Recent guidelines concerning exercise for people with cancer provide evidence-based direction for exercise assessment and prescription for clinicians and their patients. Although the guidelines promote exercise integration into clinical care for people with cancer, they do not support strategies for bridging the guidelines with related resources or programs. Exercise program accessibility remains a challenge in implementing the guidelines, but that challenge might be mitigated with conceptual frameworks ("pathways") that connect patients with exercise-related resources. In the present paper, we describe a pathway model and related resources that were developed by an expert panel of practitioners and researchers in the field of exercise and rehabilitation in oncology and that support the transition from health care practitioner to exercise programs or services for people with cancer. The model acknowledges the nuanced distinctions between research and exercise programming, as well as physical activity promotion, that, depending on the available programming in the local community or region, might influence practitioner use. Furthermore, the pathway identifies and provides examples of processes for referral, screening, medical clearance, and programming for people after a cancer diagnosis. The pathway supports the implementation of exercise guidelines and should serve as a model of enhanced care delivery to increase the health and well-being of people with cancer.

Objective To evaluate the effectiveness of remote proactive management of toxicities during chemotherapy for early stage breast cancer. Design Pragmatic, cluster randomised trial. Setting 20 cancer centres in Ontario, Canada, allocated by covariate constrained randomisation to remote management of toxicities or routine care. Participants All patients starting adjuvant or neoadjuvant chemotherapy for early stage breast cancer at each centre. 25 patients from each centre completed patient reported outcome questionnaires. Interventions Proactive, standardised, nurse led telephone management of common toxicities at two time points after each chemotherapy cycle. Main outcome measures The primary outcome, cluster level mean number of visits to the emergency department or admissions to hospital per patient during the whole course of chemotherapy treatment, was evaluated with routinely available administrative healthcare data. Secondary patient reported outcomes included toxicity, self-efficacy, and quality of life. Results Baseline characteristics of participants were similar in the intervention (n=944) and control arms (n=1214); 22% were older than 65 years. Penetration (that is, the percentage of patients who received the intervention at each centre) was 50-86%. Mean number of visits to the emergency department or admissions to hospital per patient was 0.91 (standard deviation 0.28) in the intervention arm and 0.94 (0.40) in the control arm (P=0.94); 47% (1014 of 2158 patients) had at least one visit to the emergency department or a hospital admission during chemotherapy. Among 580 participants who completed the patient reported outcome questionnaires, at least one grade 3 toxicity was reported by 48% (134 of 278 patients) in the intervention arm and by 58% (163 of 283) in the control arm. No differences in self-efficacy, anxiety, or depression were found. Compared with baseline, the functional assessment of cancer therapy trial outcome index decreased by 6.1 and 9.0 points in the intervention and control participants, respectively. Conclusions Proactive, telephone based management of toxicities during chemotherapy did not result in fewer visits to the emergency department or hospital admissions. With the rapid rise in remote care because of the covid-19 pandemic, identifying scalable strategies for remote management of patients during cancer treatment is particularly relevant. Trial registration ClinicalTrials.gov NCT02485678 .

Regions of hypoxia, or low oxygen tension, are known to exist within tumours (Raleigh et al, 1996;Brown and Giaccia, 1998;Dewhirst, 1998). Since radiotherapy and some forms of chemotherapy are less effective at killing cancer cells in hypoxic environments, much effort has been directed toward identifying tumours containing such regions. Measurement of oxygen tension by needle electrodes in lymph node metastasis of cancer of the head and neck found that radiation was less effective at inducing regression when the lymph nodes were hypoxic (Gatenby et al, 1988) and such measurements have been reported to identify patients with poor locoregional tumour control (Nordsmark et al, 1996). Similar work in advanced cancer of the uterine cervix (Hockel et al, 1993(Hockel et al, , 1996Fyles et al, 1998;Hockel and Vaupel, 1998) showed that increased levels of hypoxia in the primary tumour mass correlated with poorer treatment outcome. These results suggested that hypoxia in cervical cancers correlated with a greater likelihood of both local failure and nodal metastasis. Metastases were also found to be more frequent in patients with the most hypoxic soft tissue sarcoma of the extremities (Brizel et al, 1996). Furthermore, exposure of cancer cells to hypoxia (Young et al, 1988;Jang and Hill, 1997) and hypoxia-induced increases in vascular endothelial growth factor (VEGF) secretion have been associated with an increased metastatic ability (Danielsen and Rofstad, 1998).VEGF is the most selective vascular endothelial cell mitogen known . In cancer cells, the four VEGF isoforms which have been most frequently described contain 121, 165, 189 and 206 amino acids (Tischer et al, 1991). In some studies, increased intra-tumoural VEGF mRNA and protein has been associated with poor prognosis (Berger et al, 1995;Toi et al, 1995), increased metastasis Takahashi et al, 1995), and increased microvessel density Toi et al, 1995;Fontini et al, 1997). Antibodies directed towards VEGF can inhibit angiogenesis and the proliferation of cancer cells in vivo (Kim et al, 1993;Kondo et al, 1993). Cancer cells constitutively produce VEGF and can up-regulate its expression under hypoxic stress (Shweiki et al, 1992) via the transcription factor hypoxia-inducible factor 1 (Forsythe et al, 1996) and by stabilization of the mRNA (Levy et al, 1996(Levy et al, , 1998. The qualitative relationship between oxygen level and VEGF up-regulation has been examined in a variety of different tumour systems but has not been quantitatively documented in most of the studies performed (Shweiki et al, 1992;Minchenko et al, 1994;Leith and Michelson, 1995;Mukhapadhyay et al, 1995). The purpose of the present work was to examine the relationship between VEGF mRNA level and oxygen concentration in detail and to determine the extent of its variation between different tumour cells of similar histopathological type. Cell lines derived from human cancer of the uterine cervix were chosen for the study based on the abundance of clinical data relating tumour A quantitative analysis ...