Influence of local recurrence on survival in patients with rectal cancer

Background: Recent trials on rectal cancer have demonstrated significant improvements in local recurrence without improvements in overall survival. The aim of this paper was to define the influence of local recurrence on survival in a prospective series of patients who underwent R0 or R1 resections for rectal cancer. Methods: Patients presenting with rectal cancer from 1996 to 2012 were prospectively audited. The study included patients who underwent an R0 or R1 resection. Local recurrence was defined as cancer regrowth detected in the pelvis regardless of whether or not new metastases were found elsewhere. Kaplan–Meier curves, smoothed hazard functions and Cox models using both time since diagnosis and age as the time scale were used to define the influence of local recurrence on overall survival. Results: The study involved 483 patients, of mean age 66 years (standard deviation = 13) and a median follow-up of 5.2 years. The results at 5 years were overall survival 71% (95% confidence interval (CI) 66–75), local recurrence 7% (95% CI 5–10) and distant recurrence 18% (95% CI 14–22). Patients diagnosed with local recurrence died faster than patients diagnosed with either distant recurrence or no recurrence, and this was particularly obvious for younger patients (local hazard ratio (HR) 54, 95% CI 12–253 and distant HR19, 95% CI 4–80). Local recurrence that developed early following surgery also had worse survival outcomes. Conclusions: Within this cohort of rectal cancer patients, the early development of local recurrence was the single most important indicator of a reduced survival, and carried a worse prognosis than the development of distant metastases alone

Long-term survival following laparoscopic and open colectomy for colon cancer: a meta-analysis of randomized controlled trials

Aim: Large randomized clinical trials comparing long-term survival after laparoscopic and open colectomy for large bowel cancer show equivalence, but meaningful analysis of data by stage has not been possible due to the small numbers of patients in individual trials. The aim of this meta-analysis was to improve statistical power by combining data to enable assessment of survival for individual stages. Method: A systematic review and meta-analysis was conducted through a computerized search of all randomized controlled trials comparing open and laparoscopic surgery for large bowel cancer. Overall survival data were analysed and subgroup analysis was performed for cancer of Stages I–III. Results: Five trials (3152 patients) were included. Overall survival was equivalent (hazard ration 0.93; 95% confidence interval 0.80–1.07). With each of the cancer stages, I–III, there was no difference in 5-year survival. There was, however, a nonsignificant trend in favour of open surgery in the subgroup analysis of Stage II patients. Conclusion: Laparoscopic-assisted surgery for colon cancer is equivalent to open surgery with respect to long-term survival although there may be a difference for Stage II cancer

Locally performed postoperative circulating tumour DNA testing performed during routine clinical care to predict recurrence of colorectal cancer

Background: Identifying patients at high risk for colorectal cancer recurrence is essential for improving prognosis. In the postoperative period, circulating tumour DNA (ctDNA) has been demonstrated as a significant prognostic indicator of recurrence. These results have been obtained under the strict rigours of clinical trials, but not validated in a real-world setting using in-house testing. We report the outcomes of locally performed postoperative ctDNA testing conducted during routine clinical care and the association with the recurrence of colorectal cancer. Methods: We recruited 36 consecutive patients with newly diagnosed colorectal cancer between 2018 and 2020. Postoperative plasma samples were collected at the first outpatient review following resection. Tumour-informed ctDNA analysis was performed using droplet digital polymerase chain reaction or targeted next-generation sequencing. Results: At the time of surgery, there were 24 patients (66.7%) with localized cancer, nine (25%) with nodal spread, and three (8.3%) with metastatic disease. The median time from surgery to plasma sample donation was 22 days (IQR 20–28 days). At least one somatic mutation was identified in primary tumour tissue for 28 (77.8%) patients. Postoperative ctDNA was detected in five patients (13.9%). The median duration of follow-up was 32.0 months (IQR 27.2–38.1 months). Two patients (5.56%) developed metastatic recurrence. However, neither had detectable postoperative ctDNA. There were no instances of loco-regional recurrence. Conclusion: Analysis of postoperative ctDNA testing can be performed locally, however this study did not reproduce the adverse association between detectable postoperative ctDNA and the development of colorectal cancer recurrence seen in clinical trials

Optimizing patient risk stratification for colonoscopy screening and surveillance of colorectal cancer: The role for linked data

No abstract available for this article

K-RAS testing as part of routine care for colorectal cancer patients

Recent clinical evidence strongly suggests that only those colorectal cancer patients with wild type K-ras respond to the anti-EGFR monoclonal antibody, Cetuximab. As such K-ras mutation testing is now a pre-requisite for inclusion in forthcoming CRC clinical trials using Cetuximab and is a requirement for access through the Interim Access Program (IAP) operated by Merck. SJOG Pathology in West Australia has recently implemented K-ras mutation testing and performed 300 such tests on DNA extracted from fresh frozen material as part of creating a colorectal tissue bank within routine patient management. Approximately 32 % of cases were K-ras mutant. The results have been included in the routine histopathology report. The test is cheap and easy to perform. At the same time we have established a service for K-ras testing from archival cases using paraffin embedded samples. In contrast to the prospective cases this service has proven difficult to establish due to several reasons, the most important being that accessing archival material is relatively difficult. In addition, jurisdiction over tissue blocks and the time lapsed between the initial surgery and when the test is requested (often some years) creates significant logistical issues for sample retrieval and testing. In addition, a survey we conducted demonstrated a wide range of knowledge about the testing by oncologists and this contributed to delays in obtaining the test results. Given the increased likelihood of similar tests for other molecular markers (eg. Braf, MSI) and with an ever increasing array of targeted therapies in the pipeline we suggest that routine diagnostic pathology labs should harvest DNA from primary tumours as part of their routine practice. In this manner such tests may be optimally performed whilst at the same time avoiding double handling of samples and so reducing both the cost of and time taken to perform molecular tests

Wearable activity technology and action-planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol

Background/Objective: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical frame-work for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. Method: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12- week intervention and control groups. Intervention group participants will receive: a Fitbit AltaTM to monitor physical activity, HAPA-based group sessions, booklet, and support phone-call. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. Conclusions: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors

Promoting physical activity in regional and remote cancer survivors (PPARCS) using wearables and health coaching: Randomised controlled trial protocol

Introduction: Physically active cancer survivors have substantially less cancer recurrence and improved survival compared with those who are inactive. However, the majority of survivors (70%–90%) are not meeting the physical activity (PA) guidelines. There are also significant geographic inequalities in cancer survival with poorer survival rates for the third of Australians who live in nonmetropolitan areas compared with those living in major cities. The primary objective of the trial is to increase moderate-to-vigorous PA (MVPA) among cancer survivors living in regional and remote Western Australia. Secondary objectives are to reduce sedentary behaviour and in conjunction with increased PA, improve quality of life (QoL) in non-metropolitan survivors. Tertiary objectives are to assess the effectiveness of the health action process approach (HAPA) model variables, on which the intervention is based, to predict change in MVPA. Methods and analysis: Eighty-six cancer survivors will be randomised into either the intervention or control group. Intervention group participants will receive a Fitbit and up to six telephone health-coaching sessions. MVPA (using Actigraph), QoL and psychological variables (based on the HAPA model via questionnaire) will be assessed at baseline, 12 weeks (end of intervention) and 24 weeks (end of follow-up). A general linear mixed model will be used to assess the effectiveness of the intervention. Ethics and dissemination: Ethics approval hasbeen obtained from St John of God Hospital Subiaco (HREC/#1201). We plan to submit a manuscript of the results to a peer-reviewed journal. Results will be presented at conferences, community and consumer forums and hospital research conferences. Trial registration number: ACTRN12618001743257; pre-results, U1111-1222-569

Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response

Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3+, CD8+ and CD3+ cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response

Wearable activity technology and action-planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol

FUNDAMENTOS/OBJETIVO: Los sobrevivientes de cáncer colorrectal y ginecológico corren riesgo cardiovascular debido a las comorbilidades y al comportamiento sedentario, lo que justifica una intervención factible para aumentar la actividad física. El Enfoque del Proceso de Acción Sanitaria (HAPA) es un marco teórico prometedor para el cambio de comportamiento en materia de salud, y los rastreadores de actividad física que se pueden llevar puestos ofrecen un medio novedoso de autocontrol de la actividad física para los supervivientes de cáncer. MÉTODO: Sesenta y ocho sobrevivientes de cáncer colorrectal y ginecológico serán asignados al azar a grupos de intervención y control de 12 semanas. Los participantes del grupo de intervención recibirán: un Fitbit AltaTM para monitorear la actividad física, sesiones de grupo basadas en HAPA, un folleto y una llamada telefónica de apoyo. Los participantes del grupo de control sólo recibirán el folleto basado en HAPA. La actividad física (utilizando acelerómetros), la presión sanguínea, el IMC y las construcciones HAPA se evaluarán en la línea de base, a las 12 semanas (después de la intervención) y a las 24 semanas (seguimiento). El análisis de los datos utilizará la interacción Grupo x Tiempo de un análisis de Modelo Mixto Lineal General. CONCLUSIONES: Las intervenciones de actividad física que son aceptables y que tienen sólidos fundamentos teóricos son prometedoras para mejorar la salud de los sobrevivientes de cáncer.BACKGROUND/OBJECTIVE: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical framework for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. METHOD: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12-week intervention and control groups. Intervention group participants will receive: a Fitbit AltaTM to monitor physical activity, HAPA-based group sessions, booklet, and support phonecall. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. CONCLUSIONS: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors.• The Tonkinson Colorectal Cancer Research. Subvención 57838 • St. John of God Gynecologic Oncology Research Group (Western Australia). AyudapeerReviewe

A randomized controlled trial of Promoting Physical Activity in Regional and Remote Cancer Survivors (PPARCS).

Background Physical activity (PA) is important for cancer survivors. Trials of remotely delivered interventions are needed to assist in reaching under-served non-metropolitan cancer survivors. The objective of this study was to ascertain whether wearable technology, coupled with health coaching was effective in increasing PA in breast and colorectal cancer survivors living in regional and remote areas in Australia. Methods Cancer survivors from 5 states were randomized to intervention and control arms. Intervention participants were given a Fitbit Charge 2 and received up to 6 telephone health coaching sessions. Control participants received PA print materials. Accelerometer assessments at baseline and 12 weeks measured moderate-to-vigorous PA (MVPA), light PA, and sedentary behavior. Results Eighty-seven participants were recruited (age = 63 ± 11 years; 74 (85%) female). There was a significant net improvement in MVPA of 50 min/week, favoring the intervention group (95% confidence interval (95%CI): 13.6–86.1, p = 0.007). There was also a net increase in MVPA bouts of 39.5 min/week (95%CI: 11.9–67.1, p = 0.005), favoring the intervention group. Both groups improved light PA and sedentary behavior, but there were no between-group differences. Conclusion This is the first study to demonstrate that, when compared to standard practice (i.e., PA education), a wearable technology intervention coupled with distance-based health coaching, improves MVPA in non-metropolitan cancer survivors. The results display promise for the use of scalable interventions using smart wearable technology in conjunction with phone-based health coaching to foster increased PA in geographically disadvantaged cancer survivors