on equivalent disease outcomes and comparable-to-improved toxicity versus photon beam radiotherapy. [ABSTRACT FROM AUTHOR]

Non-inferiority clinical trials are used to investigate whether a new treatment is not worse than a control by an acceptable amount. These new treatments can be more convenient, cost-effective, or tolerable than the standard of care. Although the frequency of this trial design is increasing, the consistency of reporting and interpretation of these trials can vary. The aim of this systematic review was to assess the methodologic quality of non-inferiority radiotherapy clinical trials. A literature search of PubMed, EMBASE and Cochrane databases of randomized controlled radiotherapy trials with non-inferiority hypotheses published in English between January 2000 and July 2021 was performed by an information scientist. Exclusion criteria included study protocols, and follow-up or interim analyses. Records were screened and full texts were reviewed by two authors with discrepancies settled by a third reviewer or by consensus. Descriptive statistics pertaining to study size, primary cancer type, type of comparison, endpoint, and statistical measures were performed. This review was prospectively registered on PROSPERO: CRD42021270644. Of 260 records identified on initial search, 44 (17%) trials were included after full-text review. The mean number of participants was 876 (IQR: 216.25–912.5). All were published after 2004, and open label. Four (9%) trials were funded by industry. The most common primary cancer type was breast (n=10, 23%). Most studies (n=37, 84%) had 2 treatment arms. The most common types of interventions included altered radiation fractionation (n=13, 30%) and changes to systemic therapy agents (n=10, 23%). Six (14%) studies compared radiation to another treatment modality (e.g., surgery, radiofrequency ablation), and 3 (7%) studies examined the omission of radiation. The most common primary endpoints were progression-free survival (n=12, 27%) and local/regional control (n=12, 27%). Forty (91%) studies reported the non-inferiority margin, and only 5 (11%) studies provided a statistical rationale for the margin. The median non-inferiority margin was 10% (IQR: 5–10%). Sample size calculation was reported in 42 (95%) studies, and 42 (95%) studies reported confidence intervals of the primary endpoint. Both intention-to-treat and per protocol analyses were reported in the majority (52%) of studies. In 23 (52%) trials, a non-inferiority claim of the primary endpoint was reached. Clinical trials with a non-inferiority design are relatively uncommon in radiation oncology, and have been used for variable types of comparisons and primary endpoints. Standardization of required data to report and statistical methodology would be helpful to ensure proper interpretation of trial results. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Collagen vascular disease (CVD) is considered a relative contra-indication to radiotherapy. We sought to determine rates of acute and late radiotherapy-associated toxicity in patients with CVD compared to matched controls.Materials/methods: A systematic review was performed following PRISMA guidelines. PubMed was searched for articles from inception to February 2021. Search terms included collagen vascular disease and subtypes; radiotherapy; and cancer. Eligible studies included radiotherapy-associated toxicity rates for at least 10 patients with CVD and their matched controls. Data abstracted included number of patients with CVD; number of controls; median follow-up; treatment period; anatomic sites treated; types of CVD; acute toxicity and late toxicity. Primary endpoints were acute and late grade 3 or higher (3+) toxicity. Random effects meta-analyses of acute and late grade 3+ toxicity were performed using Comprehensive Meta-analysis software for patients with any CVD and their matched controls; patients with scleroderma and their matched controls; and patients with Lupus and their matched controls.Results: The search strategy identified 3573 studies. 17 articles were selected for full-text review and 7 were included for analysis for the primary endpoints. Patients received radiotherapy between 1964 and 2016. 353 patients with CVD were matched to 617 controls, including 19 patients with scleroderma matched to 40 controls and 48 patients with Lupus matched to 82 controls. The most common sites treated were head and neck (31%), breast (29%), and pelvis (11%). Criteria for propensity score included: age, sex, cancer diagnosis, radiotherapy technique, radiotherapy dose, year of radiotherapy and anatomical site of treatment. Patients with CVD had an increased rate of acute grade 3+ toxicity compared to controls (15% vs 9%, P < 0.01, OR = 2.0) and a trend toward an increased rate of late grade 3+ toxicity (11% vs 6%, P = 0.05, OR = 1.7). Patients with scleroderma had an especially high acute grade 3+ toxicity rate compared to controls (25% vs 6%, P = 0.03, OR = 4.1). There was no significant difference in late grade 3+ toxicity between scleroderma patients and their matched controls, and no significant difference in acute or late grade 3+ toxicity between Lupus patients and their matched controls. 5 patients with CVD and no matched controls had treatment-related death.Conclusion: Patients with CVD have a higher rate of acute grade 3+ radiotherapy toxicity compared to matched controls. [ABSTRACT FROM AUTHOR]

Our purpose was to provide an understanding of current functional lung imaging (FLI) techniques and their potential to improve dosimetry and outcomes for patients with lung cancer receiving radiation therapy (RT). Excerpta Medica dataBASE (EMBASE), PubMed, and Cochrane Library were searched from 1990 until April 2023. Articles were included if they reported on FLI in one of: techniques, incorporation into RT planning for lung cancer, or quantification of RT-related outcomes for patients with lung cancer. Studies involving all RT modalities, including stereotactic body RT and particle therapy, were included. Meta-analyses were conducted to investigate differences in dose-function parameters between anatomic and functional RT planning techniques, as well as to investigate correlations of dose-function parameters with grade 2+ radiation pneumonitis (RP). One hundred seventy-eight studies were included in the narrative synthesis. We report on FLI modalities, dose-response quantification, functional lung (FL) definitions, FL avoidance techniques, and correlations between FL irradiation and toxicity. Meta-analysis results show that FL avoidance planning gives statistically significant absolute reductions of 3.22% to the fraction of well-ventilated lung receiving 20 Gy or more, 3.52% to the fraction of well-perfused lung receiving 20 Gy or more, 1.3 Gy to the mean dose to the well-ventilated lung, and 2.41 Gy to the mean dose to the well-perfused lung. Increases in the threshold value for defining FL are associated with decreases in functional parameters. For intensity modulated RT and volumetric modulated arc therapy, avoidance planning results in a 13% rate of grade 2+ RP, which is reduced compared with results from conventional planning cohorts. A trend of increased predictive ability for grade 2+ RP was seen in models using FL information but was not statistically significant. FLI shows promise as a method to spare FL during thoracic RT, but interventional trials related to FL avoidance planning are sparse. Such trials are critical to understanding the effect of FL avoidance planning on toxicity reduction and patient outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 I 2 ., 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 %, I 2  = 19 %), 98 % (95 %CI: 96-99 %, I 2  = 8 %), and 94 % (95 %CI: 90-97 %, I 2  = 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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RG: institutional grant funding- Astellas, TerSera. Honoraria: Bayer, Tolmar, Knight, TerSera. SR: Institutional grant funding – Astra Zeneca, Knight therapeutics. Honoraria – Bayer, Astra Zeneca, Tersera, Sanofi, Verity pharma., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The treatment landscape of genitourinary cancers has significantly evolved over the past few years. Renal cell carcinoma, bladder cancer, and prostate cancer are the most common genitourinary malignancies. Recent advancements have produced new targeted therapies, particularly antibody-drug conjugates (ADCs), due to a better understanding of the underlying oncogenic factors and molecular mechanisms involved. ADCs function as a 'drug delivery into the tumor' system. They are composed of an antigen-directed antibody linked to a cytotoxic drug that releases cytotoxic components after binding to the tumor cell's surface antigen. ADCs have been proven to be extremely promising in the treatment of several cancer types. For GU cancers, this novel treatment has only benefited patients with metastatic urothelial cancer (mUC). The rest of the GU cancer paradigm does not have any FDA-approved ADC treatment options available yet. In this study, we have thoroughly completed a narrative review of the current literature and summarized preclinical studies and clinical trials that evaluated the utility, activity, and toxicity of ADCs in GU cancers, the prospects of ADC development, and the ongoing clinical trials. Prospective clinical trials, retrospective studies, case reports, and scoping reviews were included.

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Radiation therapy is used frequently for patients with prostate cancer. Dose escalation to intraprostatic lesions (IPLs) has been shown to improve oncologic outcomes, without increasing toxicity. Both multiparametric MRI (mpMRI) and PSMA PET can be used to identify IPLs., Materials and Methods: A systematic review was conducted to determine the ability of mpMRI, PSMA PET and their combination to detect IPLs prior to radical prostatectomy (RP) as correlated with the histology. Trials included patients that had mpMRI, PSMA PET, or both, prior to RP. The quality of the histopathological-radiological co-registration was assessed as high or low for each study. Recorded outcomes include sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A meta-analysis was conducted using a bivariate model to determine the pooled sensitivity and specificity for each imaging modality. This systematic review was registered through PROSPERO (CRD42023389092)., Results: Altogether, 42 studies were included in the systematic review. Of these, 20 could be included in the meta-analysis. The pooled sensitivity (95 % CI), specificity (95 % CI) and AUROC for mpMRI (n = 13 studies) were 64.7 % (50.2 % - 76.9 %), 86.4 % (79.7 % - 91.1 %), and 0.852; the pooled outcomes for PSMA PET (n = 12) were 75.7 % (64.0 % - 84.5 %), 87.1 % (80.2 % - 91.9 %), and 0.889; for their combination (n = 5), the pooled outcomes were 70.3 % (64.1 % - 75.9 %), 81.9 % (71.9 % - 88.8 %), and 0.796. When reviewing studies with a high-quality histopathological-radiological co-registration, IPL delineation recommendations varied by study and the imaging modality used., Conclusion: All of mpMRI, PSMA PET or their combination were found to have very good diagnostic outcomes for detecting IPLs. Recommendations for delineating IPLs varied based on the imaging modalities used and between research groups. Consensus guidelines for IPL delineation would help with creating consistency for focal boost radiation treatments in future studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Glenn Bauman is Primary Investigator on the OICR funded trial ARGOS/CLIMBER that is examining the use of hybrid PSMA PET/MRI for dose escalation in high intermediate and high risk prostate cancer. Dr. Bauman also leads other clinical trials examining the use of PSMA PET/CT in the management of men with prostate cancer that are funded through Ontario Health-Cancer Care Ontario. All other authors declare that they have no know competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Medical care for cancer is increasingly directed by genomic laboratory testing for alterations in the tumor genome that are significant for diagnosis, prognosis and therapy. Uniquely in medicine, providers must search the biomedical literature for each patient to determine the clinical significance of these alterations. Access to published scientific literature is frequently subject to high fees, with access limited to institutional subscriptions. We sought to investigate the degree to which the scientific literature is accessible to clinical cancer genomics providers, and the potential role of university and hospital system libraries in information access for cancer care., Methods: We identified 265 journals that were accessed during the interpretation and reporting of clinical test results from 1,842 cancer patients at the University Health Network (Toronto, Canada). We determined the degree of open access for this set of clinically important literature, and for any journals not available through open access we surveyed subscription access at seven academic hospital systems and at their affiliated universities., Results: This study found that nearly half (116/265) of journals have open access mandates that make articles freely available within one year of release. For the remaining subscription access journals, universities provided a uniformly high level of access, but access available through hospital system collections varied widely., Conclusion: This study highlights the importance of different modes of access to the use of the scientific literature in clinical practice and points to challenges that must be overcome as genomic medicine grows in scale and complexity., (Copyright © 2023 Schnell D'Souza, Gregory Downs, Shawn Hendrikx, Rouhi Fazelzad, Gabriel Boldt, Karen Burns, Darlene Chapman, Declan Dawes, Antonia Giannarakos, Lori Anne Oja, Risa Schorr, Maureen Babb, Amada Hodgson, Jessica McEwan, Pamela Jacobs, Tracy Stockley, Tim Tripp, Ian King.)

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., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways have demonstrated promising results for treatment of advanced non-small cell lung cancer. We conducted a systematic review and meta-analysis to assess the efficacy and toxicity of the combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for patients with advanced non-small cell lung cancer harboring activating EGFR mutations, in comparison to EGFR TKIs alone. The electronic databases were searched for relevant randomized trials between 2000 and 2022. The primary endpoints were overall survival (OS) and progression-free survival. Secondary endpoints included objective response rate (ORR), disease control rate, and grade ≥3 adverse events (AEs). The pooled hazard ratios (HR) and odds ratios were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. A total of 1528 patients from 8 trials were evaluated for analyses. The combination treatment decreased the risk of disease progression by 37% (HR=0.63; 95% CI, 0.56 to 0.72) but had no added benefit on OS compared with EGFR inhibition alone (HR=0.90; 95% CI, 0.76 to 1.05). There was no significant difference in objective response rate or disease control rate between treatments. There was a significantly increased number of AEs reported in the dual treatment arm (odds ratio=3.02; 95% CI, 1.71 to 5.31), with proteinuria and hypertension being the most significantly increased AEs. This meta-analysis suggests combined inhibition of EGFR and VEGF pathways significantly improves progression-free survival, with no OS benefit, and increases AEs. Mature OS data are needed along with results from more trials exploring this strategy with third-generation EGFR TKIs to strengthen these results., Competing Interests: D.B. has provided advisory board participation or received honoraria from Amgen Canada, Bristol-Myers-Squibb, AstraZeneca, and Takeda. J.R. has provided advisory board participation or received honoraria from Roche, Novartis, Merck, Lilly, and AstraZeneca. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)