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.

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.

Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer.

PURPOSE: To determine whether the addition of infusional fluorouracil (I-FU) to standard radiotherapy improves survival at acceptable toxicity in patients with locally advanced squamous cell head and neck cancer (SCHNC). PATIENTS AND METHODS: Consenting patients with an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2; with stage III or IV SCHNC of the oral cavity, oropharynx, hypopharynx, or larynx; and who were recommended for radiotherapy with curative intent received 66 Gy of radiation therapy delivered in 2-Gy fractions once daily 5 days per week for 6 1/2 weeks. Those in the experimental arm received I-FU 1.2 g/m2/d, as a 72-hour infusion in the first and third weeks of radiation. Saline infusions were used in the placebo arm. RESULTS: One hundred seventy-five patients were randomized (88 to I-FU and 87 to placebo), and the treatment arms were well balanced. The complete response rate was 68% for I-FU and 56% for placebo (P = .04). The overall median survival duration was 33 months for I-FU and 25 months for placebo (P = .08). Progression-free survival also favored I-FU (P = .06). Toxicity was greater in I-FU patients, but did not interfere with the scheduled delivery or completion of radiation. CONCLUSION: The addition of I-FU to standard radiation in SCHNC improved the complete response rate and was associated with beneficial trends in progression-free and overall survival compared with radiation alone. I-FU patients also experienced greater morbidity, but this did not compromise delivery of radiotherapy.

The Head and Neck Radiotherapy Questionnaire: a morbidity/quality-of-life instrument for clinical trials of radiation therapy in locally advanced head and neck cancer.

PURPOSE: The purpose of this study was to develop and validate an instrument for clinical trials to measure radiation-related acute morbidity and quality of life from the perspective of patients with head and neck cancer (HNC) treated with radiotherapy. METHODS: The Head and Neck Radiotherapy Questionnaire (HNRQ) was developed by a panel of health care workers and patients, was pretested in a pilot study of HNC patients, and was validated in a randomized double-blind trial of concomitant fluorouracil (FUra) infusional therapy (1.2 g/m2 per 24 hours) or saline placebo administered for 72 hours in the first and third weeks of a 6 1/2-week course of radiation therapy. The HNRQ was validated against existing toxicity and performance status indices, all of which were measured weekly for the 6 1/2 weeks of treatment and for 4 weeks posttreatment. RESULTS: There were three a priori constructs: (1) that the HNRQ scores would conform to a shallow U-shaped pattern to reflect declining quality of life (increasing morbidity) during radiation and recovery posttreatment; (2) that the HNRQ would correlate with existing toxicity indices (World Health Organization [WHO] stomatitis, Byfield stomatitis, WHO skin toxicity, Eastern Cooperative Oncology Group [ECOG] and Karnofsky performance status); and (3) that the HNRQ would discriminate between FUra and placebo groups. The HNRQ and its domain scores all showed a change from baseline reflecting increased morbidity during radiation (analysis of variance [ANOVA], P < .00001). The HNRQ correlated well with all other indices (r > or = .60), and domain scores correlated best with other indices that assess the same symptom complex (eg, HNRQ skin domain and WHO skin toxicity index, r = .77). There was a significant difference in HNRQ scores between the FUra and placebo groups during radiation (ANOVA, P = .0007), and all HNRQ domains also discriminated between the treatment groups. CONCLUSION: The HNRQ is a valid measure of acute morbidity due to radiation therapy in patients with locally advanced HNC, and may be useful as an outcome measure for future clinical trials of radiation treatment strategies.

A randomized comparison of cyclophosphamide-mitoxantrone-5-fluorouracil v cyclophosphamide-doxorubicin-5-fluorouracil in advanced breast cancer: preliminary observations.

Forty-four patients with measurable metastatic breast cancer have been entered in a randomized study comparing mitoxantrone to doxorubicin as a component of front-line combination chemotherapy. Patients were stratified according to whether or not they had previously received adjuvant chemotherapy. Initial doses of cyclophosphamide and 5-fluorouracil were 500 mg/m2 for both regimens, with either mitoxantrone, 10 mg/m2, or doxorubicin, 50 mg/m2. All drugs were given on day 1 only, with treatments repeated every 3 weeks. Doses were adjusted according to blood count nadirs. Responses have been observed in both of the treatment groups, though it is too early to determine the relative efficacy of the two regimens. Toxicity was comparable on the two treatment regimens except that far less alopecia and stomatitis were associated with the mitoxantrone therapy. No congestive heart failure has been seen. The combination of cyclophosphamide-mitoxantrone-5-fluorouracil is reasonably well tolerated, with myelosuppression being dose limiting. In both treatment groups of this study, reliance on the leucocyte count, rather than the granulocyte count, as a basis for dose alteration or treatment delay would lead to excessive dose reductions, many fewer dose escalations, and much more treatment delay.

Concurrent use of multiple low dose chemotherapy agents with differing mechanisms of action as a strategy vs passive resistance: A pilot study.

Resistance may be classified as active (or competitive) (due to excess amount of a factor) vs passive (or non-competitive) (due to a deficiency of a factor). Passive resistance may be important in human solid tumors. In passive resistance, the dose-response curve may be shallow, or may flatten at a relatively low dose. We hypothesized that, if passive resistance were important, it might be advantageous to use low doses of multiple concurrent chemotherapy agents with differing mechanisms of action, rather than using high doses of 2 or 3 drugs. We combined single day cisplatin 60 mg/m2, cyclophosphamide 250 mg/m2, epirubicin 40 mg/m2, paclitaxel 60 mg/m2, and vinblastine 2.5 mg/m2, with 5 days of 5-fluorouracil 200 mg/m2, folinic acid 20 mg/m2 and dexamethasone 4 mg orally q.i.d. every 3 weeks. In later cohorts, doses were escalated, and tamoxifen and verapamil were added. Twenty-three patients were entered. ECOG performance status was 1 in 15 patients and 2 in 8. Number of prior chemotherapy regimens was 0 in 4 patients, 1 in 4, 2 in 8, 3 in 4, 4 in 2, and 7 in 1. Sixteen patients had prior radiotherapy, and 3 had no prior therapy. Myelosuppression and febrile neutropenia were frequent, and 4 heavily pretreated patients died of pneumonia contracted while neutropenic. Diarrhea, nausea and vomiting, and fatigue were also prominent. Among 9 patients with non-small cell lung cancer, one had a partial remission, 4 had stable disease (including 3 with minor objective responses). Two additional non-small cell lung cancer patients also had objective tumor regression, but were coded as failures, since one had tumor progression in <6 weeks and the other died of respiratory failure (thought to be due to severe mucous plugging) one week after his first course of treatment. Among 14 patients with other tumor types, there was one partial response (esophageal carcinoma), 6 patients with stable disease for >6 weeks (including minor responses in one patient each with adenocarcinomas of kidney and breast), and 7 failures (including one patient with adenocarcinoma unknown primary who had minor tumor regression lasting 4 weeks). Despite the unacceptably high toxic death rate, median survival time was 24 weeks (range, 1 week to >104 weeks). This regimen is toxic, but survival duration is longer than would be expected in this heavily pre-treated population. Doses recommended for further study are those used in the first treatment cohort (as described above). Since myelosuppression is the major toxic effect, hemopoietic growth factors might prove helpful with this regimen.

A case of a Ki-1 large cell anaplastic lymphoma with ultrastructural features.

A 29-year-old woman first presented in 1982 with a large cell lymphoma, initially thought to be of histiocytic origin on the basis of prominent sinus infiltration. She had a complete response to chemotherapy, but relapsed in 1987. Histologically, a repeat biopsy was identical to the first. Immunocytochemically, there was strong reactivity with Ki-1 antibody and histiocyte lineage markers, but all specific T cell markers were negative. Southern blot hybridization demonstrated a clonally rearranged band with the T cell receptor (T beta) probe. Ultrastructurally, the cells showed sparse organelles except for prominent paranuclear Golgi apparatus, frequent reniform nuclear indentations, and ruffled cytoplasmic membranes. This case appears to represent a Ki-1-positive lymphoma with the hybrid features of an activated T lymphocyte and a histiocyte.

Methotrexate and 5-fluorouracil in the treatment of squamous and other carcinomas of the head and neck.

Thirty-two patients with squamous cell carcinomas of the head and neck and three patients with parotid gland carcinomas were treated with methotrexate 40 mg/m2 followed 1 h later by 5-fluorouracil 600 mg/m2. Treatments were repeated on day 8, then every 2 weeks, toxicity permitting. Of 30 evaluable patients with squamous cell carcinomas, 9 (30%) achieved a partial (8) or complete (1) remission. Performance status and prior treatment history appeared to affect the probability of response. The original site of the primary had no apparent effect on response rate. Six patients having objective tumor regression but less than the amount required for classification as partial remission all had marked symptomatic relief and had "response" durations and survivals quite comparable to those in patients achieving partial remission. One patient with a parotid gland carcinoma attained a complete remission, one had a minor response, and one refused to return for follow-up. Myelosuppression and stomatitis were dose-limiting in some patients, although the regimen was generally well tolerated. Three patients (9%) developed cerebellar toxicity, suggesting that prior ethanol abuse could possibly predispose to this side effect.

Multicenter phase II trial of brequinar sodium in patients with advanced squamous-cell carcinoma of the head and neck.

A total of 19 patients with advanced squamous-cell carcinoma of the head and neck who had not previously been exposed to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given intravenously at a median weekly dose of 1,200 mg/m2. The toxicity was moderate, with 7 patients (37%) experiencing grade 3 or 4 toxicity. In all, 16 patients who were evaluable for efficacy showed no objective response. We conclude that brequinar given at this dose and on this schedule has no significant activity in advanced squamous-cell carcinoma of the head and neck.

Phase II study of high-dose mitoxantrone in the treatment of recurrent squamous cell carcinoma of the head and neck.

Sixteen consenting patients with squamous-cell carcinoma of the head and neck recurrent after surgery and irradiation were treated with i.v. mitoxantrone. The mitoxantrone dose given to most patients was 16 mg/m2. Two patients older than 70 years old and one performance status 3 patient received a slightly lower dose (14 mg/m2). Two patients who died less than 3 weeks after treatment were considered unevaluable for response. Of the 14 evaluable patients, eight (57%) were stable (including three with tumor shrinkage less than 50%) and six (43%) failed. There were no major responses. Most treatment courses resulted in granulocytopenia, but this was rapidly reversible and not associated with major infections. Other toxicity was generally mild to moderate. Based on this study, we conclude that mitoxantrone has minimal activity against squamous-cell carcinoma of the head and neck. Studies of the drug in other tumor types at doses of 16 mg/m2 or higher may be warranted.