A Case Report of Bilateral Adrenal Gland Stereotactic Body Radiotherapy to Manage Hypercortisolemia in a Patient With Ectopic Adrenocorticotropic Hormone (ACTH) Production From a Metastatic Pancreatic Neuroendocrine Tumor.

A 63-year-old woman presented with hypokalemia, hypertension, weight gain, limb edema, and tremors. She was diagnosed with Cushing syndrome, with a 24-hour urine cortisol level of 41,013 nmol/day. Investigations revealed a grade 2 pancreatic neuroendocrine tumor with extensive hepatic metastases. Owing to excessive adrenocorticotropic hormone production from her disease, her hypercortisolemia and Cushing symptoms worsened despite ketoconazole, somatostatin analogs, and right liver lobe chemoembolization. Stereotactic body radiotherapy (SBRT) at a dose of 39 Gy in three fractions was administered to her bilateral adrenal glands in the hope of reducing her cortisol levels and improving her symptoms. Her 24-hour urine cortisol levels decreased following SBRT, but not rapidly enough; her clinical condition continued to deteriorate, and she died 21 days after treatment. SBRT was not effective as an urgent intervention in this setting; a greater latency to realize a response is likely necessary.

Virtual Care for Patients with Advanced Well Differentiated Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET).

INTRODUCTION: The COVID-19 pandemic resulted in an unprecedent shift towards virtual cancer care, including the care of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aim of this study was to evaluate the use of virtual care for GEP-NETs during the COVID-19 pandemic at a high-volume academic cancer center. METHODS: This retrospective, observational study performed at the Ottawa Hospital Cancer Center in Canada evaluated adult patients with GEP-NETs seen in consultation by medical oncology between 1 June 2019 and 31 December 2022. Demographic, clinicopathologic, cancer treatment and visit data were collected. Univariable and multivariable analyses assessed the relationship between patient characteristics and virtual care use. RESULTS: A total of 103 patients with well-differentiated GEP-NETS were included. Overall, 18/103 (17.5%) consults and 594/781 (76.1%) follow-ups were performed virtually. All consultation visits returned to in-person assessment by 2022, while 67.0% and 41.4% follow-ups remained virtual in 2022 and 2023, respectively. The year of follow-up, sex, employment and Charlston comorbidity index were associated with virtual follow-up use in the multivariable analysis. DISCUSSION: Virtual care remained a predominant method of GEP-NET patient assessment in the peri-pandemic period. These results highlight an opportunity to improve access to subspecialty neuroendocrine cancer care through the continued use of virtual care.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 was held in Quebec City, Quebec 2-4 February 2023. The purpose of the conference was to develop consensus statements on emerging and evolving treatment paradigms. Participants included Canadian medical oncologists, radiation oncologists, pathologists and surgical oncologists from across Ontario, Quebec, and the Atlantic provinces. Consensus statements were developed following rapid review presentations and discussion of available literature. The recommendations proposed here represent the consensus opinions of physicians involved in the care of patients with gastrointestinal malignancies who participated in this meeting.

Small Bowel Neuroendocrine Tumors-10-Year Experience of the Ottawa Hospital (TOH).

(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% (n = 91) of cases being males. The most common sites of the tumors were the ileum 53% (n = 94), followed by the duodenum 9% (n = 16) and jejunum 7% (n = 12). Approximately 24% (n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% (n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% (n = 75), and 41% (n = 73) respectively. The majority of patients 84% (n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years.

Real world use of lanreotide in neuroendocrine tumors.

Background: Treatment for metastatic neuroendocrine tumors (NETs) is often with somatostatin analogues (SSA) such as lanreotide in the first-line setting. Real world use of lanreotide in Canada is not well studied. Methods: We performed a retrospective chart review of 69 patients to study real world use of lanreotide at our centre. Results: Lanreotide was the first-line of systemic treatment in 60 patients. Watch-and-wait was a common strategy and was seen in 31 patients. SSA switch strategy was seldom applied. Majority of patients on lanreotide had low-grade NETs. Standard starting dose of lanreotide 120 mg every 28 days was used in 66 patients. Dose escalation to 120 mg every 21 days occurred in 7 patients. The primary intention for treatment was tumor control in 32 patients, and both tumor and symptom control in 34 patients. Median time on treatment was 21.6 months. Conclusions: Overall, our findings were in keeping with current guidelines. It will be interesting to assess how clinical practice evolves in the future and to determine the role of dose escalation for disease control.

Top 10 research priorities for early-stage colorectal cancer: a Canadian patient-oriented priority-setting partnership.

BACKGROUND: Colorectal cancer, one of the most commonly diagnosed cancers, is now being detected earlier and treatments are improving, which means that patients are living longer. Partnering with Canadian clinicians, patients and researchers, we aimed to determine research priorities for those living with early-stage colorectal cancer in Canada. METHODS: We followed the well-established priority-setting partnership outlined by the James Lind Alliance to identify and prioritize unanswered questions about early-stage (i.e., stages I-III) colorectal cancer. The study was conducted from September 2018 to September 2020. We surveyed patients, caregivers and clinicians from across Canada between June 2019 and December 2019. We categorized the responses using thematic analysis to generate a list of unique questions. We conducted an interim prioritization survey from April 2020 to July 2020, with patients, caregivers and clinicians, to determine a shorter list of questions, which was then reviewed at a final meeting (involving patients, caregivers and clinicians) in September 2020. At that meeting, we used a consensus-based process to determine the top 10 priorities. RESULTS: For the initial survey, 370 responses were submitted by 185 individuals; of the 98 individuals who provided demographic information, 44 (45%) were patients, 16 (16%) were caregivers, 7 (7%) were members of an advocacy group, 26 (27%) were health care professionals and 5 (5%) were categorized as "other." The responses were refined to create a list of 66 unique unanswered questions. Twenty-five respondents answered the interim prioritization survey: 13 patients (52%), 2 caregivers (8%), 3 advocacy group members (12%) and 7 health care professionals (28%). This led to a list of the top 30 questions. The final consensus meeting involved 20 individuals (10 patients [50%], 3 caregivers [15%] and 7 health care professionals [35%]), who agreed to the top 10 research priorities. The priorities covered a range of topics, including screening, treatment, recurrence, management of adverse effects and decision-making. INTERPRETATION: We determined the top research priorities for early-stage colorectal cancer using a collaborative partnership of stake-holders from across Canada. The priorities covered a broad range of topics that could be addressed by future research, including improved screening practices, the role of personalized medicine, the management of adverse effects of treatment, decision-making and prevention of recurrence.

Oral magnesium supplements for cancer treatment-induced hypomagnesemia: Results from a pilot randomized trial.

BACKGROUND AND AIMS: Optimal management of cancer treatment-induced hypomagnesemia (hMg) is not known. We assessed the feasibility of using a novel pragmatic clinical trials model to compare two commonly used oral Mg replacement strategies. METHODS: Patients with grade 1 to 3 hMg while receiving either platinum-based chemotherapy or epidermal growth factor receptor inhibitors (EGFRI) were randomized to oral magnesium oxide (MgOx) or oral magnesium citrate (MgCit). The trial methodology utilized the integrated consent model. Feasibility would be successful if; accrual rate was ≥5 patients a month and if measures of patient and physician engagement, were > 50%. Secondary endpoints included; comparison of Mg levels, cardiac arrhythmias, and rates of treatment delay/hospitalizations. RESULTS: From July 2016 to December 2017, an average of 1 patient a month was accrued. All 15 eligible and approached patients consented to participate in the study (100% engagement) and 7/15 were randomized to MgOx and 8/15 to MgCit. The percentage of physicians who approached patients for the study was 4 of 6 (66.6% engagement). The mean slope of change in Mg (mmol/L/day) was 0.0022 (95% CI: -0.0001 to 0.0044) for MgOx and 0.0006 (95% CI, -0.0012 to 0.0024) for MgCit (P = .2123). Three patients (20%) required IV magnesium while on the study (2 MgCit and 1 MgOx). Grade 1 diarrhea occurred in 3 patients in the MgCit arm. CONCLUSION: Despite oral magnesium tolerability and meeting most of its feasibility endpoints, this study did not meet its target accrual rate. Alternative designs would be necessary for a definitive efficacy study.

The Impact of Chronic Kidney Disease in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation.

BACKGROUND: Patients with chronic kidney disease are commonly excluded from clinical trials. The impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer has not been previously studied. OBJECTIVE: This study aimed to investigate the impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer. DESIGN: This is a multi-institutional, retrospective cohort study. SETTINGS: This study was conducted at academic and community cancer centers participating in the Canadian Health Outcomes Research Database Consortium Rectal Cancer Database. PATIENTS: Consecutive patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were selected. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, pathologic complete response, and neoadjuvant chemotherapy/radiotherapy completion rate were the primary outcomes measured. RESULTS: A total of 1254 patients were included. Median age was 62, and 29%/69% had clinical stage II and III disease. Median estimated creatinine clearance was 93 mL/min, with 11% <60 mL/min (n = 136). There was no significant difference in the completion rate of neoadjuvant chemotherapy (82% vs 85%, p = 0.36) or radiotherapy (93% vs 95%, p = 0.45) between patients with and without chronic kidney disease. Patients with chronic kidney disease were less likely to receive adjuvant chemotherapy (63% vs 77%, p < 0.01). On multivariate analysis, patients with chronic kidney disease had decreased disease-free survival (HR, 1.37; 95% CI, 1.03-1.82; p = 0.03) but not overall survival (HR, 1.23; 95% CI, 0.88-1.75; p = 0.23) or pathologic complete response (OR, 0.83; 95% CI, 0.50-1.39; p = 0.71). LIMITATIONS: This study was limited by its retrospective design and by limited events for overall survival analysis. CONCLUSIONS: In patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation, baseline chronic kidney disease was associated with less use of adjuvant chemotherapy and decreased disease-free survival. Chronic kidney disease was not independently associated with neoadjuvant chemotherapy/radiotherapy completion rate, pathologic complete response, or overall survival. These data suggest that patients with locally advanced rectal cancer with chronic kidney disease may have distinct outcomes and, accordingly, the results of landmark clinical trials may not be generalizable to this population. See Video Abstract at http://links.lww.com/DCR/B694. LA REPERCUSIN DE LA ENFERMEDAD RENAL CRNICA EN PACIENTES CON CNCER DE RECTO LOCALMENTE AVANZADO TRATADOS CON QUIMIORRADIOTERAPIA NEOADYUVANTE: ANTECEDENTES:Los pacientes con enfermedad renal crónica generalmente se excluyen de los ensayos clínicos. La repercusión de la enfermedad renal crónica en el desenlace en pacientes con cáncer de recto localmente avanzado no se ha estudiado previamente.OBJETIVO:Investigar la repercusión de la enfermedad renal crónica en los desenlaces en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo multiinstitucional.ESCENARIO:Centros oncológicos académicos y comunitarios que participan en la base de datos de cáncer rectal del consorcio CHORD.PACIENTES:Pacientes consecutivos con cáncer de recto localmente avanzado, tratados con quimiorradioterapia neoadyuvante, previa a la cirugía con intención curativa del 2005 al 2013.PRINCIPALES VARIABLES EVALUADAS:Sobrevida libre de enfermedad, sobrevida global, respuesta patológica completa, tasa de conclusión de quimioterapia / radioterapia neoadyuvante.RESULTADOS:Se incluyeron 1254 pacientes. El promedio de edad fue de 62, y el 29% / 69% tenían enfermedad en estadio clínico II y III, respectivamente. El promedio de la depuración de creatinina estimada fue de 93 mililitros / minuto, con un 11% <60 mililitros / minuto (n = 136). No hubo diferencias significativas en la tasa de conclusión de la quimioterapia neoadyuvante (82% vs 85%, p = 0,36) o radioterapia (93% vs 95%, p = 0,45) entre pacientes con y sin enfermedad renal crónica. Los pacientes con enfermedad renal crónica tenían menos probabilidades de recibir quimioterapia adyuvante (63% contra el 77%, p <0,01). En el análisis multivariado, los pacientes con enfermedad renal crónica tenían una sobrevida libre de enfermedad menor (HR 1,37, IC 95% 1,03-1,82, p = 0,03) pero no en la sobrevida global (HR 1,23, IC 95% 0,88-1,75, p = 0,23) o respuesta patológica completa (OR 0,83, IC 95% 0,50-1,39, p = 0,71).LIMITACIONES:Diseño retrospectivo y acontecimientos limitados para el análisis de sobrevida global.CONCLUSIONES:En pacientes con cáncer de recto localmente avanzado tratados con quimiorradioterapia neoadyuvante, la enfermedad renal crónica de base se asoció con un menor uso de quimioterapia adyuvante y una menor sobrevida libre de enfermedad. La enfermedad renal crónica no se asoció de forma independiente con la tasa de conclusión de la quimioterapia / radioterapia neoadyuvante, la respuesta patológica completa o la sobrevida global. Estos datos sugieren que los pacientes con cáncer de recto localmente avanzado con enfermedad renal crónica pueden tener resultados distintos y, en consecuencia, los resultados de los ensayos clínicos de referencia pueden no ser generalizables a esta población. Consulte Video Resumen en http://links.lww.com/DCR/B694.

Lack of neophobic responses to color in a jumping spider that uses color cues when foraging (Habronattus pyrrithrix).

Chemically defended prey often advertise their toxins with bright and conspicuous colors. To understand why such colors are effective at reducing predation, we need to understand the psychology of key predators. In bird predators, there is evidence that individuals avoid novelty-including prey of novel colors (with which they have had no prior experience). Moreover, the effect of novelty is sometimes strongest for colors that are typically associated with aposematic prey (e.g., red, orange, yellow). Given these findings in the bird literature, color neophobia has been argued to be a driving force in the evolution of aposematism. However, no studies have yet asked whether invertebrate predators respond similarly to novel colors. Here, we tested whether naive lab-raised jumping spiders (Habronattus pyrrithrix) exhibit similar patterns of color neophobia to birds. Using color-manipulated living prey, we first color-exposed spiders to prey of two out of three colors (blue, green, or red), with the third color remaining novel. After this color exposure phase, we gave the spiders tests where they could choose between all three colors (two familiar, one novel). We found that H. pyrrithrix attacked novel and familiar-colored prey at equal rates with no evidence that the degree of neophobia varied by color. Moreover, we found no evidence that either prey novelty nor color (nor their interaction) had an effect on how quickly prey was attacked. We discuss these findings in the context of what is known about color neophobia in other animals and how this contributes to our understanding of aposematic signals.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19-21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer.

BRCA mutated pancreatic cancer: A change is coming.

Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease. Recently, patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast tumors. Germline BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8% of patients with sporadic pancreatic cancer. In patients with germline BRCA mutations, platinum-based chemotherapies and poly (ADP-ribose) polymerase inhibitors are effective treatment options which may offer survival benefits. This review will focus on the molecular biology, epidemiology, and management of BRCA-mutated pancreatic cancer. Furthermore, we will discuss future directions for this area of research and promising active areas of research.

The Diminishing Importance of Primary Site Identification in Cancer of Unknown Primary: A Canadian Single-Center Experience.

BACKGROUND: Cancer of unknown primary (CUP) describes patients with metastatic disease without an identified primary tumor site. Successful diagnosis and treatment of these patients remains difficult. Published guidelines on CUP have highlighted "favorable" subtype groups. We investigated a series of CUP patients to review adherence to guidelines, and identification of primary cancers or "favorable" subtypes. METHODS: Patients with histologically confirmed CUP at an academic institution from 2012 to 2018 were identified. Patient demographics, tumor presentation, diagnostic work-up and treatment information were retrospectively collected from electronic data records for descriptive analysis and compared to published clinical guidelines. The primary endpoint was the proportion of patients where the primary site was identified. Multivariable logistic regression models were used to identify factors associated with primary site identification. Kaplan-Meier survival curves were used to determine factors associated with poorer OS. RESULTS: Three hundred and five patients were included with a median follow-up time of 4.3 months. Primary tumor sites were identified in 109 patients (37.5%), which was most commonly lung cancer (33%). Statistical analyses did not identify any demographic or initial presentation factors associated with identifying the primary or not. More diagnostic tests did not increase the likelihood of primary site identification (P=0.44). Patients with an identified primary did not have longer OS than other patients (median 5.2 months vs. 4.7 months, P=0.47). 57 patients (18.7%) who had a defined "favorable" subtype experienced superior OS (36.6 months vs. 3.8 months; P<0.0001). Further, patients with good prognostic status who followed published treatment guidelines had longer OS (17.6 months vs. 13.2 months; P=0.04). CONCLUSIONS: CUP remains a difficult cancer to diagnose and treat. These results suggest identifying the primary has less impact than anticipated, but particular efforts to identify patients with "favorable" subtypes of CUP is important prognostically.

Quality of telephone-based cancer symptom management by nurses: a quality improvement project.

PURPOSE: To determine the quality of cancer symptom management when evidence from clinical practice guidelines are used in telephone-based oncology nursing services. METHODS: Guided by the Knowledge to Action Framework, we conducted a quality improvement (QI) project focused on "monitoring knowledge use" (e.g., use of practice guides) and "measuring outcomes." In 2016, 15 Pan-Canadian Oncology Symptom Triage and Remote Support (COSTaRS) practice guides that synthesize evidence from guidelines were implemented with training for all oncology nurses at a regional ambulatory oncology program. Eighteen months post-implementation, Symptom Management Analysis Tool (SMAT) was used to analyze audio-recorded calls and related documentation of cancer symptom management. RESULTS: Of 113 audio-recorded calls, 66 were COSTaRS symptoms (58%), 43 other symptoms (38%), and 4 medically complex situations (4%). Of 66 recorded calls, 63 (95%) were documented. Average SMAT quality score was 71% (range 21-100%) for audio-recordings and 63% (range 19-100%) for documentation of calls. COSTaRS practice guide use was documented in 33% calls. For these calls, average SMAT quality scores were 74% with COSTaRS versus 69% without COSTaRS for audio-recording and 73% (range 33-100%) with COSTaRS versus 58% without COSTaRS for documentation. Patient outcomes indicated symptom was resolved (38%), worse (25%), unchanged (3%), or unknown (33%). Eight patients (13%) had an ED visit within 14 days post that was related to the symptom discussed. CONCLUSIONS: Only a third of nurses indicated use of COSTaRS practice guides. There were higher quality symptom management scores when COSTaRS use was reported. Nurses documented less than what they discussed.

Hemipteran defensive odors trigger predictable color biases in jumping spider predators.

Multimodal warning displays often pair one signal modality (odor) with a second modality (color) to avoid predation. Experiments with bird predators suggest these signal components interact synergistically, with aversive odors triggering otherwise hidden aversions to particular prey colors. In a recent study, this phenomenon was found in a jumping spider (Habronattus trimaculatus), with the defensive odor from a coreid bug (Acanthocephala femorata) triggering an aversion to red. Here, we explore how generalizable this phenomenon is by giving H. trimaculatus the choice between red or black prey in the presence or absence of defensive odors secreted from (1) eastern leaf-footed bugs (Leptoglossus phyllopus, Hemiptera), (2) grass stinkbugs (Mormidea pama, Hemiptera), (3) Asian ladybird beetles (Harmonia axyridis, Coleoptera), and (4) eastern lubber grasshoppers (Romalea microptera, Orthoptera). As expected, in the presence of the hemipteran odors, spiders were less likely to attack red prey (compared to no odor). Unexpectedly, the beetle and grasshopper odors did not bias spiders away from red. Our results with the hemipteran odors were unique to red; follow-up experiments indicated that these odors did not affect biases for/against green prey. We discuss our findings in the context of generalized predator foraging behavior and the functions of multimodal warning displays.

Quality of telephone nursing services for adults with cancer and related non-emergent visits to the emergency department.

A quality improvement project was conducted to determine the quality of telephone nursing for patients with cancer symptoms. Eligible patients were ones who telephoned the nurse about cancer symptom(s) within four weeks prior to an emergency department (ED) visit not requiring hospital admission. Experienced oncology nurses extracting data indicated appropriateness of ED visits and opportunities for improvement. The Symptom Management Analysis Tool was used to analyze nurse documentation. For 77 patients, 87% ED visits occurred within four days of calls about symptoms (e.g., pain, breathlessness, constipation, diarrhea, nausea/vomiting) and 91% could have been managed by more complete telephone assessment and/or an urgent clinic visit. Quality of nurse documentation revealed few patients were assessed adequately (38%), received any symptom-specific medication review (49%), or were guided in self-care strategies (17%). There was low-quality telephone symptom management by nurses and a need for alternative options for patients requiring urgent face-to-face assessments. Our findings highlight a gap in use of guidelines for informing telephone symptom management.

The impact of driving time, distance, and socioeconomic factors on outcomes of patients with locally advanced rectal cancer.

Objectives: Cancer patients experience disparities due to socioeconomic status (SES) factors. We assessed the impact of SES factors on outcomes in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiation (nCRT) and surgery (Sx) in 3 Canadian provinces. Study design: This study was a multi-institutional retrospective chart review. Methods: Associations among community characteristics (2016 Canadian Census data), distance and time to the cancer center (mapping software), and outcomes were evaluated using the CHORD multi-institutional database. Results: 1,064 patients were included. Median age 62, 68% male, 15% lived in a rural community, 19% with median community household income >$50,000 CAD, median community proportion with post-secondary education 66%, 12% lived >100km away, and 18% lived >1 â€‹h away.Factors predictive of worse disease-free survival (DFS) and overall survival (OS) in univariate analysis included driving time >1 â€‹h, median community income ≤$50,000 CAD, driving distance >100km, and lower median community proportion with post-secondary education. Driving time >1 â€‹h remained significant in multivariate analysis for worse DFS (HR 1.47; 95% CI 1.14-1.90; p â€‹= â€‹0.003) and OS (HR 1.60, 95% CI 1.19-2.16; p â€‹= â€‹0.002). Conclusion: Outcomes of patients with LARC undergoing nCRT are negatively associated with increased driving time to the cancer centre.

A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer.

Background Resistance to Epidermal Growth Factor inhibition (EGFRi) in patients with KRAS wild-type (wt) Colorectal Cancer (CRC) may occur as a result of PI3K/AKT/mTOR signaling. We conducted a study to establish the recommended phase II dose (RP2D) and response rate of panitumumab, an EGFRi, plus BKM120, a PI3K inhibitor, in advanced CRC. Methods Patients with chemotherapy refractory KRAS wt CRC, who were EGFRi naive were enrolled. A 3 + 3 dose escalation design was utilized. The starting dose of panitumumab was 6 mg/kg iv every 2 weeks with BKM120 at 60 mg oral daily. Results Nineteen patients were treated and 17 were evaluable for response. The starting dose was not tolerable (mucositis, fatigue). At dose level (DL) 1, three of six patients discontinued treatment due to toxicity, DL - 1 had no significant toxicity. Panitumumab 6 mg/kg iv q 2 weeks with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. One patient (5.9%) who was PTEN and PIK3CA negative by IHC had a partial response, seven had stable disease, and nine had disease progression. Conclusion Panitumumab (6 mg/kg iv q 2 weeks) with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. Toxicities including fatigue, rash and mucositis. There was little evidence of activity in this biomarker unselected cohort.

Physician-reported reasons for non-enrollment of older adults in cancer clinical trials.

OBJECTIVES: Older adults (OA) are under-represented in cancer clinical trials. We sought to identify the proportion of OA(age > 65) vs. younger adults offered clinical trial and identify reasons patients were not offered a trial. METHODS: Consecutive patients with cancer (n = 503) seen by medical oncology in consultation were included. Oncologists provided reasons for not offering a study to patients who were offered and accepted systemic therapy. Comparison between older and younger adults was done using the Chi square test or Fisher exact test. Logistic regression was used to determine the association between age and being offered clinical trial participation. RESULTS: OA had worse performance status (PS) (ECOG 3+ 15.1% vs 5.2%, p < 0.0001) and more comorbidities (Charlson Comorbidity Index ≥2 24.7% vs 10.0%, p < 0.0001) than younger adults. OA were less likely to be offered systemic treatment (68.3% vs 82.1%, p < 0.001), but were as likely as younger adults to accept (86.6% vs 92.2%, p = 0.07). Of patients who accepted systemic treatment, 24.5% were offered trial enrollment. Taking into account patient factors and stage, increased age by decade was associated with a decreased likelihood of being offered a trial [OR 0.74 (95% CI 0.6-0.9), p < 0.001]. Reasons for not offering a trial included no available trial (75.4%), poor PS (7.8%) and ineligibility (6.3%). Poor PS (11.8% vs 3.9%) was more commonly cited for not offering a study to OA. CONCLUSIONS: Lack of clinical trials is the most common reason patients are not offered a trial. OA remain less likely to be offered a trial than younger adults.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation.

BACKGROUND: A standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC. METHODS: We reviewed patients with LARC undergoing nCRT followed by surgery from 2005 to 2013 across 8 Canadian cancer centres. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for associations between baseline hematologic variables and outcomes. RESULTS: Of 1527 identified patients, 1237 (81%) were included in the DFS/OS analysis. Median age was 62 (range 23-88), 69% were male, and 80% had performance status (PS) 0-1. Twenty-six percent had elevated NLR (≥ 4), and 66% had elevated PLR (≥ 150). Ninety-seven percent of patients received FP-based nCRT, with 96% receiving ≥44 Gy. 81% completed neoadjuvant chemotherapy and 95% completed neoadjuvant radiotherapy, with a pCR rate of 18%. After a median follow-up time of 71 months, 8% developed local recurrence, 22% developed distant recurrence and 24% died. 5-year DFS and OS were 69% (95% CI 66-72%) and 79% (95% CI 77-82%), respectively. In multivariate analyses, elevated baseline NLR and PLR were neither prognostic for DFS and OS nor predictive of pCR. CONCLUSIONS: NLR and PLR were not found to be independently prognostic for DFS or OS and did not predict for pCR in patients with LARC undergoing nCRT followed by surgery.