Purpose To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer. Methods Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. Results Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required. Recommendations It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .

No abstract

Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 pg Ni/ml for particulate nickel compounds and 45 to 60 pg Ni/ml for water-soluble salts (NiCI2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 pg Ni/ml), while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 pg Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of -1:1.5 to 1:5 (except -1:20 for nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 1 0-fold range in cytoplasmic and nuclear nickel concentrations, [Nil. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Nil); water-soluble salts (very low nuclear [Nil; high cytosolic [Nil), and slightly soluble compounds (relatively high cytosolic and nuclear [Nil). Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds. -Environ Health Perspect 1 02(Suppl 3): 69-79 (1994).

These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung metastases should be seen in consultation with a thoracic surgeon. Combined or staged metastasectomy is recommended when, taking into account anatomic and physiologic considerations, the assessment is that all pulmonary metastases can also be completely removed. Furthermore, liver resection may be indicated in patients who have had a prior lung resection, and vice versa. 1(b). Routine liver resection is not recommended in patients with portal nodal disease. This group includes patients with radiologically suspicious portal nodes or malignant portal nodes found preoperatively or intraoperatively. Liver plus nodal resection, together with perioperative systemic therapy, may be an option-after a full discussion with the patient-in cases with limited nodal involvement and with metastases that can be completely resected. 1(c). Routine liver resection is not recommended in patients with nonpulmonary ehms. Liver plus extrahepatic resection, together with perioperative systemic therapy, may be an option-after a full discussion with the patient-for metastases that can be completely resected. 2(a). Perioperative chemotherapy, either before and after resection, or after resection, is recommended in patients with resectable ABSTRACT Questions1. Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? 2. What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy ("conversion")? 3. What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? PerspectivesAdvances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%-10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. MethodologyRecommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on th...

PURPOSE To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline. METHODS An Expert Panel conducted a systematic review to identify new, potentially practice-changing data. RESULTS Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations. RECOMMENDATIONS Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer. Additional information can be found at www.asco.org/breast-cancer-guideline .

The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was “What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?”A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint.Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine therapy, and targeted therapy for her2-positive disease are reported in separate articles in this supplement. The full three-part 1-21 evidence-based series, including complete details of the development and consensus processes, can be found on the Cancer Care Ontario Web site at https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs.

Introduction 2.2 Physical state 2 Determinant factors in the biological chemistry and Solids are the most commonly encountered forms of metals toxicology of the elements and metalloids in human respiratory exposures. Particle size 2.1 Introductory comment determines what can be inhaled and where in the respiratory 2.2 Physical state tract particles penetrate and are deposited, while particle 2.3 Atomic properties surface activity and solubility influence the extent and rate of 2.4 Determinants of reactivity absorption of its constituents by the lung or by the gastrointes-2.4.1 Ionic and covalent bonding tendencies and donor-atom tinal (GI ) tract. As shown later, these properties can also preference mediate the type and degree of tissue injury on contact. 2.4.2 Metal-ion complex formation and stability Under standard conditions (25 °C and 101.3 kPa), very few 2.4.3 Kinetic aspects compounds of metals and metalloids are liquids. Exceptions 2.4.4 Solubility are mercury metal, nickel tetracarbonyl, certain alkyl deriva-2.4.5 Speciation of the elements tives of, for example, lead, mercury and tin and chlorides of 2.4.6 Radical formation arsenic and germanium. If not contained, such liquids release 2.4.7 Particle size and shape vapours, which in most cases are extremely toxic.2,3 Vapours 2.4.8 Physico-chemical properties of solid surfaces can also arise from solids by sublimation, of which arsenic 2.5 Biological factors trioxide (Á193 °C ) is an example. 2.5.1 Compartmentalization Gases are common forms of compounds that have as 2.5.2 Respiratory tract deposition and clearance components the lighter elements (e.g., N, O, S, halogens) and 2.5.3 Bioavailability and uptake some elements with high atomic masses such as As, Sb and 2.5.4 Biological turnover time and bioaccumulation Se. Obviously the most frequently encountered environmental 2.5.5 Tolerance and susceptibility gaseous pollutants are included in the former group, namely 3 Conclusion sulfur dioxide, ozone, carbon monoxide, carbon dioxide and nitrogen oxides. Gases penetrate deep into the lungs unless

Virtual care in cancer care existed in a limited fashion globally before the COVID-19 pandemic, mostly driven by geographic constraints. The pandemic has required dramatic shifts in health care delivery, including cancer care. We conducted a systematic review of comparative studies evaluating virtual versus in-person care in patients with cancer. Embase, APA PsycInfo, Ovid MEDLINE, and the Cochrane Library were searched for literature from January 2015 to 6 August 2020. We adhered to PRISMA guidelines and used the modified GRADE approach to evaluate the data. We included 34 full-text publications of 10 randomized controlled trials, 13 non-randomized comparative studies, and 5 ongoing randomized controlled trials. Evidence was divided into studies that provide psychosocial or genetic counselling and those that provide or assess medical and supportive care. The limited data in this review support that in the general field of psychological counselling, virtual or remote counselling can be equivalent to in-person counselling. In the area of genetic counselling, telephone counselling was more convenient and noninferior to usual care for all outcomes (knowledge, decision conflict, cancer distress, perceived stress, genetic counseling satisfaction). There are few data for clinical outcomes and supportive care. Future research should assess the role of virtual care in these areas. Protocol registration: PROSPERO CRD42020202871.