Presentation and Outcome of Patients with Multiple Myeloma (MM), Single Centre Experience from Windsor Essex Regional Cancer Centre.

Introduction: Outcomes for patients with multiple myeloma has significantly improved through the years. This is mainly related to the use of novel agents. Methods: This is a retrospective study that reviewed presentation and outcome of 139 patients with multiple myeloma at the Windsor Essex Regional Cancer Centre from Jan. 1, 2015 to Dec. 31, 2019. Median age was 71 years and most patients had higher risk disease (65.5% either R ISS stage II or III). 30% had high risk FISH for myeloma including del.17P, t (4:14), t (14:16) and Gain (1q21). In terms of presentation, 38.8% had anemia (hemoglobin <100g/L), 18.7% had hypercalcemia, 74.1% had skeletal lytic lesions, 38.8% had pathologic fracture and 17.3% had plasmacytoma. Results: Almost all (92%) of the patients were treated using at least one novel agent (proteasome inhibitor or immunomodulators [ImiDs]). Cyclophosphamide, bortezomib, and dexamethasone (CyBorD) was the most used treatment regimen (48.9%) followed by bortezomib, melphalan and prednisone (BMP) at 28.8% and lenalidomide, dexamethasone (LenDex) at 14.4%. With respect to response to therapy, 51.8% had at least Very good partial response (VGPR), while 9.4% had progressive disease. 33% had autologous stem cell transplant. After a median follow up of 2.4 years, median overall survival was 3.7 years. 2 years overall survival and relapse-free survival were 70% and 83%, respectively. Discussion: Our study showed comparable outcome for patients with multiple myeloma despite older age and higher risk disease. Outcome is expected to improve with the introduction of more novel agents.

Vitamin D deficiency in patients with diabetes and its correlation with water fluoride levels.

Chronic exposure to fluoride through drinking water has been linked to insulin resistance and resulting type 2 diabetes mellitus (T2DM). Here, we aim to study the impact of water fluoride levels on blood glucose and vitamin D levels. A hospital-based study was conducted on diabetic patients (n = 303) at All India Institute of Medical Sciences (AIIMS), Raebareli outstation patient department (OPD). The relationship between vitamin D or fasting blood glucose levels (BGLs) with water fluoride levels was estimated through Spearman's rank correlation. We found a significant negative correlation between water fluoride and vitamin D levels [rs = -0.777, p-value < 0.001] and a positive correlation between water fluoride and fasting BGLs [rs = 0.178, p-value <0.05]. The participants residing in fluoride-endemic areas (F > 1.5 mg/L) had higher odds of severe vitamin D deficiency (odds ratio: 5.07, 95% CI: 1.9-13.2, p-value = 0.0009). The results demonstrate that vitamin D deficiency and fasting BGLs are significantly associated with water fluoride levels. This study signifies the role of fluoride toxicity in poor glycemic control and derived vitamin D deficiency. Vitamin D supplementation and the application of standard household water purification devices are recommended to tackle vitamin D deficiency in fluoride-endemic areas.

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer.

Addition of platinums to combination chemotherapy for triple negative breast cancer (TNBC) has shown efficacy and is increasingly accepted in the clinic, yet optimal delivery is unknown. A prospective clinical trial with TNBC patients was conducted to determine the optimal chemotherapy regimen to deliver carboplatin with standard dose dense ACT. Tissue microarray was conducted to isolate markers indicative of response to treatment. 90 TNBC patients were enrolled onto our trial. The most successful version placed the carboplatin on the second and final paclitaxel treatment with liberal hematological parameters. Our final regimen had the lowest grade 3 or 4 toxicities, no delays, no dose reductions of carboplatin, and 32% reduction in paclitaxel doses. Stage I (AJCC7) patients did well with carboplatin-based chemotherapy with zero relapse rate. Reduction in protein levels of androgen receptor and PD-L1 were found to be potential indicators of patient relapse. We have optimized a protocol for the addition of carboplatin to standard of care chemotherapy in TNBC patients. Early data indicates reduced protein levels of androgen receptor and PD-L1 as indicators of response to treatment.Trial registration This trial was registered at Canadian Cancer Trials. http://www.canadiancancertrials.ca/.

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline.

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 .

Survival of patients with pancreatic cancer treated with varied modalities: A single-centre study.

The present retrospective chart review examined the overall survival (OS) of patients with pancreatic ductal adenocarcinoma based on the disease stage in a sample of 296 patients with pancreatic cancer. Secondary outcome measurements included OS in chemotherapy vs. supportive treatment groups among metastatic patients, OS based on response to chemotherapy among metastatic patients, and OS and disease free survival (DFS) in surgically resected disease with vs. without adjuvant therapy. Data were analyzed using Kaplan-Meier and multivariate cox-regression analyses based on a 95% confidence interval (CI) or an α-value of 0.05. OS was significantly different based on the disease stage, with 3.63 (95% CI, 2.84-4.43), 6.57 (95% CI, 4.06-9.08) and 15.57 (95% CI, 11.79-19.35) months in the advanced, locally advanced, and localized disease groups, respectively. OS was higher in metastatic-stage patients who received chemotherapy [6.07 months (95% CI, 4.75-7.39)] compared with those who received supportive therapy alone [2.50 months (95% CI, 2.16-2.84; P<.001)]. Metastatic-stage patients with partial or stable response to chemotherapy had higher OS [10.53 months (95% CI, 6.35-14.72)] in comparison with those with progression [6.33 months (95% CI, 5.79-6.88)] or an undocumented response [3.30 months (95% CI, 1.76-4.84; P<0.001)]. In patients who underwent surgical resection of localized disease, adjuvant therapy increased the adjusted OS and DFS as compared with surgical excision alone (P=0.013; 95% CI, 0.278-0.862). Positive margins reduced OS [hazard ratio (HR) 2.670; 95% CI, 1.467-4.860]. The present single-site study has demonstrated that OS may markedly differ on the basis of the disease status at the time of diagnosis. Metastatic-stage patients with stable or partial response to chemotherapy had an increased OS, as did surgical patients with localized disease who received adjuvant treatment, after adjusting for margin status.