Cortinarius subgenus Leprocybe, unexpected diversity and significant differences in species compositions between western and eastern North America.

The focus of this paper is the North American species of Cortinarius in subg. Leprocybe. Eighteen species, including twelve new ones, and two tentative (aff.) species, are delimited based on morphological and molecular data (DNA ITS-LSU sequences). Existing type specimens of species in subg. Leprocybe were also studied, and neo- or epitypes designated for C. cotoneus, C. melanotus, C. phrygianus and C. venetus to stabilize the nomenclature. In addition, to improve the infrasubgeneric classification of Leprocybe three new sections are proposed: sect. Fuscotomentosi, sect. Melanoti and sect. Squamiveneti. This study adds substantial information to the knowledge of subg. Leprocybe in North America against a background of European species. To date only two species, C. phrygianus and C. squamivenetus have been reported from both continents. Citation: Ammirati J, Liimatainen K, Bojantchev D, et al. 2021. Cortinarius subgenus Leprocybe, unexpected diversity and significant differences in species compositions between western and eastern North America. Persoonia 46: 216-239. https://doi.org/10.3767/persoonia.2021.46.08.

Real-life treatment of metastatic colorectal cancer with regorafenib: a single-centre review.

BACKGROUND: Various tyrosine kinase signalling pathways affect the development and progression of colorectal cancer (crc). In clinical trials, regorafenib has been associated with a survival benefit in metastatic crc (mcrc). We assessed the safety and efficacy of regorafenib in real-world patients. METHODS: In a retrospective review of patients with mcrc treated with regorafenib at our institution from 2013 to 2015, patient demographics, treatment, and survival data were collected. Progression-free survival (pfs) and overall survival (os) were estimated using the Kaplan-Meier method. RESULTS: In total, 48 patients were offered regorafenib, and 35 (73%) started treatment. Of the patients who started regorafenib, 57% were men. Median age in the cohort was 61 years, and all patients had a performance status in the range 0-2. Time from diagnosis of mcrc to regorafenib treatment was more than 18 months in 71% of patients. Starting dose was 160 mg in 54% of the patients, 120 mg in 40%, and 80 mg in 6%. Dose reductions occurred in 34% of the patients, and interruptions, in 29%. Best response was progressive disease (60%) and stable disease (17%); response in the rest of the patients was unknown. The most common adverse events on regorafenib (any grade) were fatigue (57%), hyperbilirubinemia (43%), thrombocytopenia (37%), anorexia (31%), and hypertension (31%). The most common grade 3 or 4 adverse events were fatigue (29%), hypophosphatemia (17%), weight loss (11%), and hyperbilirubinemia (9%). Common reasons for discontinuing regorafenib included progressive disease (51%) and toxicity (26%). In patients treated with regorafenib, pfs was 2.4 months (95% confidence interval: 1.8 to 3.3 months) and os was 5.6 months (95% confidence interval: 3.7 to 8.9 months). No factors were associated with survival in univariate or multivariate analysis. CONCLUSIONS: In a real-world setting, regorafenib is associated with survival similar to that reported in the randomized controlled trials, but at the expense of toxicity leading to discontinuation in many patients. Future studies of regorafenib should focus on identifying the patients most likely to benefit and on minimizing toxicity.

Corrigendum: Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014.

[This corrects the article DOI: 10.3747/co.22.2603.].

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases 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: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23-25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer.

The role of palliative chemotherapy in hospitalized patients.

BACKGROUND: Hospitalized patients with advanced cancer often have a poor performance status, which is considered a relative contraindication to cytotoxic chemotherapy. We investigated outcomes in hospitalized solid tumour oncology patients who received palliative chemotherapy (pct). METHODS: With ethics approval, we performed a single-institution chart review of all patients hospitalized on our oncology unit who received pct between April 2008 and January 2010. Patient demographics, reasons for admission, cancer type, prior therapy, and administered chemotherapy were recorded. The primary endpoint was median survival from date of inpatient chemotherapy until death or last known follow up. We also investigated place of discharge and whether patients received additional therapy. RESULTS: During the study period, 199 inpatients received pct. Median age was 61 years; 59% of the patients were women. Most had been admitted with dyspnea (31%) or pain (29%) as the dominant symptom. Common cancers represented were breast (23%), small-cell lung cancer (sclc, 22%), non-small-cell lung cancer (nsclc, 16%), and colorectal cancer (9%). Most patients (67%) were receiving first-line chemotherapy. Median overall survival duration was 4.5 months, and the 6-month survival rate was 41%. The longest and shortest survivals were seen in the sclc and nsclc groups (7.3 and 2.5 months respectively). Factors significantly associated with shorter survival were baseline hypoalbuminemia and therapy beyond the first line. In this cohort, 77% of patients were discharged home, and 72% received further chemotherapy. CONCLUSIONS: Despite a short median survival, many patients are well enough to be discharged home and to receive further chemotherapy. The development of risk models to predict a higher chance of efficacy will have practical clinical utility.

Eastern Canadian Colorectal Cancer Consensus Conference: standards of care for the treatment of patients with rectal, pancreatic, and gastrointestinal stromal tumours and pancreatic neuroendocrine tumours.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer.

Eastern Canadian colorectal cancer consensus conference: application of new modalities of staging and treatment of gastrointestinal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Ottawa, Ontario, October 22-23, 2010. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer, such as the use of epidermal growth factor inhibitors in metastatic colon cancer, the benefit of calcium and magnesium with oxaliplatin chemotherapy, the role of microsatellites in treatment decisions for stage II colon cancer, the staging and treatment of rectal cancer, and the management of colorectal and metastatic pancreatic cancers.

Consensus recommendations for the use of anti-egfr therapies in metastatic colorectal cancer.

In January 2010, a panel of Canadian oncologists with particular expertise in colorectal cancer (crc) gathered to develop a consensus guideline on the use of therapies against the epidermal growth factor receptor (egfr) in the management of metastatic crc (mcrc). This paper uses a case-based approach to summarize the consensus recommendations developed during that meeting.These are the consensus recommendations:Testing for the KRAS status of the tumour should be performed as soon as an egfr inhibitor is being considered as an option for treatment.Anti-egfr therapies are not recommended for the treatment of patients with tumours showing mutated KRAS status.For a patient with wild-type KRAS and an Eastern Cooperative Oncology Group status of 0-2, whose mcrc has previously been treated with a fluoropyrimidine, irinotecan, and oxaliplatin, switching to an egfr inhibitor is a recommended strategy.Cetuximab, cetuximab plus irinotecan, and panitumumab are all options for third-line therapy in patients with wild-type KRAS, provided that tolerability is acceptable.

Eastern Canadian Colorectal Cancer Consensus Conference: setting the limits of resectable disease.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, October 22-24, 2009. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management colorectal cancer, such as the management of hepatic and pulmonary metastases, the role of monoclonal antibodies to the epidermal growth factor receptor, and the benefits and safety of chemotherapy in elderly patients. The management of gastrointestinal neuroendocrine tumours and gastric cancer are also discussed.

Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer.

QUESTION: What are the benefits associated with the use of anti-epidermal growth factor receptor (anti-EGFR) therapies in squamous cell carcinoma of the head and neck (HNSCC)? Anti-EGFR therapies of interest included cetuximab, gefitinib, lapatinib, zalutumumab, erlotinib, and panitumumab. PERSPECTIVES: Head-and-neck cancer includes malignant tumours arising from a variety of sites in the upper aerodigestive tract. The most common histologic type is squamous cell carcinoma, and most common sites are the oral cavity, the oropharynx, the hypopharynx, and the larynx. Worldwide, HNSCC is the sixth most common neoplasm, and despite advances in therapy, long-term survival in HNSCC patients is poor. Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced (stages III-IVB) HNSCC; however, meta-analytic data indicate that the benefit of concurrent platinum-based chemotherapy disappears in patients over the age of 70 years. Cetuximab is a monoclonal antibody approved for use in combination with radiation in the treatment of patients with untreated locally advanced HNSCC and as monotherapy for patients with recurrent or metastatic (stage IVC) HNSCC who have progressed on platinum-based therapy. Given the interest in anti-EGFR agents in advanced HNSCC, the Head and Neck Cancer Disease Site Group (DSG) of Cancer Care Ontario's Program in Evidence-Based Care (PEBC) chose to systematically review the literature pertaining to this topic so as to develop evidence-based recommendations for treatment. OUTCOMES: Outcomes of interest included overall and progression-free survival, quality of life, tumour response rate and duration, and the toxicity associated with the use of anti-EGFR therapies. METHODOLOGY: The medline, embase, and Cochrane Library databases, the American Society of Clinical Oncology online conference proceedings, the Canadian Medical Association InfoBase, and the National Guidelines Clearinghouse were systematically searched to locate primary articles and practice guidelines. The reference lists from relevant review articles were searched for additional trials. All evidence was reviewed, and that evidence informed the development of the clinical practice guideline. The resulting recommendations were approved by the Report Approval Panel of the PEBC, and by the Head and Neck Cancer DSG. An external review by Ontario practitioners completed the final phase of the review process. Feedback from all parties was incorporated to create the final practice guideline. RESULTS: The electronic search identified seventy-four references that were reviewed for inclusion. Only four phase iii trials met the inclusion criteria for the present guideline. No practice guidelines, systematic reviews, or meta-analyses were found during the course of the literature search. The randomized controlled trials (RCTS) involved three distinct patient populations: those with locally advanced HNSCC being treated for cure, those with incurable advanced recurrent or metastatic HNSCC being treated with first-line platinum-based chemotherapy, and those with incurable advanced recurrent or metastatic HNSCC who had disease progression despite, or who were unsuitable for, first-line platinum-based chemotherapy. PRACTICE GUIDELINE: These recommendations apply to adult patients with locally advanced (nonmetastatic stages iii-ivb) or recurrent or metastatic (stage IVC) HNSCC. Platinum-based chemoradiation remains the current standard of care for treatment of locally advanced HNSCC. In patients with locally advanced HNSCC who are medically unsuitable for concurrent platinum based chemotherapy or who are over the age of 70 years (because concurrent chemotherapy does not appear to improve overall survival in this patient population), the addition of cetuximab to radical radiotherapy should be considered to improve overall survival, progression-free survival, and time to local recurrence.Cetuximab in combination with platinum-based combination chemotherapy is superior to chemotherapy alone in patients with recurrent or metastatic HNSCC, and is recommended to improve overall survival, progression-free survival, and response rate.The role of anti-EGFR therapies in the treatment of locally advanced HNSCC is currently under study in large randomized trials, and patients with HNSCC should continue to be offered clinical trials of novel agents aimed at improving outcomes. QUALIFYING STATEMENTS: Chemoradiation is the current standard of care for patients with locally advanced HNSCC, and to date, there is no evidence that compares cetuximab plus radiotherapy with chemoradiation, or that examines whether the addition of cetuximab to chemoradiation is of benefit in these patients. However, five ongoing trials are investigating the effect of the addition of EGFR inhibitors concurrently with, before, or after chemoradiotherapy; those trials should provide direction about the best integration of cetuximab into standard treatment. In patients with recurrent or metastatic HNSCC who experience progressive disease despite, or who are unsuitable for, first-line platinum-based chemotherapy, gefitinib at doses of 250 mg or 500 mg daily, compared with weekly methotrexate, did not increase median overall survival [hazard ratio (hr): 1.22; 96% confidence interval (ci): 0.95 to 1.57; p = 0.12 (for 250 mg daily vs. weekly methotrexate); hr: 1.12; 95% ci: 0.87 to 1.43; p = 0.39 (for 500 mg daily vs. weekly methotrexate)] or objective response rate (2.7% for 250 mg and 7.6% for 500 mg daily vs. 3.9% for weekly methotrexate, p > 0.05). As compared with methotrexate, gefitinib was associated with an increased incidence of tumour hemorrhage (8.9% for 250 mg and 11.4% for 500 mg daily vs. 1.9% for weekly methotrexate).

The duration of fecal Salmonella shedding following clinical disease among dairy cattle in the northeastern USA.

The objectives of this study were to determine the duration of fecal Salmonella shedding among dairy cattle in the northeastern United States following laboratory-confirmed clinical disease and to evaluate whether age group or serotype was associated with either shedding period or mortality. Study farms included 22 dairy herds that had at least two previous salmonellosis cases confirmed by fecal culture. Veterinarians continued to submit culture samples from clinical suspects following herd enrollment, and fecal samples from positive cattle were collected monthly until three sequential negative results were obtained or until loss to follow-up. There were 357 culture-positive clinical cases that each involved a single serotype during the shedding period. The Kaplan-Meier median duration of fecal Salmonella shedding was 50 days, and the maximum was 391 days. S. Newport was the predominant serotype, accounting for 51% of the cases. Age group and serotype were not significant predictors of Salmonella shedding duration in a Cox proportional hazards model, when stratifying by herd. However, the proportion of adult cows shedding for at least two consecutive monthly samples was significantly greater than the proportion of female calves shedding for this duration (Fisher's exact test p-value<0.01). Age group was also associated with mortality in this study; calves with salmonellosis were more likely to die than cows as estimated by a logistic regression model which controlled for herd as a random effect (p-value=0.04).

The incidence of salmonellosis among dairy herds in the northeastern United States.

The objectives of this study were to estimate the incidence of salmonellosis among a large sample of dairy herds in the northeastern United States (both at the animal level and the herd level), to describe the serotypes and antimicrobial resistance profiles of the positive samples, and to determine whether various herd-level factors were important predictors of incidence. Participating veterinarians enrolled 831 dairy herds and submitted fecal samples from 2,565 female dairy cattle for Salmonella culture because of suspicion of clinical disease. Estimates of animal-level incidence rates were calculated for each age group as the number of cases per animal time at risk, and an estimate of herd-level incidence rate was calculated as the number of positive herds per herd time at risk. Descriptive analysis of serotype data and level of antimicrobial resistance was performed, and Poisson regression analysis was used to study associations between the within-herd incidence of salmonellosis and certain predictor variables (herd size, housing type, vaccination status, and prior history of Salmonella infection). Salmonella was isolated from 576 (22.5%) samples representing 93 herds. The animal-level incidence rates for preweaned female calves, heifers, and adult cows were 8.1, 0.04, and 1.8 cases per 1,000 animal-years, respectively. The herd-level incidence rate was 8.6 positive herds per 100 herd-years. Salmonella Newport was the predominant serotype, accounting for 41% of the cases, followed by Salmonella Typhimurium. Over 68% of all isolates were resistant to 5 or more antimicrobial agents. Herd size was the only significant predictor of the incidence of salmonellosis in a multivariable model; herds with at least 400 female dairy cattle had a higher incidence rate than smaller herds. Our results shed light on the impact of salmonellosis on the dairy industry in the northeastern United States, and they help clarify the role of dairy cattle as a source of Salmonella serotypes that are also important human pathogens.

Canadian supportive care recommendations for the management of neutropenia in patients with cancer.

Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined.

Canadian supportive care recommendations for the management of anemia in patients with cancer.

Anemia is a common finding in cancer patients, most often as a result of chemotherapy. Management of anemia requires a comprehensive approach of appropriate diagnosis, exclusion of reversible causes, use of erythropoiesis-stimulating agents (ESAS), and iron supplementation. Recently, consensus guidelines on the management of chemotherapy-induced anemia were published in Europe and the United States. The present review is intended to be a practical guide for Canadian physicians, based on published guidelines, but specifically tailored to the Canadian environment. Recommendations for the use of ESAS are presented, including initiation, target hemoglobin, dosing and adjustments, monitoring, and re-initiation. Issues of safety are also addressed, including thromboembolic risk, impact on survival, and tumour progression. The importance of iron metabolism and the use of iron supplementation (both oral and parenteral) is discussed.

A National Cancer Institute of Canada Clinical Trials Group Study--IND.135: Phase I/II study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer.

Thirty-one patients with metastatic colorectal cancer were enrolled in this phase I/II trial of a triple combination of camptosar (C), oxaliplatin (O) and tomudex (T), all given on day one of a convenient three-week schedule. Patients received 257 cycles (1-18) in five cohorts. Toxicity was manageable and haematological toxicity was mild to moderate. Diarrhoea was the main dose-limiting toxicity; nausea and vomiting were common. Fatigue was frequent, moderate in severity and a reason for discontinuation in some patients. The recommended phase II doses were (C) 220 mg/m(2), (O) 100mg/m(2), (T) 2.75 mg/m(2). A 50% response rate in 30 evaluable patients was confirmed by an independent radiology review board; progression-free survival and overall median survival were 7.3 months and 16.6 months, respectively. Of the 16 patients treated at the recommended dose, 9 (56.3%) experienced partial response. Further evaluation in a randomized study compared to sequential doublets is warranted. Triple combinations could be relevant in curative settings for high-risk patients.

A phase I study of AMD473 and docetaxel given once every 3 weeks in patients with advanced refractory cancer: a National Cancer Institute of Canada-Clinical Trials Group trial, IND 131.

BACKGROUND: AMD473 (previously ZD0473) is a new-generation platinum compound with activity against a wide range of human tumour cell lines and xenografts, including carboplatin- and cisplatin-resistant lines. To assess its potential combined with a taxane, a phase I study of AMD473 and docetaxel in advanced cancer was initiated by the National Cancer Institute of Canada-Clinical Trials Group. PATIENTS AND METHODS: Patients with advanced cancer, measurable disease, performance status Eastern Cooperative Oncology Group 0-2, no major organ dysfunction, and one or no previous taxane regimen received escalating doses of AMD473 and docetaxel every 3 weeks, with a starting dose of AMD473 80 mg/m(2) and docetaxel 60 mg/m(2). RESULTS: Thirty-three patients enrolled on four dose levels were evaluable for toxicity and 25 patients were evaluable for response. The maximum tolerated dose was dose level 4 (AMD473 120 mg/m(2) and docetaxel 75 mg/m(2)), with grade 4 neutropenia in both minimally and heavily pretreated patients causing dose-limiting toxicity. As well at dose level 4, one patient had grade 3 vomiting despite premedication. Dose level three was expanded for both groups of patients and was defined as the recommended phase II dose at AMD473 100 mg/m(2) and docetaxel 75 mg/m(2). Non-hematologic toxicities included fatigue, diarrhoea and other mild toxicities. There was one partial response in a patient with prostate cancer and stable disease in 15 patients. No apparent pharmacokinetic interaction was noted. CONCLUSION: AMD473 and docetaxel can be combined with a recommended phase II dose level of 100 mg/m(2) and 75 mg/m(2), respectively, given intravenously every 3 weeks. The combination has activity and should be explored in responsive tumour types.

A National Cancer Institute of Canada clinical trials group phase II study of eniluracil (776C85) and oral 5-fluorouracil in patients with advanced squamous cell head and neck cancer.

UNLABELLED: BACKGROUND/PATIENTS AND METHODS: Thirty-two patients with recurrent head and neck cancer (HNC) following radiotherapy and/or surgery were treated with eniluracil (10 mg/m2) and 5-fluorouracil (5-FU) (1 mg/m2) (E5F) orally twice daily for 28 days followed by a seven-day treatment free period. Thirty-five-day cycles were repeated until disease progression, unacceptable toxicity or patient refusal. Doses were modified for toxicity. Standard toxicity and response criteria were used. RESULTS: Thirty-two patients were accrued; thirty-two and twenty-eight patients were evaluable for toxicity and response, respectively. Twelve patients received three or more cycles of E5F. Drug related toxicities were usually grade 1-2 intensity and included lethargy, nausea or diarrhea (> or = 25% of patients), and anorexia, rash or itch, stomatitis or vomiting (12%-24% of patients). Hematologic toxicity was generally mild; two patients experienced grade 3-5 leukopenia or thrombocytopenia. No significant biochemical toxicity was seen. One patient was withdrawn (severe nausea and vomiting) and one patient died because of drug related toxicity (thrombocytopenia). In the final analysis there were one complete and four partial responses for a 15.6% overall response. CONCLUSIONS: E5F demonstrates activity in chemotherapy naïve patients with advanced HNC cancer with acceptable toxicity profile. Further investigation of E5F with other active agents is warranted in HNC.