Adjuvant treatment with trastuzumab of patients with HER2-positive, T1a-bN0M0 breast tumors: A systematic review and meta-analysis.

The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently investigated. The aim of this systematic review and meta-analysis was to examine if adjuvant trastuzumab improves the prognosis in these patients. Databases were searched to identify interventional and observational studies evaluating the effect of trastuzumab on breast cancer specific survival (BCSS), disease free survival (DFS), distant recurrence free survival (DRFS), overall survival (OS) or recurrence free survival (RFS). Twelve studies examining the effect of trastuzumab and nine control studies without trastuzumab were identified (n = 6927). Median follow-up was 36-123 months. Significantly improved DFS (Hazard Ratio (HR) 0.14, p < 0.0001) and OS (HR 0.17, p = 0.011) were found for patients receiving trastuzumab and chemotherapy compared to no trastuzumab/chemotherapy based on four and two studies. The prognosis was good even for patients without trastuzumab treatment: 5-year DFS 88.3% and 5-year OS 95.9%.

The prevalence of sarcopenia and cachexia in older patients with localized colorectal cancer.

INTRODUCTION: The incidence of colorectal cancer (CRC) increases with age. In combination with an ageing population, the number of older patients undergoing surgical treatment for CRC is therefore expected to increase. Sarcopenia and cachexia are potentially modifiable risk factors of a negative surgical outcome. Sarcopenia can be categorized into primary (age-related) and secondary where diseases, such as malignancy, are influential factors. We aimed to investigate the prevalence of preoperative sarcopenia and cachexia in older (≥65 years) vulnerable patients with localized CRC. MATERIALS AND METHODS: Patients included in the randomized study "Geriatric assessment and intervention in older vulnerable patients undergoing resection for colorectal cancer," were screened for sarcopenia and cachexia prior to surgery. All patients in the present cohort were considered vulnerable with Geriatric 8 ≤ 14 points. Sarcopenia was defined according to European Guidelines (EWGSOP2), based on low muscle strength-low handgrip-strength and/or slow 5xChair-Stand-Test-and low appendicular lean mass assessed by dual-energy X-ray absorptiometry. Cachexia was defined as self-reported unintended weight loss >5% within three months or 2-5% with body mass index <20 kg/m2. RESULTS: Sixty-four patients (mean age 79.6 years ±6.4 years, 36 women) were assessed. Of these, 28% (n = 18, 11 women) had low muscle strength and 13% (n = 8, 4 women) fulfilled the criteria for sarcopenia, however, 33% (n = 21, 13 women) had low muscle mass. There was no correlation between low muscle strength and low muscle mass (r = 0.16, P = 0.22). The prevalence of cachexia was 36% (n = 23, 16 women). Low muscle mass was associated with cachexia (φ = 0.38, P = 0.005), but there was no association between sarcopenia and cachexia (φ = 0.01, P = 1.0). DISCUSSION: Despite the included patients who fulfilled the criteria for vulnerability according to G8, relatively few (28%) had low muscle strength. Moreover, there was poor overlap between the prevalence of sarcopenia according to the EWGSOP2 guidelines (13%) and prevalence of low muscle mass (33%) in older patients with CRC. Of note also, there was no association between sarcopenia and cachexia, but an association between cachexia and low muscle mass, which highlights the importance of assessing muscle mass in patients with cancer. TRIAL REGISTRATION: The GEPOC trial has been prospectively registered at http://clinicaltrials.gov (NCT03719573).

COLAR: open-label clinical study of IL-6 blockade with tocilizumab for the treatment of immune checkpoint inhibitor-induced colitis and arthritis.

BACKGROUND: Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies of alternatives to glucocorticoids are lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis and arthritis. PATIENTS AND METHODS: Patients with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade >1 ICI-induced colitis/diarrhea (n=9), arthritis (n=9), or both (n=2) were recruited and treated with tocilizumab (8 mg/kg) every 4 weeks until worsening or unacceptable toxicity. Patients were not allowed to receive systemic glucocorticoids and other immunosuppressive drugs within the 14-day screening period. The primary endpoint was clinical improvement of colitis and arthritis, defined as ≥1 grade CTCAE reduction within 8 weeks. Secondary endpoints were improvements and glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, and histological changes; and changes in plasma concentrations of C reactive protein, cytokines (IL-6, IL-8, and IL-17), and YKL-40. RESULTS: Nineteen patients were available for efficacy analysis; one patient was excluded due to pancreatic insufficiency-induced diarrhea. Patients received treatment with pembrolizumab (n=10) or nivolumab (n=4) as monotherapy or ipilimumab and nivolumab (n=5) combined. Seven patients had been initially treated with glucocorticoids, and two of them also received infliximab. Ten patients continued ICI therapy during tocilizumab treatment. The primary endpoint was achieved in 15 of 19 (79%) patients. Additional one patient had ≥1 grade reduction at week 10, and another patient had stabilized symptoms. At week 24, ongoing improvement without glucocorticoids (n=12), including complete remission (n=10), was noted. Five patients had grades 3-4 treatment-related adverse events, which were manageable and reversible. CONCLUSIONS: Tocilizumab showed promising clinical efficacy and a manageable safety profile in the treatment of ICI-induced colitis and arthritis. Our findings support the feasibility of randomized trials of immune-related adverse events. TRIAL REGISTRATION NUMBER: NCT03601611.

Immune checkpoint Inhibitor-Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management. METHODS: Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis. RESULTS: The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis. CONCLUSION: Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.

Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer.

YKL-40 (also named chitinase 3 like-1 protein [CHI3L1]) is a secreted chitinase-like protein which is upregulated in cancers and suggested to have pro-tumorigenic activity. YKL-40 lacks enzymatic function, but it can bind carbohydrates such as chitin. Chitooligosaccharides (COS) derived from deacetylation and hydrolysis of chitin might be used for the blockade of YKL-40 function. Here, public single-cell RNA sequencing datasets were used to elucidate the cellular source of YKL-40 gene expression in human tumors. Fibroblasts and myeloid cells were the primary sources of YKL-40. Screening of YKL-40 gene expression in syngeneic mouse cancer models showed the highest expression in the Lewis lung carcinoma (LL2) model. LL2 was used to investigate COS monotherapy and combinations with immune checkpoint inhibitors (anti-PD-L1 and anti-CTLA-4) (ICIs) and radiotherapy (8 Gy × 3) (RT). COS tended to reduce plasma YKL-40 levels, but it did not affect tumor growth. LL2 showed minimal responses to ICIs, or to RT alone. Interestingly, ICIs combined with COS led to delayed tumor growth. RT also enhanced the efficacy of ICIs; however, the addition of COS did not further delay the tumor growth. COS may exert their anti-tumorigenic effects through the inhibition of YKL-40, but additional functions of COS should be investigated.

High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI AIM)-a randomized controlled trial.

BACKGROUND: The increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer. METHODS: HI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO2 max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes. DISCUSSION: To our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on February 10th 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT04263467.

A Randomized Placebo-Controlled Phase 2 Study of Gemcitabine and Capecitabine with or without T-ChOS as Adjuvant Therapy in Patients with Resected Pancreatic Cancer (CHIPAC).

The antitumor activity of chitooligosaccharides has been suggested. This phase 2 trial evaluated the efficacy and safety of T-ChOS™, in addition to adjuvant chemotherapy, in patients after resection of pancreatic ductal adenocarcinoma (PDAC). In this single-center, randomized, double-blind, placebo-controlled trial using patients ≥18 years of age after complete macroscopic resection for PDAC, patients were randomly assigned (1:1) to either a continuous oral T-ChOS group or a placebo group, in combination with gemcitabine (GEM) and oral capecitabine (CAP), for a maximum of six cycles. The primary endpoint was disease-free survival (DFS). Recruitment was stopped prematurely in July 2018, with 21 of planned 180 patients included, due to poor accrual and because modified FOLFIRINOX replaced GEM/CAP for the target population. Nine patients received T-ChOS and twelve received the placebo. The median DFS was 10.8 months (95% CI 5.9-15.7) for the T-ChOS arm and 8.4 months (95% CI 0-21.5) in the placebo arm. Overall, seven patients (78%) in the T-ChOS arm and eight patients (67%) in the placebo arm experienced at least one grade 3-4 treatment-related adverse event, most frequently neutropenia. Altogether, the addition of T-ChOS to chemotherapy in patients after resection of PDAC seems safe. However, the clinical benefit cannot be assessed due to the premature cessation of the trial.

Patients' Experience of Communication During Their Course of Treatment in an Oncology Outpatient Clinic: Qualitative Study.

BACKGROUND: Communication between patients and healthcare professionals becomes increasingly important as patients with cancer are primarily treated in outpatient settings, where the time to communicate is brief. There is a need to understand patients' experiences of communication to ensure person-centered communication during treatment. OBJECTIVE: The aim of this study was to explore how patients experience communication with healthcare professionals during their course of treatment in an oncology outpatient clinic to elucidate how their needs for support are met. METHODS: Data were generated through semistructured qualitative interviews in patients with cancer who received treatment in an oncology outpatient clinic (n = 18). Interpretive description methodology and symbolic interactionism inspired the analytical approach. RESULTS: Three overarching communication categories were generated, namely, verbal practices, relational practices, and nonverbal practices, which reflect distinct characteristics and the quality of the communication. Communication was characterized as being informative, cheerful, and routinized, which the patients found supportive and, contrarily, superficial, task focused, lacking continuity in care, and missing existential dimensions. CONCLUSION: The communication practice in the oncology outpatient clinic especially supported patients in managing their treatment and side effects. However, psychological, social, and existential concerns were rarely addressed, requiring the patient to self-manage these issues in everyday life while living with cancer. IMPLICATIONS FOR PRACTICE: Patients are socialized by verbal and nonverbal communication practices in the outpatient clinic, which influences their expectations of what to talk about during their treatment. Methods are needed to support person-centered communication in outpatient settings, so patient care needs are met more broadly.

"Doing What Only I Can Do": Experiences From Participating in a Multimodal Exercise-Based Intervention in Older Patients With Advanced Cancer-A Qualitative Explorative Study.

BACKGROUND: Sparse evidence exists regarding the feasibility and patients' experiences of exercise programs among older cancer populations. OBJECTIVE: The aim of this study was to explore the experiences of older patients with advanced cancer who participated in a 12-week supervised and multimodal exercise program in a hospital setting. METHODS: Individual interviews were conducted with 18 participants (≥65 years) with advanced cancer who completed the intervention program regardless of compliance rate. In addition, written evaluation questionnaires were collected. Data were analyzed using thematic analysis. RESULTS: Three main themes were identified: (1) Motivated to strengthen body and mind, with the subthemes "Doing what only I can do" and "Reaching goals with support from healthcare professionals and peers"; (2) Exercise as an integrated part of the treatment course; and (3) Overcoming undeniable physical limitations. CONCLUSIONS: The participants experienced several benefits from participation, including physical improvements, increased energy, reduction of symptoms, and improved social engagement. Goal setting, being positively pushed and cheered on, and integration of fun games increased motivation. In contrast, being pushed beyond physical limitations and experiencing severe symptoms were experienced as barriers toward exercising. Adherence to the exercise program was facilitated by coordinating a tailored program with medical appointments and receiving comprehensive support and guidance. IMPLICATIONS FOR PRACTICE: Multimodal exercise programs seem to be beneficial for older patients with advanced cancer and should be coordinated with oncological treatment in combination with targeted support and advice on symptom management.

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.

Introduction: Several immune checkpoint inhibitors (CPIs) are under clinical development in hepatocellular carcinoma (HCC) and the field is advancing rapidly. In this comprehensive review, we discuss published results and report on ongoing clinical trials. Methods: A literature search was carried out using PubMed and EMBASE; data reported at international meetings and clinicaltrials.gov were included as well. The search was updated 5 March 2021. We evaluated studies with monotherapy CPI's, combinations of CPI's and combinations of CPI's with other treatment modalities separately. Only studies with at least 10 included patients were considered. Results: We identified 2649 records published in the English language literature. After review, 29 studies remained, including 12 studies with preliminary data only. The obtained overall response rate of PD-1/PDL-1 monotherapy in phase II studies in the second-line setting was 15-20% with disease control in approximately 60% of patients. The responses were of long duration in a subset of patients. Furthermore, the safety profiles were manageable. However, a phase III study comparing nivolumab with sorafenib in the first-line setting and a phase III study evaluating pembrolizumab versus best supportive care in the second-line setting did not meet their prespecified endpoints. More recently, a phase I/II study of nivolumab and ipilimumab has resulted in a response rate of approximately 30% with a median OS of 22 months in the second-line setting. Multiple trials have been initiated to evaluate CPIs in combination with molecularly targeted drugs, especially anti-angiogenic drugs or local therapy. A phase III study investigating atezolizumab plus bevacizumab versus sorafenib in the first-line setting showed significantly increased survival in the combination arm. Conclusions: The combination of atezolizumab and bevacizumab represents a new standard of care in the first-line setting for fit patients with preserved liver function. CPIs can produce durable tumor remission and induce long-standing anti-tumor immunity in a subgroup of patients with advanced HCC. Although phase III trials of CPI monotherapy have been negative, the combination of PD-1/PD-L1 inhibitors with other anti-angiogenic drugs, CTLA-4 inhibitors or other modalities may result in new treatment options for patients with HCC. Research on predictive biomarkers is crucial for further development of CPIs in HCC.

Exercise in older women with breast cancer during systemic therapy: study protocol of a randomised controlled trial (BREACE).

INTRODUCTION: Exercise interventions have been widely investigated in patients with cancer and demonstrate beneficial effects. However, intervention studies that include older women with breast cancer exercising during medical treatment are scarce. Hence, the aim of this study is to investigate the effect of a 12-week exercise-based intervention in older women (≥65 years) with breast cancer receiving (neo)adjuvant or first-line or second-line systemic therapy. METHODS AND ANALYSIS: This is a single-centre, two-armed randomised controlled trial. We anticipate including 100 patients, who will be randomised 1:1 to exercise-based intervention or control stratified by treatment setting ((neo)adjuvant or metastatic) and treatment (chemotherapy or endocrine therapy + cyclin-dependent kinase (CDK) 4/6 inhibitors). The intervention group will receive standard oncological treatment and a 12-week supervised exercise-based intervention comprising a progressive resistance exercise programme two times per week, a protein supplement after exercise and a home-based walking programme based on daily step counts. The control group will receive standard oncological treatment. Assessments will be performed at baseline and 6, 12 and 24 weeks after start of the intervention. Primary outcome is physical function, measured by the 30-second Chair Stand Test. Secondary outcomes are feasibility (compliance and adherence to intervention), objective and patient-reported functional measures (6-meter and 10-meter gait speed; 6-min Walk Test; Handgrip Strength; Stair Climb Test; Physical Activity Questionnaire), symptom burden and well-being (MD Anderson Symptom Inventory; Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and B23), body composition (dual-energy X-ray absorptiometry scan), side effects, inflammatory biomarkers, hospitalisation and survival. ETHICS AND DISSEMINATION: The protocol was reviewed and accepted by the Scientific Ethics Review Committee of the Capital Region of Denmark, 17 June 2018 (VEK ref.: H-18021013). Trial results will be submitted for publication in a peer-reviewed journal and presented on conferences, in oncology wards, exercise centres in municipalities and patient organisations, ensuring dissemination to relevant stakeholders. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ on 3 September 2018. Identifier: NCT03656731.

The effect of exercise-based interventions on health-related quality of life and physical function in older patients with cancer receiving medical antineoplastic treatments: a systematic review.

Older patients with cancer are underrepresented in trials investigating the effect of exercise therapy. The aim of this systematic review was to investigate the effect of exercise therapy during medical antineoplastic treatment in older patients (≥ 65 years) with cancer. A systematic review following the Cochrane guidelines was performed. Randomized controlled trials were identified through a systematic literature search in MEDLINE, EMBASE, CENTRAL, and CINAHL up to December 2019. Study selection was performed independently by two reviewers. Four randomized controlled trials published between 2014 and 2019 were included comprising a total of 412 participants. Most participants were diagnosed with breast, prostate or colorectal cancer. The studies were characterized by large differences in design, interventions and outcomes, which prevented meta-analyses. The interventions ranged from 4 weeks to 12 months and involved both supervised and unsupervised exercise programs. Some evidence of beneficial effects from the interventions were documented on physical function, muscle strength, physical activity and cognitive function. No evidence of effects was found for health-related quality of life, aerobic capacity, body composition, cancer-related symptoms and side effects, or for any clinical outcomes. No adverse events were reported. Exercise therapy seems to be safe and feasible in older patients with cancer. However, due to a limited number of studies, small sample sizes and heterogeneity across study design, the effects of exercise in older patients with cancer receiving medical antineoplastic treatment are inconclusive.

ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer.

In this study we investigated the use of cancer cell protein expression of ABCG2 to predict efficacy of systemic first-line irinotecan containing therapy in patients with metastatic colorectal cancer (mCRC). From a Danish national cohort, we identified 119 mCRC patients treated with irinotecan containing therapy in first-line setting. Among these, 108 were eligible for analyses. Immunohistochemistry (IHC) analyses were performed on the primary tumor tissue in order to classify samples as high or low presence of ABCG2 protein. Data were then associated with patient outcome (objective response (OR), progression free survival (PFS) and overall survival (OS)). ABCG2 protein expression in the basolateral membrane was high (score 3+) in 33% of the patients. Exploratory analyses revealed a significant interaction between ABCG2 score, adjuvant treatment and OR (p = 0.041) in the 101 patients with evaluable disease. Patients with low ABCG2 (score 0-2) and no prior adjuvant therapy had a significantly higher odds ratio of 5.6 (Confidence Interval (CI) 1.68-18.7; p = 0.005) for obtaining OR. In contrast, no significant associations between ABCG2 expression and PFS or OS were found. These results suggest that measurement of the ABCG2 drug efflux pump might be used to select patients with mCRC for irinotecan treatment. However, additional studies are warranted before conclusions regarding a clinical use can be made. Moreover, patients with high ABCG2 immunoreactivity could be candidates for specific ABCG2 inhibition treatment in combination with irinotecan.

Incidence and risk markers of 5-fluorouracil and capecitabine cardiotoxicity in patients with colorectal cancer.

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity.Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007-2016), adjuvant (2000-2016) or metastatic setting (2007-2016).Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8-6.6%] and 4.1% (95% CI: 3.0-5.2%) induced by capecitabine (p = .21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p = .53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p = .53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p = .34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p = .76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p = .50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p = 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2-7.0, p = .016).Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine.

Attitudes towards physical activity and exercise in older patients with advanced cancer during oncological treatment - A qualitative interview study.

PURPOSE: Older patients with cancer are underrepresented in exercise-based trials. To engage older patients in physical activity (PA), it is necessary to consider age-related decline in health, comorbidities and practicalities. The study aim was to explore attitudes towards PA and exercise among older patients with cancer to inform future exercise-based interventions. METHOD: Individual interviews (N = 23) were conducted in patients ≥ 65 years with advanced lung, biliary tract and pancreatic cancer receiving palliative oncological treatment. Patients were recruited with a purposive sampling strategy. A semi-structured interview guide focusing on attitudes towards PA and exercise, including barriers, facilitators and motivators, was used. Data on the informants' medical history, demographics and PA level was collected. RESULTS: Identified themes were: 1) a general positive perception of physical activity is expressed 2) comorbidities and external circumstances prevent physical activity, 3) fatigue overshadows life, 4) social support is key to short and long-term motivation, 5) fixed conditions keep one focused, 6) familiarity raises confidence and motivation. CONCLUSIONS: Even though perceptions of PA were positive among older patients with cancer, most struggled to stay physically active during oncological treatment. Several factors related to cancer and aging were identified as barriers; most profoundly was the overwhelming feeling of fatigue. Improving physical and mental well-being, fixed conditions (e.g. group-based exercise and supervision) and social support were identified as motivators and facilitators. Preferences for PA varied, but activities that were familiar increased motivation. Exercise programs for older patients with cancer must be adjustable to each patient's limitations, needs and personal resources.

Two open-label, single arm, non-randomized phase II studies of irinotecan for the treatment of metastatic breast cancer in patients with increased copy number of the topoisomerase I gene.

BACKGROUND: Treatment options in metastatic breast cancer are limited. New therapies preferable with predictive biomarkers are needed. The aim of these trials was to investigate if gene copy number of the topoisomerase 1 gene was predictive of response to the topoisomerase inhibitor irinotecan. METHODS: Two open-label, single-arm phase II studies including HER2 positive and negative patients were conducted. Patients were eligible for inclusion if the primary tumor or a metastatic lesion had increased expression of the topoisomerase 1 gene defined as a TOP1 gene copy number of ≥4 or a TOP1/CEN20 ratio of ≥2. Patients were treated with irinotecan +/- trastuzumab weekly for 4 weeks following 2 weeks break, until progression or unacceptable toxicities. Evaluation scans were performed every 6 weeks. Primary endpoint was clinical benefit rate defined as the fraction of patients with stable disease for ≥4 months. RESULTS: The pre-planned number of 18 patients in each trial was not reached, thus no formal statistical analysis could be performed. Nine patients with HER2 negative disease and three patients with HER2 positive disease were included. Three patients obtained a partial remission and two patients had SD. CONCLUSIONS: The trials did not include the planned number of patients. No association between gene copy number of the topoisomerase 1 gene and response to irinotecan could be proved, however a clinical benefit was found in 5/12 patients and in 2/3 patients with HER2 positive disease. This could call for further investigation of the drug in the metastatic setting, especially in HER2 positive BC. TRIAL REGISTRATION: Eudract registration numbers 2012-002348-26 and 2012-002347-23 . Registration date August 20th 2012.

Observations of the communication practices between nurses and patients in an oncology outpatient clinic.

PURPOSE: Effective communication in cancer care and treatment is linked to better health outcomes, improved treatment adherence, and improved quality of life for cancer patients. While the characteristics of effective communication have been identified, there is sparse knowledge about the current conditions for providing effective communication especially within the outpatient clinical context, where the majority of cancer patients are currently being treated. This study aimed to explore communication practices between nurses and patients undergoing chemotherapy in an outpatient clinic to gain insight into how patients are supported in this setting. METHODS: Data were collected through 70 h of participant observations of nurse-patient interactions supplemented with ad hoc interviews with nurses in an oncology outpatient clinic. The methodology and data analysis are guided by interpretive description, thematic analysis and symbolic interactionism. RESULTS: Three themes were generated that characterised communication in the outpatient clinic: Treatment-centred communication, efficient communication and spatially-bound communication. While there was good opportunity for patients to learn about treatment and side effects during cancer treatment, psychosocial concerns were rarely addressed. CONCLUSIONS: The outpatient setting influences the type and quality of communication between nurses and patients. Improvement of communication should include not only verbal and written information, but focus on the importance of nonverbal communication in the oncology outpatient clinic. Furthermore, there is a need to make environmental adjustments that can facilitate the opportunity for patients to express their needs and for nurses to respond to them.

Systematic review: Incidence, risk factors, survival and treatment of bone metastases from colorectal cancer.

BACKGROUND: Bones are not considered a frequent metastatic site in patients with colorectal cancer (CRC). The purpose of the present study was to determine the incidence of bone metastases (BM) in CRC, to identify possible risk factors for BM, survival after BM, and effect of treatment of BM including antiresorptive treatment. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed and EMBASE. RESULTS: We included 29 studies. One randomized placebo controlled trial (RCT) study, two autopsy studies, five register studies, and twenty retrospective cohort studies. The studies described different cohorts making direct comparison difficult. Three studies analysed the effect of different treatments for BM including one RCT study. CONCLUSION: The incidence of bone metastases was 3-7% in patients with CRC, and it was not possible to detect an increase in incidence over time. The most well established risk factors for BM are rectal cancer, having lymph node invasion at surgery of primary tumor, and lung metastases at any time. Other risk factors such as RAS mutation status have been suggested but results are not conclusive. Survival ranges from 5 to 21 months after diagnosis of BM depending on cohort, with survival of about 8 months in unselected patients. Several variables have been suggested as potential prognostic markers but are all poorly investigated. Treatment of BM is not well investigated, though patients seem to benefit from bisphosphonate treatment with regard to lower risk of skeletal related events. This review highlights the need for new research in the area.

Engaging the older cancer patient; Patient Activation through Counseling, Exercise and Mobilization - Pancreatic, Biliary tract and Lung cancer (PACE-Mobil-PBL) - study protocol of a randomized controlled trial.

BACKGROUND: Several intervention studies have demonstrated that exercise training has beneficial effects among cancer patients. However, older cancer patients are underrepresented in clinical trials, and only few exercise-based studies have focused specifically on older patients with cancer. In particular, research investigating the effects of exercise training among older patients with advanced cancer is lacking. The purpose of the current study is to investigate the effect of a 12-week multimodal and exercise-based intervention among older patients (≥65 years) with advanced pancreatic, biliary tract or lung cancer, who are treated with first-line palliative chemotherapy, immunotherapy or targeted therapy. METHODS: PACE-Mobil-PBL is a two-armed randomized controlled trial. Participants will be randomized 1:1 to an intervention group (N = 50) or a control group (N = 50). Participants in the intervention group will receive standard oncological treatment and a 12-week multimodal intervention, comprised of: (I) supervised exercise training, twice weekly in the hospital setting, (II) home-based walking with step counts and goal-setting, (III) supportive and motivational nurse-led counseling, and (IV) protein supplement after each supervised training session. Participants in the control group will receive standard oncological treatment. The primary outcome is physical function measured by the 30-s chair stand test. Secondary outcomes include measures of feasibility, activity level, physical capacity and strength, symptom burden, quality of life, toxicity to treatment, dose reductions, inflammatory biomarkers, body weight and composition, hospitalizations and survival. Assessments will be conducted at baseline, and after 6, 12 and 16 weeks. DISCUSSION: The current study is one of the first to investigate the effect of an exercise-based intervention specifically targeting older patients with advanced cancer. PACE-Mobil-PBL supports the development of health promoting guidelines for older patients with cancer, and the study results will provide new and valuable knowledge in this understudied field. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on January 26, 2018 (ID: NCT03411200 ).

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer.

BACKGROUND: Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. METHODS: In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). RESULTS: In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). CONCLUSION: In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.