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Background & Aims: Transcatheter arterial chemoembolisation (TACE) is recommended for patients with hepatocellular carcinoma devoid of macrovascular invasion or extrahepatic spread but not eligible for curative therapies. We compared the efficacy and safety of the combination of a single TACE and external conformal radiotherapy (CRT) vs . classical TACE., Methods: TACERTE was an open-labelled, randomised controlled trial with a 1:1 allocation rate to two or three TACE (arm A) or one TACE + CRT (arm B). Participants had a mean age of 70 years, and 86% were male. The aetiology was alcohol in 85%. The primary endpoint was liver progression-free survival (PFS) in the intention-to-treat population. The typical CRT schedule was 54 Gy in 18 sessions of 3 Gy., Results: Of the 120 participants randomised, 64 were in arm A and 56 in arm B; 100 participants underwent the planned schedule and defined the 'per-protocol' group. In intention-to-treat participants, the liver PFS at 12 and 18 months were 59% and 19% in arm A and 61% and 36% in arm B (hazard ratio [HR] 0.69; 95% CI 0.40-1.18; p  = 0.17), respectively. In the per-protocol population, treated liver PFS tended to be better in arm B (HR 0.61; 95% CI 0.34-1.06; p  = 0.081) than in arm A. Liver-related grade III-IV adverse events were more frequent in arm B than in arm A. Median overall survival reached 30 months (95% CI 23-35) in arm A and 22 months (95% CI 15.7-26.2) in arm B., Conclusions: Although TACE + CRT tended to improve local control, this first Western randomised controlled trial showed that the combined strategy failed to increase PFS or overall survival and led more frequently to liver-related adverse effects., Impact and Implications: Hepatocellular carcinoma is frequently treated by arterial embolisation of the tumour and more recently by external radiotherapy. We tried to determine whether combination of the two treatments (irradiation after embolisation) might produce interesting results. Our results in this prospective randomised study were not able to demonstrate a beneficial effect of combining embolisation and irradiation in these patients. On the contrary, we observed more adverse effects with the combined treatment., Clinical Trials Registration: NCT01300143., Competing Interests: CF, LC, IA, XM, ER, CP, LM, FO, YT, JG, HR, JE, AR, PH, JFB, ENK, DA, AGP, EF-P, and HA did not receive any grants or funding. P Merle reports grants or funding from Roche, AstraZeneca, MSD, Eisai, Bayer, and Ipsen. P Mathurin reports grants or funding from Ipsen, Eisai, Abbvie, Sanofi, Gilead Sciences, Pfizer, Evive Biotech, Novo Nordisk, Bayer Healthcare, Surrozen, and Intercept. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Background: Cardiovascular disease (CVD) incidence is higher in men with prostate cancer (PC) than without., Objectives: We describe the rate and correlates of poor cardiovascular risk factor control among men with PC., Methods: We prospectively characterized 2,811 consecutive men (mean age 68 ± 8 years) with PC from 24 sites in Canada, Israel, Brazil, and Australia. We defined poor overall risk factor control as ≥3 of the following: suboptimal low-density lipoprotein cholesterol (>2 mmol/L if Framingham Risk Score [FRS] ≥15 and ≥3.5 mmol/L if FRS <15), current smoker, physical inactivity (<600 MET min/wk), suboptimal blood pressure (BP) (≥140/90 mm Hg if no other risk factors, systolic BP ≥ 120 mm Hg if known CVD or FRS ≥15, and ≥130/80 mm Hg if diabetic), and waist:hip ratio >0.9., Results: Among participants (9% with metastatic PC and 23% with pre-existing CVD), 99% had ≥1 uncontrolled cardiovascular risk factor, and 51% had poor overall risk factor control. Not taking a statin (odds ratio [OR]: 2.55; 95% CI: 2.00-3.26), physical frailty (OR: 2.37; 95% CI: 1.51-3.71), need for BP drugs (OR: 2.36; 95% CI: 1.84-3.03), and age (OR per 10-year increase: 1.34; 95% CI: 1.14-1.59) were associated with poor overall risk factor control after adjustment for education, PC characteristics, androgen deprivation therapy, depression, and Eastern Cooperative Oncology Group functional status., Conclusions: Poor control of modifiable cardiovascular risk factors is common in men with PC, highlighting the large gap in care and the need for improved interventions to optimize cardiovascular risk management in this population., Competing Interests: RADICAL-PC is an investigator-initiated study that is funded by Prostate Cancer Canada (grant CT2015-01); the Movember Foundation, Hamilton Health Sciences (Research Strategic Initiative Program); and the Canadian Cancer Society (grant 706677). The funders of the study had no role in design of the study, analysis, interpretation, writing of the manuscript, and in the decision to publish the results. Dr Klimis is supported by an AFP Fellowship Award, Department of Cardiology, McMaster University. Dr Pinthus has served on advisory boards for Ferring Pharmaceuticals and Myovant Sciences; and has received research grant from Ferring Pharmaceuticals. Dr Duceppe has received investigator-initiated research grants from Roche Diagnostics and Abbott Laboratories; and has received lecture fees and honoraria for participation in advisory board meetings with Roche Diagnostics. Dr Siemens has been involved in clinical trials with Merck, Pfizer, Astellas, and Bayer. Dr Lavallee is on the advisory board for Sanofi, Astellas, Janssen, and Knight. Dr Gopaul has received personal fees outside the submitted manuscript from AstraZeneca, TerSera, Bayer, Ferring, and Abvie. Dr Hanna is on the advisory board for and has received honorarium and research support from Astellas, Bayer, Merck, Tolmar, Sanofi, and Abbvie. Dr Iakobishvili consults and lectures for Bayer, Pfizer, Boehringer Ingelheim, Novo Nordisk, Medtronic, Sanofi Adventist, and AstraZeneca. Dr Selvanayagam has received research grant support from Biotronik, Bayer, Sanofi, Actelion, and Novartis; is on the advisory board for Sanofi, Faraday, and Recardio; and is on the speaker bureau for AstraZeneca, Boehringer-Ingelheim, Novartis, Abbot, Bayer, Sanofi, Biotronik, Circle CVI, and Takeda. Dr Leong has served on advisory boards for Ferring Pharmaceuticals, Myovant Sciences, and Tolmar; reports speaker’s honoraria from Abbvie; and is supported by the Clive Kearon Career Award, Department of Medicine, McMaster University. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background & Aims: We elucidated the clinical and immunologic implications of serum IL-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev)., Methods: We prospectively enrolled 165 patients with unresectable HCC (discovery cohort: 84 patients from three centres; validation cohort: 81 patients from one centre). Baseline blood samples were analysed using a flow cytometric bead array. The tumour immune microenvironment was analysed using RNA sequencing., Results: In the discovery cohort, clinical benefit 6 months (CB 6m ) was defined as complete or partial response, or stable disease for ≥6 months. Among various blood-based biomarkers, serum IL-6 levels were significantly higher in participants without CB 6m than in those with CB 6m (mean 11.56 vs . 5.05 pg/ml, p  = 0.02). Using maximally selected rank statistics, the optimal cut-off value for high IL-6 was determined as 18.49 pg/ml, and 15.2% of participants were found to have high IL-6 levels at baseline. In both the discovery and validation cohorts, participants with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev treatment compared with those with low baseline IL-6 levels. In multivariable Cox regression analysis, the clinical implications of high IL-6 levels persisted, even after adjusting for various confounding factors. Participants with high IL-6 levels showed reduced interferon-γ and tumour necrosis factor-α secretion from CD8 + T cells. Moreover, excess IL-6 suppressed cytokine production and proliferation of CD8 + T cells. Finally, participants with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumour microenvironment., Conclusions: High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment., Impact and Implications: Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab., Competing Interests: HJC has a consulting or advisory role at Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, Sillajen, Menarini, and GreenCross Cell, and has received research grants from Roche, Dong-A ST, and Boryung Pharmaceuticals. CK has a consulting or advisory role at Roche, ONO, MSD, BMS, Oncocross, Virocure, Sillajen, and Panolos Biosciences, and has received research grants from Boryung Pharmaceuticals, Oncocross, Sillajen, and Virocure. JC has a consulting or advisory role at Roche, MSD China, Eisai, and Servier, and has received research grants from Bayer. VEG is an employee of F. Hoffmann-La Roche Ltd. and has stock options from F. Hoffmann-La Roche Ltd. The other authors have no potential conflicts of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background & Aims: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study., Methods: We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes., Results: The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p  = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 ( p = 0.0018), presence of ascites ( p = 0.0152), right-sided tumours ( p = 0.0002), the presence of portal vein thrombosis ( p = 0.0378) and main portal vein thrombosis ( p = 0.0028), ALBI grade 2 ( p = 0.0043) and 3 ( p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events., Conclusions: This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes., Impact and Implications: Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE., Clinical Trial Number: NCT02305459., Competing Interests: Frank Kolligs participated on a data safety monitoring or advisory board of Bayer, MSD, and Roche. Dirk Arnold received consulting fees and honoraria for presentations and lectures and travel support from Boston Scientific and Terumo, is on the guidelines committee of the European Society for Medical Oncology, and supported oncopolicy manuscripts for the European Cancer Organisation. Rita Golfieri participated on a Data Safety Monitoring Board or Advisory Board and received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Roche, Guerbet and Sirtex. Maciej Pech received grants or contracts and honoraria from lectures from Sirtex and Bayer. Maxime Ronot received honoraria for lectures from GE Healthcare, Ipsen, Canon-Toshiba, Alexion Pharmaceuticals, Guerbet, and Sirtex. Bruno Sangro received grants or contracts from Sirtex and BMS, consulting fees from Adaptimmune, Astra Zeneca, Bayer, BMS, Boston Scientific, Eisai, Eli Lilly, Incyte, Ipsen, Roche, Sirtex Medical, Terumo; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca, Bayer, BMS, Eisai, Incyte, Ipsen, Roche, Sirtex Medical; Participation on a data safety monitoring board or advisory board from Adaptimmune, Astra Zeneca, Bayer, BMS, Boston Scientific, Eisai, Eli Lilly, Incyte, Ipsen, Roche, Sirtex Medical, Terumo, and has a leadership or fiduciary role in the International Liver Cancer Association. Geert Maleux received honoraria for speaker’s bureau from Sirtex Medical and operated as proctor for Sirtex. Bora Peynircioglu, Thomas Pfammatter, Niklaus Schaefer, Graham Munneke, Helena Pereira, Bleranda Zeka, Niels de Jong and Thomas Helmberger had nothing to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Background: Performance status (PS) is a reliable prognostic tool for overall survival in patients with cancer-associated pulmonary embolism (PE). However, its association with venous thromboembolism (VTE) recurrence and bleeding remains unclear., Objectives: The aim of this study was to investigate whether PS at the time of PE diagnosis and its course during follow-up are linked to VTE-related outcomes., Methods: In this post hoc analysis of the Hokusai-VTE Cancer study, multivariable survival analysis was used to examine the association of PS with anticoagulation discontinuation and the composite primary outcome of VTE recurrence or major bleeding in patients with cancer-associated PE. PS was assessed using the Eastern Cooperative Oncology Group (ECOG) scale at baseline and at predefined study follow-up visits., Results: Overall, 652 patients with cancer-associated PE were included. During 12-month follow-up, PS worsened in 317 of 642 patients (49.4%) with complete ECOG data at the end of follow-up. Those with worse ECOG values over follow-up were more likely to discontinue anticoagulation for any reason apart from death (adjusted HR: 1.59; 95% CI: 1.31-1.93). The composite primary outcome occurred in 57 of 500 patients with baseline ECOG status 0 or 1 and in 32 of 152 patients with ECOG status 2 (cumulative incidence at 12 months 10.7% [95% CI: 8.2%-13.9%] vs 14.4% [95% CI: 9.7%-21.3%]). Worse ECOG values during follow-up were associated with greater risk for the composite outcome (adjusted HR: 2.13; 95% CI: 1.24-3.67)., Conclusions: ECOG PS is a valuable indicator for predicting VTE-related outcomes and may inform decision making regarding anticoagulation during follow-up in patients with cancer-associated PE., Competing Interests: This study was supported by an unrestricted grant from Daiichi Sankyo (grant DSE-DE-CV-20001). Dr Barco has received lecture and consulting fees from Bayer HealthCare, Concept Medical, BTG Pharmaceuticals, Inari Medical, Boston Scientific, and LeoPharma; has received institutional grants from Boston Scientific, Bentley, Bayer HealthCare, Inari Medical, Medtronic, Concept Medical, Bard, and Sanofi; and has received financial support for travel and congress costs from Daiichi Sankyo, BTG Pharmaceuticals, and Bayer HealthCare, outside the submitted work. Dr Konstantinides has received institutional grants and personal lecture and advisory fees from Bayer, Daiichi Sankyo, and Boston Scientific; has received institutional grants from Inari Medical; and has received personal lecture and advisory fees from Merck Sharpe & Dohme and Bristol Myers Squibb/Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

We conducted a retrospective tumor tissue analysis as part of the BRIM3 trial to evaluate the theragnostic significance of tumor-infiltrating lymphocytes (TILs) and melanoma cell proliferation. Using manual semi-quantitative analyses, we assessed the density of TILs by pathology review of tissue sections stained with hematoxylin and eosin (H&E TIL score) and by immunohistochemistry (IHC) with an anti–CD8 antibody (CD8 TIL score); also, the melanoma cell proliferation by IHC with an anti–Ki67 antibody. Three hundred and fifty-three, 280, and 172 patients' tumor tissue samples were available for H&E, CD8, and Ki67 IHC analysis, respectively. There was no association between high (2+, 3+) peritumoral and intratumoral H&E and/or TIL CD8 score or high Ki67 proliferation index (>15%) with serum LDH level and stage IV melanoma. Neither high Ki67 proliferation, nor high peritumoral and/or intratumoral TIL score was significantly associated with objective antitumor response in any treatment arm. High intratumoral and high peritumoral CD8 TIL score was significantly associated with progression-free survival (PFS) only in DTIC-treated patients (P = 0.002 and 0.037, respectively); in vemurafenib-treated patients, high intratumoral and/or peritumoral CD8 TIL score was not significant (log-rank P = 0.053 and 0.062, respectively). Nevertheless, a high peritumoral CD8 TIL score was a significant predictor of PFS and overall survival after adjustment for age, sex, serum LDH, ECOG performance status, and treatment arm in a Cox regression model. Vemurafenib does not only benefit patients bearing brisk TILs; even vemurafenib-treated patients with absent and/or non–brisk TILs tend to have longer PFS compared to DTIC-treated patients with brisk TILs. High peritumoral CD8 TIL score is a favorable prognostic factor independent of well-established AJCC staging factors. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N -terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome. A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits. A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk. Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier GmbH.)

Objective: To determine how postsurgical remote patient monitoring (RPM) influences readmissions and emergency visits within 30 days of discharge after operation and to understand patient and surgeon perspectives on postsurgical RPM., Patients and Methods: This study was conducted at a US tertiary academic medical center between April 1, 2021, and December 31, 2021. This mixed-methods evaluation included a randomized controlled trial evaluation of RPM after operation and a qualitative assessment of patients' and surgeons' perceptions of RPM's acceptability, feasibility, and effectiveness., Results: A total of 292 patients participated in the RPM trial, and 147 were assigned to the RPM intervention. Despite a good balance between the groups, results indicated no difference in primary or secondary outcomes between the intervention and control groups. The qualitative component included 11 patients and 9 surgeons. The overarching theme for patients was that the program brought them peace of mind. Other main themes included technological issues and perceived benefits of the RPM platform. The major themes for surgeons included identifying the best patients to receive postsurgical RPM, actionable data collection and use, and improvements in data collection needed., Conclusion: Although quantitative results indicate no difference between the groups, postsurgical RPM appears well-accepted from the patient's perspective. However, technological issues could eliminate the benefits. Hospitals seeking to implement similar programs should carefully evaluate which populations to use the program in and seek to collect actionable data., (© 2022 The Authors.)

Background: There is no curative treatment option for patients with unresectable intrahepatic, cholangiocarcinoma (IHC). The aim of this study was to evaluate the efficacy of; radiation segmentectomy/lobectomy using Y90-labeled glass microspheres in patients with; unresectable IHC., Methods: This IRB-approved, single-center study included, 16 patients (age: 67 ± 7.7 years) with IHC who received radiation segmentectomy or lobectomy, treatment using Y90-labeled glass microspheres between May 2009 and October 2019. Radiation, segmentectomy/lobectomy was defined as at least 190 Gy dose delivered into treated liver; volume., Results: The median OS from IHC diagnosis was 22.7 months (95% CI: 13.9-66.1) and from, radioembolization it was 7 months (95% CI: 4.33-54.17). Patients who did not receive, chemotherapy before the radioembolization had significantly longer median OS (26.8 vs. 5.9, months, P  = 0.03). Four patients had >20 months survival after radioembolization, including 2, patients with survival of 42 and 54 months. There was no 30-day mortality and no severe, complications., Conclusion: Radiation segmentectomy/lobectomy is safe with minimal side effects. The median, OS of the study group is modest; however, 4 patients (25%) showed excellent survival. These results suggest a need for a larger study to define the IHC patient group who could, most benefit from this procedure., Competing Interests: The author has none to declare., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We investigated the pharmacokinetics (PK), preliminary clinical results and toxicity of chronomodulated oxaliplatin (OHP) plus 5-fluorouracil (5-FU) without folinic acid (FA) in 13 patients with metastatic colorectal cancer. 5-FU (200 mg/m2/day as 14-day continuous iv infusion for six cycles) plus OHP at increasing doses (25–30–35 mg/m2/day, as 12 h chronomodulated iv infusion on days 1-2-3-4, every 14 days for six cycles) were administered to reach maximum tolerated dose (MTD). At MTD (30 mg/m2/day), a PK study of 5-FU and OHP (in total and ultrafiltered-UF plasma) was performed. 5-FU plasma levels were fairly stable, below that reported in similar studies and closely related to the lack of the most typical 5-FU toxicities. OHP Cmax occurred 7 h after infusion start; a progressive accumulation of free Pt and ultrafiltered Pt (UF-OHP) through cycles 1-6 was noted. A marked difference between total plasma and UF Pt was seen in the elimination phase. OHP plasma clearance decrease was related to Vz (volume of distribution of late elimination phase), whereas in UF-OHP was due to a change in Ke or t1/2. In conclusion, the association of 5-FU with chronomodulated OHP do not seem to influence PK parameters of either drugs. Toxicity was modest/acceptable and clinical efficacy good: preliminary data showed a threshold neurotoxicity at total plasma Pt concentrations >1500 ng/ml and UF plasma Pt concentrations >150 ng/ml. [Copyright &y& Elsevier]

Background: Patients with primary brain tumours (i.e., neuro-oncology patients) lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise - Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness., Methods: Neuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro and other cancer rehabilitation services (including physiatry, physiotherapy, occupational therapy, and exercise physiology). In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes and functional fitness, and objective physical activity tracked across the 12-week program. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching., Conclusion: We are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription., (© 2022 The Authors.)

Aims: Our objective was to determine if preoperative patient-reported assessments are associated with survival after surgery for stabilization of skeletal metastases., Patients and Methods: All patients with metastatic cancer to bone and indications for skeletal stabilization surgery were approached to participate in a prospective cohort study at a tertiary care center from 2012 to 2017. Of the 208 patients who were eligible, 195 (94%) completed the 36-item Short Form Health Survey (SF-36) preoperatively and underwent surgical treatment of skeletal metastases with complete or impending fractures; the sample encompassed a range of cancer diagnoses and included cases of both internal fixation and endoprosthetic replacement. Cox proportional hazards models were used to identify associations between SF-36 scores and survival., Results: In a model adjusted for clinical factors, patients' mental and physical SF-36 component summary scores were significantly associated with survival, as was their SF-36 composite score ( P  = 0.004, P  = 0.015, and P  < 0.001, respectively). Scores in the general health, vitality, and mental health domains were each strongly associated with survival ( P  < 0.001)., Conclusions: Patients' preoperative assessments of their health status are associated with their survival after surgery for skeletal metastases. Patient-reported assessments have the potential to contribute unique information to models that estimate patient survival, as part of efforts to provide optimal, individualized care and make informed decisions about the type and magnitude of surgery for metastatic bone disease that will last the patient's lifetime., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: The optimal treatment for recurrent non-small cell lung cancer (NSCLC) has not been standardized. In this prospective cohort study, we evaluated post-recurrence survival (PRS) after treatment of recurrent NSCLC and identified prognostic factors after recurrence., Methods: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data, such as treatment and survival outcomes, were obtained every 3 months., Results: From 2010 to 2015, 505 cases were enrolled, and 495 cases were analyzed. As initial treatment for recurrence, 263 patients (53%) received chemotherapy, 46 (9%) received chemoradiotherapy, 98 (20%) had definitive radiotherapy, 14 (3%) received palliative radiotherapy, and 31 (6%) underwent surgical resection. The remaining 43 patients (9%) received supportive care. The median PRS and 5-year survival rates for all cases were 30 months and 31.9%, respectively. The median PRS according to the initial treatment was as follows: supportive care, 8 months; palliative radiotherapy, 16 months; definitive radiotherapy, 30 months; chemotherapy, 31 months; chemoradiotherapy, 35 months; and surgery, not reached. A multivariate analysis showed that the age, gender, performance status, histology presence of symptoms, duration from primary surgery to recurrence, and number of recurrent foci were independent prognostic factors for PRS., Conclusions: The PRS of patients with recurrent NSCLC was different depending on the patient's background characteristics and initial treatment for recurrence., (© 2022 The Author(s).)

Background: Clinical practice guidelines recommend the use of bone-targeting agents for preventing skeletal-related events (SREs) among patients with bone metastases from solid tumors. The anti-RANKL monoclonal antibody denosumab is approved for the prevention of SREs in patients with bone metastases from solid tumors. However, real-world data are lacking on the impact of individual risk factors for SREs, specifically in the context of denosumab discontinuation., Purpose: We aim to identify risk factors associated with SRE incidence following denosumab discontinuation using a machine learning approach to help profile patients at a higher risk of developing SREs following discontinuation of denosumab treatment., Methods: Using the Optum PanTher Electronic Health Record repository, patients diagnosed with incident bone metastases from primary solid tumors between January 1, 2007, and September 1, 2019, were evaluated for inclusion in the study. Eligible patients received ≥ 2 consecutive 120 mg denosumab doses on a 4-week (± 14 days) schedule with a minimum follow-up of ≥ 1 year after the last denosumab dose, or an SRE occurring between days 84 and 365 after denosumab discontinuation. Extreme gradient boosting was used to develop an SRE risk prediction model evaluated on a test dataset. Multiple variables associated with patient demographics, comorbidities, laboratory values, treatments, and denosumab exposures were examined as potential factors for SRE risk using Shapley Additive Explanations (SHAP). Univariate analyses on risk factors with the highest importance from pooled and tumor-specific models were also conducted., Results: A total of 1,414 adult cancer patients (breast: 40%, prostate: 30%, lung: 13%, other: 17%) were eligible, of whom 1,133 (80%) were assigned to model training and 281 (20%) to model evaluation. The median age at inclusion was 67 (range, 19-89) years with a median duration of denosumab treatment of 253 (range, 88-2,726) days; 490 (35%) patients experienced ≥ 1 SRE 83 days after denosumab discontinuation. Meaningful model performance was evaluated by an area under the receiver operating curve score of 77% and an F1 score of 62%; model precision was 60%, with 63% sensitivity and 78% specificity. SHAP identified several significant factors for the tumor-agnostic and tumor-specific models that predicted an increased SRE risk following denosumab discontinuation, including prior SREs, shorter denosumab treatment duration, ≥ 4 clinic visits per month with at least one hospitalization (all-cause) event from the baseline period up to discontinuation of denosumab, younger age at bone metastasis, shorter time to denosumab initiation from bone metastasis, and prostate cancer., Conclusion: This analysis showed a higher cumulative number of SREs, prior SREs relative to denosumab initiation, a higher number of hospital visits, and a shorter denosumab treatment duration as significant factors that are associated with an increased SRE risk after discontinuation of denosumab, in both the tumor-agnostic and tumor-specific models. Our machine learning approach to SRE risk factor identification reinforces treatment guidance on the persistent use of denosumab and has the potential to help clinicians better assess a patient's need to continue denosumab treatment and improve patient outcomes., Competing Interests: Dionna Jacobson, Benoit Cadieux, and Basia A. Bachmann, were employees of Amgen. Marko Rehn and Hossam Saad are employees and stockholders of Amgen. Celestia S. Higano – consulting fees: Bayer, Ferring, Clovis Oncology, Blue Earth Diagnostics, Janssen, Hinova, Pfizer, AstraZeneca, Carrick Therapeutics, Novartis, Merck Sharp & Dohme, Astellas Pharma, Myovant Sciences, Genentech, Menarini; contracted research support: Aragon Pharmaceuticals, AstraZeneca, Medivation, Emergent BioSolutions, Bayer, Roche, Astellas Pharma, Clovis Oncology, Ferring Pharmaceuticals, eFFECTOR Therapeutics; ownership interest: CTI BioPharma CORP; honoraria: Astellas Pharma. David H. Henry has nothing to disclose. Alison T. Stopeck – consulting fees: Amgen, AstraZeneca, Athenex, BeiGene, Exact Sciences; contracted research support: Amgen, Genomic Health, AstraZeneca, Seattle Genetics; speaker’s bureau: Genomic Health; honoraria: Amgen., (© 2022 The Authors.)

Background: Numerous studies have shown that improving oral hygiene contributes to a reduction in the risk of postoperative complications in patients with head and neck cancer, cardiac disease, and esophageal cancer. However, the beneficial standard for oral management procedures during the perioperative period has not yet been established. Therefore, our aim was to determine whether or not their innovative oral management intervention contributed to a reduction in postoperative complications in lung cancer., Methods: We performed a retrospective analysis of medical records of patients who underwent lung cancer surgery with lobectomy and pneumonectomy at Kyorin University Hospital. Patients were divided into 2 groups: a perioperative oral management intervention group that underwent lung cancer surgery from April 2016 to March 2018 (n = 164), and a control group without oral management that underwent surgery from April 2014 to March 2016 (n = 199). In particular, our oral management procedure emphasized oral mucosa stimulation to induce saliva discharge as in gum chewing, rather than simply using teeth brushing to reduce oral microbiome. Therefore, our oral management procedure is different from traditional oral care., Results: This study demonstrated that our oral management practice was associated with a decline in the occurrence of postoperative pneumonia (odds ratio, 0.184; 95% CI, 0.042-0.571; P  = .009), postoperative hospital stay duration (β coefficient, -4.272; 95% CI, -6.390 to -2.155; P  < .001) and Clavian-Dindo classification grade II or above (odds ratio, 0.503; 95% CI, 0.298-0.835; P  = .009)., Conclusions: We propose an innovative new strategy using their unique oral management procedure to reduce postoperative complications resulting from pulmonary resection., (© 2022 The Author(s).)

Introduction: The potential of patient symptoms being monitored longitudinally in radiotherapy (RT) is still unexploited. When novel technologies like online adaptive MR-guided radiotherapy (MRgRT) are evaluated, weekly electronic patient-reported outcomes (ePROs) may add knowledge about the symptom trajectory. This study aimed at evaluating feasibility, usability and acceptance of weekly ePRO among patients receiving pelvic radiotherapy., Materials and Methods: In a mixed-methods convergent design, a prospective pilot study enrolled patients referred to pelvic radiotherapy with curative intent. Patients used their own device at home to self-report PRO weekly during and four weeks following radiotherapy and week 8, 12, and 24 (paper-questionnaire as an alternative). Feasibility was extracted from the ePRO software. The Patient Feedback Form and patient interviews were used to explore usability and patient acceptance. Patients were informed that clinicians had no access to PRO responses., Results: In total, 40 patients were included; 32 patients with prostate cancer and 8 with cervical cancer (consent rate 87%), median age 68 (36-76). The majority did digital reporting (93%). 85% of patients responded to ≥80% of the weekly questionnaires with 91% average adherence to weekly completion (60% for follow-up), although lower for patients ≥age 70. Time spent on ePRO (97%) and frequency of reporting (92%) was considered appropriate. Interviews (n = 14) revealed the application was usable and the patients requested real-time feedback from the clinicians., Conclusion: Recruitment for ePRO during radiotherapy was feasible and adherence to weekly self-reporting high. The digital application was usable and weekly frequency and time spent acceptable. Real-time feedback from the clinicians is requested by the patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy & Oncology.)

Background: Preoperative frailty has been associated with adverse postoperative outcomes. Additionally, low testosterone has been associated with physical frailty and cognitive decline. However, the impact of simultaneous frailty and low testosterone on surgical outcomes is understudied., Methods: Preoperative frailty status and testosterone levels were obtained in patients undergoing a diverse range of surgical procedures. Preoperative frailty was evaluated independently and in combination with testosterone through the creation of composite risk groups. Relationships between preoperative frailty and composite risk groups with overall survival were determined using Kaplan-Meier and logistic regression analyses. Bivariate analysis was used to determine the associations between frailty and testosterone status on postoperative complications, length of hospital stay, and readmission rates., Results: Median age of the cohort was 63 years, and the median follow-up time was 105 weeks. Thirty-one patients (23%) were frail, and 36 (27%) had low free testosterone. Bivariate analysis demonstrated a statistically significant relationship between preoperative frailty and overall survival (P = .044). In multivariate analysis, coexisting frailty and low free testosterone were significantly associated with decreased overall survival (hazard ratio 4.93, 95% confidence interval, 1.68-14.46, P = .004)., Conclusion: We observed preoperative frailty, both independently and in combination with low free testosterone levels, to be significantly associated with decreased overall survival across various surgical procedures. Personalizing the surgical risk assessment through the incorporation of preoperative frailty and testosterone status may serve to improve the prognostication of patients undergoing major surgery., (© 2021 The Authors.)

Objectives: This retrospective study investigated prognostic factors in advanced non-small cell lung cancer (NSCLC) with bone-only metastasis, and developed a graded prognostic assessment (GPA) model to estimate patient survival., Methods: The primary endpoint was overall survival. We investigated the patients with advanced NSCLC with bone-only metastasis at the initial diagnosis and diagnosed between 2013 and 2019 in our hospital. A log-rank test and Cox proportional hazards model were used to examine factors. A GPA model was developed in the training set based on the factors that were determined significant according to their hazard ratios and verified by the validation set., Results: We finally included 220 patients for analysis. These patients were divided into two groups, 147 cases for the training cohort and 73 for the validation cohort. The following were significant independent prognostic factors, and were included in the GPA model: smoking; EGFR (epidermal growth factor receptor) sensitive/ALK (anaplastic lymphoma kinase) mutations; loss of weight; hypoalbuminemia; and primary site treated by surgery or radiotherapy. GPA score of nil was assigned to smoking, without sensitive mutations, loss of weight, hypoalbuminemia, and without local treatment of primary site; the corresponding superior alternatives were scored 1.5, 2.0, 1.5, 1.5, and 1.5, respectively. The median survival times of patients with GPA scores of nil to 3.0, 3.5 to 6.0, and 6.5 to 8.0 were 14.2, 29.5, and 56.6 months in the training set (P < 0.001) and 15.2, 31.2, and 54.0 months in the validation set (P < 0.001)., Conclusion: The survival time of patients with NSCLC with bone-only metastasis was dramatically influenced by the presence of the determined prognostic factors. The GPA model developed in this study may be a useful clinical tool to estimate the life expectancy of these patients, and guide treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Lung cancer is the leading cause of cancer mortality worldwide and most patients are unsuitable for 'gold standard' treatment, which is concurrent chemoradiotherapy. CONCORDE is a platform study seeking to establish the toxicity profiles of multiple novel radiosensitisers targeting DNA repair proteins in patients treated with sequential chemoradiotherapy. Time-to-event continual reassessment will facilitate efficient dose-finding., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)