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  • Journal of Clinical Oncology

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Kelly D. Getz; Lillian Sung; Bonnie Ky; Robert B. Gerbing; +7 Authors

    Purpose Late cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS). Methods Cardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children’s Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions. Results Approximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387). Conclusion Early treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Other literature type . 2018
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Journal of Clinical Oncology
    Article . 2019
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Other literature type . 2018
      Data sources: PubMed Central
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      Journal of Clinical Oncology
      Article . 2019
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  • Authors: Kristin L. Campbell; Sarah Weller; Prue Cormie; Kirstin Lane; +2 Authors

    e24042 Background: Exercise has been shown to improve physical function and quality of life in individuals with bone metastases. To facilitate better integration of exercise services into clinical care for these more complex patients, the purpose was to understand the current views of an expert panel on the appropriate exercise screening approach for adults with bone metastases. Methods: Physicians, physical therapists and exercise physiologists with clinical or research expertise in providing medical and/or exercise advice to individuals with bone metastases were identified. A 3-round modified online Delphi survey was used to establish a consensus, with a priori consensus set to 70%. Results: Response rates were 68% (73/107), 81% (59/73) and 97% (57/59) for each Delphi round. Key consensus points were: a) medical guidance (i.e. communication and medical information from a physician) is recommended prior to commencing structured exercise for all individuals with bone lesions (90% consensus) and is required when individuals present with bone pain, have received past medical treatment for bone pain, or have a history of disease-related fractures (90% consensus); b) the primary objective of exercise professionals for seeking medical guidance is to obtain medical information (e.g., bone scan reports) to guide clinical decision making for exercise prescription (93% consensus) and for bi-directional communication (i.e., for overall patient care and safety) (75% consensus) versus requiring a direct referral from a physician for liability coverage (39% consensus); c) the physician group that exercise professionals most commonly approach for medical guidance are medical oncologists (84% consensus) or radiation oncologists (63% consensus) compared to primary care providers (33% consensus), orthopedic surgeons (40% consensus) or physiatrists (16%); d) as part of pre-exercise screening by an exercise professional, information should be collected on the number, location and type of bone lesion(s), level of bone pain and any other bone-related symptom (100% consensus). Conclusions: This represents the current views of a range of physicians, physical therapists, exercise physiologists and researchers who provide medical and/or exercise advice to adults with bone metastases. These findings will inform the work of the International Bone Metastases Exercise Working Group to establish the first exercise guidelines for adults with bone metatases.

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  • Authors: Anthony Fyles; Melania Pintilie; David W. Hedley; Robert E. Bristow; +3 Authors

    5584 Background: Chemoradiotherapy (CRT) has been shown to improve survival compared to RT alone for locally advanced cervix cancer. The tumour microenvironment in cervix cancer is also known to influence disease progression and response to treatment. In this prospective study, pre-treatment tumour hypoxia and interstitial fluid pressure (IFP) were examined as potential biomarkers of improved treatment effectiveness in a cohort of patients treated with definitive radiation alone, or with the addition of concurrent cisplatin CRT. Methods: Between April 1994 and January 2006, 309 eligible patients with cervix cancer were entered into a prospective study of hypoxia and IFP prior to definitive treatment. Patients accrued between 1994 and 1999 (n = 115) were treated with RT alone, and those accrued between 2000 and 2006 (n = 194) received RT and concurrent weekly cisplatin CRT. Clinical characteristics were similar between the two cohorts except pelvic lymph node metastases were more frequent in the CRT cohort (42% vs. 19%, p = 0.0005), likely due to changes in definition of positive nodes on CT or MR imaging. The median follow-up was 3.6 years (2.9 years for CRT and 7.8 years for RT). Results: The use of CRT improved outcome in hypoxic tumors compared to RT (57% 3-yr DFS vs. 42%, p = 0.045) with a trend to improved DFS in patients with high IFP tumors (57% 3-yr DFS vs. 44% for RT alone, p = 0.056). A strong interaction was identified between IFP and treatment (CRT vs. RT, p = 0.007). After correcting for the effects of clinical prognostic factors, cisplatin significantly improved DFS in the high IFP group (p = 0.02), and showed a trend towards improved DFS in those with hypoxia (p = 0.1). In patients with both high IFP and hypoxia a similar benefit of cisplatin was seen. Conclusions: Patients with high IFP and hypoxic tumours may selectively benefit from the addition of concurrent cisplatin CRT to their treatment regimen. This observation is contrary to an effect of high IFP on impaired drug delivery, but may reflect reduced DNA repair under hypoxic conditions, which could facilitate cell killing with both radiation and cisplatin chemotherapy. No significant financial relationships to disclose.

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  • Authors: Paul Nathan; Sumit Gupta; David Hodgson;
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  • Authors: Jorge E. Cortes; Jane F. Apperley; Elza Lomaia; Beatriz Moiraghi; +16 Authors

    7000 Background: PON, a third-generation tyrosine kinase inhibitor (TKI), demonstrated deep and long-lasting responses and survival in patients (pts) with chronic-phase chronic myeloid leukemia (CP-CML) resistant/intolerant to second-generation TKI therapy (PACE; NCT01207440); post hoc analysis suggested a relationship between dose and both adverse events and response. Here we present the primary analysis of OPTIC (NCT02467270), an ongoing, randomized, phase 2 trial with a novel response-based dosing regimen of PON in pts with resistant/intolerant CP-CML. Methods: Pts with CP-CML resistant/intolerant to ≥2 TKIs or with the BCR-ABL1 T315I mutation were randomized to PON starting doses of 45 mg (cohort A; 45 mg → 15 mg), 30 mg (B; 30 mg →15 mg), and 15 mg (C) once daily. Doses were reduced to 15 mg with achievement of ≤1% BCR-ABL1IS in cohorts A and B. The primary endpoint is ≤1% BCR-ABL1IS at 12 mo; secondary endpoints include cytogenetic and molecular responses and safety outcomes. AOEs were adjudicated prospectively by an independent review committee. Results: 283 pts were randomized (A/B/C: n=94/95/94) and had the following baseline characteristics: median age 48 y (18‒81 y); 98% received ≥2 (55% ≥3) TKIs; 99% had resistant disease; 40% had ≥1 baseline mutations (23% T315I). At the primary analysis with 32 mo median follow-up, 134 pts (47%; n=50/41/43) remained on treatment and 204 pts (72%) had PON exposure ≥12 mo. At 12 mo, 44% (41/93) in A, 29% (27/93) in B, and 23% (21/91) in C achieved ≤1% BCR-ABL1IS (Table); primary endpoint was met by cohort A. Dose reductions to 15 mg after achieving response (A/B) were 48/29%. Most common grades ≥3 TEAEs were thrombocytopenia, 27%; neutropenia, 17%; and anemia, 7%. AOEs/serious AOEs were reported in cohorts A (10%/4%), B (5%/4%), and C (3%/3%). Dose reductions or discontinuations for TEAEs (A/B/C) were 46/35/32% and 19/16/14%, respectively. Conclusions: The OPTIC primary analysis demonstrates the optimal benefit:risk profile for PON was achieved with a response-based dosing regimen starting with 45 mg/d, followed by dose reduction to 15 mg/d upon achieving ≤ 1% BCR-ABL1IS; 30 mg→15 mg and 15 mg cohorts may provide benefit, especially in pts without T315I mutation (Table). The observed ≤1% BCR-ABL1IS responses are supported by robust survival outcomes in pts with CP-CML resistant to second-generation BCR-ABL1 TKI therapy, both with and without BCR-ABL1 mutations. Clinical trial information: NCT02467270. [Table: see text]

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  • Authors: Aleksandra Paliga; Horia Marginean; Bibianna Purgina; Basile Tessier; +2 Authors

    3109 Background: This study investigates the prognostic value of overexpression of EGFR, HER2 and c-Met by immunohistochemistry (IHC) in Canadian patients with GC and correlates expression with cli...

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  • Authors: Matthew Castelo; Rinku Sutradhar; Neil Faught; Danilo Giffoni M. M. Mata; +6 Authors

    577 Background: The Choosing Wisely guidelines recommend against surgical axillary staging (AS) in women ≥70 years with ER+/HER2- early stage breast cancer (BC). However, there has been little change in practice patterns, which may be influenced by observational studies reporting worse survival among women not receiving AS. Previous analyses did not take into account comorbidities, specific adjuvant treatments and HER2 status which may confound the association between AS omission and survival. This study examined the impact of AS omission on survival in older patients with Stage I/II BC, and secondarily emulated the Choosing Wisely population in a subgroup of those ≥70 years undergoing sentinel node biopsy (SLNB) vs. no AS for ER+/HER2- tumors. Methods: This was a population-based cohort study using linked health administrative data in Ontario, Canada. From the Ontario Cancer Registry, we identified women aged 65-95 years who underwent surgery for Stage I/II BC between 2010 and 2016. We excluded women who received neoadjuvant chemotherapy. To address confounding between those who did and did not receive AS, we built a propensity score model including patient and disease characteristics. Patients were weighted by propensity scores using overlap weights. Association with overall survival (OS) was calculated using weighted Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using weighted Fine and Gray models, adjusting for biomarkers and adjuvant treatments. Adjuvant treatment receipt was modelled with weighted log-binomial models. Results: Among 17,546 older women, 1,807 (10.3%) did not undergo AS, who were older, more comorbid, less likely to undergo mastectomy, and more likely to have tumors ≥ 2 cm. After propensity score weighting, baseline characteristics including comorbidity were balanced between the two groups. Women who did not undergo AS were less likely to receive adjuvant chemotherapy (adjusted RR 0.70. 95% CI 0.58-0.84), endocrine therapy (adjusted RR 0.85, 95% CI 0.82-0.89) and radiotherapy (adjusted RR 0.69, 95% CI 0.65-0.73). Unadjusted 5-year survival was lower for women who did not undergo AS (68.1%, 95% CI 65.8-70.2 vs. 87.6%, 95% CI 87.0-88.1; p< 0.001), and there was a higher 5-year incidence of BC deaths (7.6%, 95% CI 6.2-9.2 vs. 4.3%, 95% CI 3.9-4.7; p< 0.001). After weighting and adjustment, women who did not undergo AS continued to have worse OS (adjusted HR 1.13, 95% CI 1.03-1.24), however, there was no significant difference in BCSS (adjusted HR 1.00, 95% CI 0.78-1.26). The results among 6,286 ER+/HER2- women ≥70 years undergoing SLNB vs. no AS were similar for OS (adjusted HR 1.22, 95% CI 1.05-1.42) and BCSS (adjusted HR 1.08, 95% CI 0.67-1.76). Conclusions: The omission of AS in older women with early stage BC was associated with worse OS, reflecting selection bias, but no significant difference in BCSS.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Katherine M.W. Pisters; Eric Vallières; John Crowley; Wilbur A. Franklin; +5 Authors

    Purpose Patients with early-stage non–small-cell lung cancer (NSCLC) have a poor prognosis even after complete resection. Earlier studies of preoperative (induction) chemotherapy in resectable NSCLC demonstrated feasibility and encouraging survival data. This randomized phase III trial compared overall survival (OS) for preoperative paclitaxel and carboplatin followed by surgery with surgery alone in patients with early-stage NSCLC. Patients and Methods Patients with clinical stage IB-IIIA NSCLC (excluding superior sulcus tumors and N2 disease) were eligible. Patients were randomly assigned to surgery alone or to three cycles of paclitaxel (225 mg/m2) and carboplatin (area under curve, 6) followed by surgical resection. The primary end point was OS; secondary end points were progression-free survival (PFS), chemotherapy response, and toxicity. Results The trial closed early with 354 patients after reports of a survival benefit for postoperative chemotherapy in other studies. The median OS was 41 months in the surgery-only arm and 62 months in the preoperative chemotherapy arm (hazard ratio, 0.79; 95% CI, 0.60 to 1.06; P = .11.) The median PFS was 20 months for surgery alone and 33 months for preoperative chemotherapy (hazard ratio, 0.80; 95% CI, 0.61 to 1.04; P = .10.) Major response to chemotherapy was seen in 41% of patients; no unexpected toxicity was observed. Conclusion This trial closed prematurely after compelling evidence supporting postoperative chemotherapy emerged. Although OS and PFS were higher with preoperative chemotherapy, the differences did not reach statistical significance. At present, stronger evidence exists for postoperative chemotherapy in early-stage NSCLC.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Journal of Clinical ...arrow_drop_down
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2010
    Data sources: PubMed Central
    Journal of Clinical Oncology
    Article . 2010
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      Europe PubMed Central
      Other literature type . 2010
      Data sources: PubMed Central
      Journal of Clinical Oncology
      Article . 2010
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    Authors: Siri Rostoft; Anita O'Donovan; Pierre Soubeyran; Shabbir M.H. Alibhai; +1 Authors

    As the majority of patients with cancer are older than 65 years, most medical, surgical, and radiation oncologists treat a large number of older adults in their clinical practice. Older adults are a heterogeneous group of patients, in terms of physiologic reserves, comorbidity, and geriatric conditions such as cognitive impairment and disability. Comorbidities become increasingly common as people age, as does frailty (limited physiologic reserves that increase the risk of negative outcomes).1 Neither chronological age alone nor performance status does justice to characterizing this heterogeneity. Furthermore, since older patients are under-represented in clinical cancer trials, especially if they are frail with comorbidity or functional dependency, traditional treatment algorithms may not be applicable.2,3 As a result, treatment decisions in older adults with cancer are not straightforward.

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    Journal of Clinical Oncology
    Article . 2021
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      Journal of Clinical Oncology
      Article . 2021
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  • Authors: Matthew D. Galsky; Andrea Necchi; Srikala S. Sridhar; Osamu Ogawa; +5 Authors

    TPS504 Background: Despite high response rates with first-Line (1L), standard, platinum-based chemotherapy (CT) (gemcitabine + cisplatin or gemcitabine + carboplatin) for patients (pts) with locally advanced or metastatic urothelial cancer (mUC), prognosis remains poor. Studies of immune checkpoint inhibitors + CT in 1L mUC have demonstrated mixed results. In IMvigor130, an improvement in progression-free survival (PFS) with atezolizumab + CT vs placebo + CT reached statistical significance, although overall survival (OS) had not reached statistical significance at the interim analysis. A subgroup analysis suggested a possible larger effect size for PFS and OS for pts with high PD-L1 expression. In KEYNOTE-361, no improvement in either PFS or OS was observed with pembrolizumab + CT vs CT alone. The combination of durvalumab (anti–PD-L1 antibody) and tremelimumab (anti–CTLA-4 antibody) has shown activity in previously treated mUC. In the DANUBE trial of 1L mUC, the co-primary endpoints were OS compared between durvalumab and CT in pts whose tumor cells and/or tumor-infiltrating immune cells express high levels of PD-L1 (≥25%) and between durvalumab + tremelimumab and CT regardless of PD-L1 expression. While neither co-primary endpoint was met, durvalumab + tremelimumab showed evidence of activity, particularly in the PD-L1–high population (hazard ratio: 0.74 [95% CI 0.59–0.93]). Collectively, these results led to an update to the NILE protocol, focusing on pts with PD-L1–high expression. Methods: NILE (NCT03682068) is a randomized, open-label, multicenter, phase III global trial that will randomize ~1215 previously untreated pts with histologically or cytologically documented, unresectable, locally advanced, or metastatic transitional cell carcinoma of the urothelium. Eligible pts aged ≥18 years will be randomized 1:1:1 to durvalumab + CT (Arm 1), durvalumab + tremelimumab + CT (Arm 2), or CT (Arm 3). A tumor tissue sample for biomarker analysis is mandatory as PD-L1 status is a stratification factor. The original co-primary endpoints were PFS and OS for durvalumab + CT vs CT in the intention-to-treat population. However, based on the DANUBE trial results, the primary endpoint was revised to a co-primary endpoint OS in pts with high PD-L1 expression for Arm 1 vs Arm 3 and Arm 2 vs Arm 3. Secondary endpoints will include OS, OS rate at 24 months, PFS, objective response rate, proportion of pts alive and progression free at 12 months, duration of response, disease control rate, time from randomization to second progression, health-related quality of life, and safety. Pharmacokinetics, immunogenicity, and biomarkers are exploratory endpoints. The study opened for enrollment in September 2018. Clinical trial information: NCT03682068.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Kelly D. Getz; Lillian Sung; Bonnie Ky; Robert B. Gerbing; +7 Authors

    Purpose Late cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS). Methods Cardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children’s Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions. Results Approximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387). Conclusion Early treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Other literature type . 2018
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    Journal of Clinical Oncology
    Article . 2019
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Other literature type . 2018
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      Journal of Clinical Oncology
      Article . 2019
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  • Authors: Kristin L. Campbell; Sarah Weller; Prue Cormie; Kirstin Lane; +2 Authors

    e24042 Background: Exercise has been shown to improve physical function and quality of life in individuals with bone metastases. To facilitate better integration of exercise services into clinical care for these more complex patients, the purpose was to understand the current views of an expert panel on the appropriate exercise screening approach for adults with bone metastases. Methods: Physicians, physical therapists and exercise physiologists with clinical or research expertise in providing medical and/or exercise advice to individuals with bone metastases were identified. A 3-round modified online Delphi survey was used to establish a consensus, with a priori consensus set to 70%. Results: Response rates were 68% (73/107), 81% (59/73) and 97% (57/59) for each Delphi round. Key consensus points were: a) medical guidance (i.e. communication and medical information from a physician) is recommended prior to commencing structured exercise for all individuals with bone lesions (90% consensus) and is required when individuals present with bone pain, have received past medical treatment for bone pain, or have a history of disease-related fractures (90% consensus); b) the primary objective of exercise professionals for seeking medical guidance is to obtain medical information (e.g., bone scan reports) to guide clinical decision making for exercise prescription (93% consensus) and for bi-directional communication (i.e., for overall patient care and safety) (75% consensus) versus requiring a direct referral from a physician for liability coverage (39% consensus); c) the physician group that exercise professionals most commonly approach for medical guidance are medical oncologists (84% consensus) or radiation oncologists (63% consensus) compared to primary care providers (33% consensus), orthopedic surgeons (40% consensus) or physiatrists (16%); d) as part of pre-exercise screening by an exercise professional, information should be collected on the number, location and type of bone lesion(s), level of bone pain and any other bone-related symptom (100% consensus). Conclusions: This represents the current views of a range of physicians, physical therapists, exercise physiologists and researchers who provide medical and/or exercise advice to adults with bone metastases. These findings will inform the work of the International Bone Metastases Exercise Working Group to establish the first exercise guidelines for adults with bone metatases.

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  • Authors: Anthony Fyles; Melania Pintilie; David W. Hedley; Robert E. Bristow; +3 Authors

    5584 Background: Chemoradiotherapy (CRT) has been shown to improve survival compared to RT alone for locally advanced cervix cancer. The tumour microenvironment in cervix cancer is also known to influence disease progression and response to treatment. In this prospective study, pre-treatment tumour hypoxia and interstitial fluid pressure (IFP) were examined as potential biomarkers of improved treatment effectiveness in a cohort of patients treated with definitive radiation alone, or with the addition of concurrent cisplatin CRT. Methods: Between April 1994 and January 2006, 309 eligible patients with cervix cancer were entered into a prospective study of hypoxia and IFP prior to definitive treatment. Patients accrued between 1994 and 1999 (n = 115) were treated with RT alone, and those accrued between 2000 and 2006 (n = 194) received RT and concurrent weekly cisplatin CRT. Clinical characteristics were similar between the two cohorts except pelvic lymph node metastases were more frequent in the CRT cohort (42% vs. 19%, p = 0.0005), likely due to changes in definition of positive nodes on CT or MR imaging. The median follow-up was 3.6 years (2.9 years for CRT and 7.8 years for RT). Results: The use of CRT improved outcome in hypoxic tumors compared to RT (57% 3-yr DFS vs. 42%, p = 0.045) with a trend to improved DFS in patients with high IFP tumors (57% 3-yr DFS vs. 44% for RT alone, p = 0.056). A strong interaction was identified between IFP and treatment (CRT vs. RT, p = 0.007). After correcting for the effects of clinical prognostic factors, cisplatin significantly improved DFS in the high IFP group (p = 0.02), and showed a trend towards improved DFS in those with hypoxia (p = 0.1). In patients with both high IFP and hypoxia a similar benefit of cisplatin was seen. Conclusions: Patients with high IFP and hypoxic tumours may selectively benefit from the addition of concurrent cisplatin CRT to their treatment regimen. This observation is contrary to an effect of high IFP on impaired drug delivery, but may reflect reduced DNA repair under hypoxic conditions, which could facilitate cell killing with both radiation and cisplatin chemotherapy. No significant financial relationships to disclose.

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  • Authors: Paul Nathan; Sumit Gupta; David Hodgson;
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  • Authors: Jorge E. Cortes; Jane F. Apperley; Elza Lomaia; Beatriz Moiraghi; +16 Authors

    7000 Background: PON, a third-generation tyrosine kinase inhibitor (TKI), demonstrated deep and long-lasting responses and survival in patients (pts) with chronic-phase chronic myeloid leukemia (CP-CML) resistant/intolerant to second-generation TKI therapy (PACE; NCT01207440); post hoc analysis suggested a relationship between dose and both adverse events and response. Here we present the primary analysis of OPTIC (NCT02467270), an ongoing, randomized, phase 2 trial with a novel response-based dosing regimen of PON in pts with resistant/intolerant CP-CML. Methods: Pts with CP-CML resistant/intolerant to ≥2 TKIs or with the BCR-ABL1 T315I mutation were randomized to PON starting doses of 45 mg (cohort A; 45 mg → 15 mg), 30 mg (B; 30 mg →15 mg), and 15 mg (C) once daily. Doses were reduced to 15 mg with achievement of ≤1% BCR-ABL1IS in cohorts A and B. The primary endpoint is ≤1% BCR-ABL1IS at 12 mo; secondary endpoints include cytogenetic and molecular responses and safety outcomes. AOEs were adjudicated prospectively by an independent review committee. Results: 283 pts were randomized (A/B/C: n=94/95/94) and had the following baseline characteristics: median age 48 y (18‒81 y); 98% received ≥2 (55% ≥3) TKIs; 99% had resistant disease; 40% had ≥1 baseline mutations (23% T315I). At the primary analysis with 32 mo median follow-up, 134 pts (47%; n=50/41/43) remained on treatment and 204 pts (72%) had PON exposure ≥12 mo. At 12 mo, 44% (41/93) in A, 29% (27/93) in B, and 23% (21/91) in C achieved ≤1% BCR-ABL1IS (Table); primary endpoint was met by cohort A. Dose reductions to 15 mg after achieving response (A/B) were 48/29%. Most common grades ≥3 TEAEs were thrombocytopenia, 27%; neutropenia, 17%; and anemia, 7%. AOEs/serious AOEs were reported in cohorts A (10%/4%), B (5%/4%), and C (3%/3%). Dose reductions or discontinuations for TEAEs (A/B/C) were 46/35/32% and 19/16/14%, respectively. Conclusions: The OPTIC primary analysis demonstrates the optimal benefit:risk profile for PON was achieved with a response-based dosing regimen starting with 45 mg/d, followed by dose reduction to 15 mg/d upon achieving ≤ 1% BCR-ABL1IS; 30 mg→15 mg and 15 mg cohorts may provide benefit, especially in pts without T315I mutation (Table). The observed ≤1% BCR-ABL1IS responses are supported by robust survival outcomes in pts with CP-CML resistant to second-generation BCR-ABL1 TKI therapy, both with and without BCR-ABL1 mutations. Clinical trial information: NCT02467270. [Table: see text]

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