Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada.

There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.

A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy.

Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of single-agent regorafenib as a second-line therapy for mCRC patients who received it after failing first-line therapy with an oxaliplatin or irinotecan regimen with or without bevacizumab. Using various omics approaches, we also investigated putative biomarkers of response and resistance to regorafenib in metastatic lesions and blood samples in the same cohort. Overall, the safety profile of regorafenib seemed similar to the CORRECT trial, where regorafenib was administered as ≥ 2 lines of therapy. While the mutational landscape showed typical mutation rates for the top five driver genes (APC, KRAS, BRAF, PIK3CA, and TP53), KRAS mutations were enriched in intrinsically resistant lesions. Additional exploration of genomic-phenotype associations revealed several biomarker candidates linked to unfavorable prognoses in patients with mCRC using various approaches, including pathway analysis, cfDNA profiling, and copy number analysis. However, further research endeavors are necessary to validate the potential utility of these promising genes in understanding patients' responses to regorafenib treatment.

Fulminant Coxsackievirus Myocarditis in an Immunocompetent Adult: A Case Report and Literature Analysis.

Myocarditis is an inflammatory condition that impacts cardiac myocytes and is caused mostly by viruses. It can manifest as chest pain, dyspnea, palpitations, fatigue, syncope, shortness of breath, and in severe cases frank cardiogenic shock. It accounts for around 10 percent of all sudden cardiac deaths in young adults, who are described as being in their early thirties. Inflammatory cardiomyopathy resulting from acute myocarditis may also appear as new-onset heart failure (HF), delaying the diagnosis and treatment of these patients. It is crucial to recognize the sensitivity of symptom onset, especially in young individuals; mildly elevated troponin levels that are inconsistent with the severity of left ventricular ejection fraction (LVEF) impairment and associated left ventricular dilatation strongly suggest inflammatory cardiomyopathy rather than acute myocarditis. The current treatment for myocarditis is primarily supportive, with an emphasis on the management of heart failure and arrhythmias in accordance with clinical practice guidelines. In this case report, we describe a male in his early forties who presented with abrupt onset exertional shortness of breath and chest discomfort. His cardiac catheterization did not show evidence of coronary artery disease; however, an echocardiogram revealed new-onset heart failure with reduced ejection fraction, the diagnosis of coxsackievirus myocarditis was made based on his clinical presentation, and a positive coxsackievirus immunoassay.

Two-dimensional transthoracic echocardiographic demonstration of reduction in fibrin content in purulent pericarditis following intrapericardial fibrinolytic agent administration.

We describe an adult patient who presented with purulent pericarditis (PP) in whom two-dimensional transthoracic echocardiography demonstrated a marked decrease in the area of the right ventricular (RV) wall together with the overlying fibrin following intrapericardial administration of a fibrinolytic agent. Documentation of this decrease by measurements performed and illustrated on two-dimensional images has not been reported previously in an adult patient with PP, to the best of our knowledge.

Prostate Cancer Metastasis to the Pituitary Gland Manifesting as Corticosteroid Withdrawal, and the Impact of the Switch from Prednisone to Dexamethasone on Survival Time.

Despite improvements in the diagnosis and treatment of cancers, the incidence of pituitary metastasis has increased. Prostate cancer metastasis to the pituitary, however, is rare, and these tumors usually grow rapidly. They are also more likely to be located in the posterior pituitary, and the presenting symptoms are often nonspecific, which makes early diagnosis challenging. The management of this condition is usually multidisciplinary, and requires careful assessment and decision making. We present a case of a patient who developed prostate cancer metastasis to the pituitary. In this report, we show that patients with prostate cancer on corticosteroid therapy who develop withdrawal symptoms or other endocrine symptoms should be assessed for pituitary and other brain metastasis. This case report also discusses the impact of switching from prednisone and abiraterone to dexamethasone and abiraterone. Our report shows that patients on abiraterone and prednisone whose PSA has increased, but who have no radiologic progression, may have their PSA controlled and thereby improved survival time when they are switched to abiraterone and dexamethasone.

Global effect of COVID-19 pandemic on the rate of acute coronary syndrome admissions: a comprehensive review of published literature.

BACKGROUND: The COVID-19 pandemic has disrupted healthcare systems across the world. The rate of acute coronary syndrome (ACS) admissions during the pandemic has varied significantly. OBJECTIVES: The purpose of this study is to investigate the effect of the pandemic on ACS hospital admissions and to determine whether this is related to the number of COVID-19 cases in each country. METHOD: Search engines including PubMed, Embase, Ovid and Google Scholar were searched from December 2019 to the 15 September 2020 to identify studies reporting ACS admission data during COVID-19 pandemic months in 2020 compared with 2019 admissions. RESULTS: A total of 40 studies were included in this multistudy analysis. They demonstrated a 28.1% reduction in the rate of admission with ACS during the COVID-19 pandemic period compared with the same period in 2019 (total of 28 613 patients in 2020 vs 39 225 in 2019). There was a significant correlation between the absolute risk reduction in the total number of ACS cases and the number of COVID-19 cases per 100 000 population (Pearson correlation=0.361 (p=0.028)). However, the correlation was not significant for each of the ACS subgroups: non-ST-elevation myocardial infarction (STEMI) (p=0.508), STEMI (p=0883) and unstable angina (p=0.175). CONCLUSION: There was a significant reduction in the rate of ACS admission during the COVID-19 pandemic period compared with the same period in 2019 with a significant correlation with COVID-19 prevalence.

Short- and Long-Term Outcomes in Patients With New-Onset Persistent Left Bundle Branch Block After Transcatheter Aortic Valve Replacement.

BACKGROUND: The impact of new-onset persistent left bundle branch block (LBBB) after transcatheter aortic valve replacement (TAVR) on all-cause mortality has been controversial. METHODS: We conducted a systematic review and meta-analysis of eleven studies (7398 patients) comparing the short- and long- outcomes in patients who had new-onset LBBB after TAVR vs. those who did not. RESULTS: During a mean follow-up of 20.5±14months, patients who had new-onset persistent LBBB after TAVR had a higher incidence of all-cause mortality (29.7% vs. 23.6%; OR 1.28 (1.04-1.58), p=0.02), rehospitalization for heart failure (HF) (19.5% vs. 17.3%; OR 1.4 (1.13-1.73), p=0.002), and permanent pacemaker implantation (PPMi) (19.7% vs. 7.1%; OR 2.4 (1.64-3.52), p<0.001) compared with those who did not. Five studies (4180 patients) reported adjusted hazard ratios (HR) for all-cause mortality; new LBBB remained associated with a higher risk of mortality (adjusted HR 1.43 (1.08-1.9), p<0.01, I2=81%). CONCLUSION: Post-TAVR persistent LBBB is associated with higher PPMi, HF hospitalizations, and all-cause mortality. While efforts to identify patients who need post-procedural PPMi are warranted, more studies are required to evaluate the best follow-up and treatment strategies, including the type of pacing device if required, to improve long-term outcomes in these patients.

Cardiac Magnetic Resonance Imaging Features in Hypertrophic Cardiomyopathy Diagnosed at <21 Years of Age.

Hypertrophic cardiomyopathy (HC) is the most common inherited cardiomyopathy, with varied timing of phenotypic and clinical presentation. Literature describing cardiac magnetic resonance (CMR) imaging and late gadolinium enhancement (LGE) in young patients with HC is limited. This study included patients diagnosed with HC at young age (<21 years) between January 1990 and January 2015 who underwent transthoracic echocardiography and CMR with assessment of LGE at a single tertiary referral center. LGE was quantified via a method of 6 standard deviations and patients were grouped based upon presence or absence of LGE (≤1% and >1% LGE, respectively). Sudden cardiac death (SCD) risk was assessed in patients >16 years of age using the European SCD risk score. A composite outcome of New York Heart Association class III-IV symptoms, aborted SCD, heart transplantation, and all-cause mortality was assessed via Kaplan-Meier curves with log-rank analysis. Overall, 126 patients were included (78 male; 62%). Median age of diagnosis was 15 (12 to 18) years. LGE was present in 81 (64%) patients, although only 4 (3%) patients had LGE >15%. Median age at CMR imaging was 19 (15 to 23) years. Patients with LGE had greater wall thickness (25 ± 8 mm vs 22 ± 7 mm, p = 0.01). Median European SCD risk score was 4.7 (2.9 to 6.5). Median follow-up was 6.5 (2.5 to 13) years with 26 patients (21%) meeting the composite outcome. There were no significant differences in composite outcome since age of diagnosis when stratified by presence/absence of LGE (p = 1.0). The presence of LGE in young HC patients was not an independent risk factor for cardiovascular morbidity and mortality. Wall thickness was greater in patients with LGE. There remains a need for further evaluation of this unique HC cohort.

Usefulness of right ventricular strain assessment in submassive pulmonary thromboembolism undergoing ultrasound-facilitated thrombolysis.

Massive and submassive pulmonary thromboembolism carry significant morbidity and mortality. We present an elderly female who was diagnosed with a submassive pulmonary embolism by computed tomographic angiography and treated with ultrasound-facilitated thrombolysis (UFT). This case demonstrates the usefulness of right ventricular longitudinal strain measurements by two-dimensional speckle tracking echocardiography in the evaluation of right ventricular function before and after UFT. Evaluation of right ventricle longitudinal strain by speckle tracking echocardiography may supplement other parameters in the assessment of right ventricular function in these patients.

Incremental value of right parasternal transthoracic echocardiographic examination over the left parasternal approach in assessing ascending aorta size: Additional benefit of three-dimensional echocardiography.

BACKGROUND: The ascending aorta (AA) has not been well studied using two-dimensional right parasternal transthoracic echocardiographic examination (2DRPE). AIM: The aim of the present study was to assess the incremental value of 2DRPE over two-dimensional left parasternal transthoracic echocardiographic examination (2DLPE) in evaluating the size of AA in adult patients (pts) and, secondly, to determine whether live/real time three-dimensional (3D) RPE provided any additional benefit over 2DRPE. MATERIALS AND METHODS: The AA was successfully imaged by 2DLPE, 2DRPE, and 3D RPE in 87 of 141 (61.7%) pts which comprised of two groups of consecutive pts separated by an interval of 2 weeks. RESULTS: The maximum length of AA visualized by 2DRPE (4.98 ± 0.89) was larger than 2DLPE in 76/87(87%) pts (P < 0.001). Both the maximum systolic AA inner luminal width and leading edge-to-leading edge width by 2DRPE were greater than 2DLPE (P < 0.001). Similar to other noninvasive imaging modalities where mid-AA width is taken at level of right pulmonary artery, mid-AA width could also be taken at this level by 2DRPE in 79/87(91%) pts since this landmark was visualized during 2DRPE. However, this vessel could be visualized in only 2/87 (2%) pts with 2DLPE. 3DRPE conferred additional benefit over 2DRPE. The maximal AA length by 3DRPE was larger than 2DRPE in 60/87(69%) pts, and the maximal inner lumen and leading edge to leading edge widths were larger in 54/87(62%) and 66/87(76%) pts, respectively. CONCLUSION: Our preliminary study demonstrates significant incremental value of 2DRPE over 2DLPE in the assessment of AA. 3DRPE confers an additional advantage over 2DRPE.

Comparison of Laser In Situ Keratomileusis Flap Morphology and Predictability by WaveLight FS200 Femtosecond Laser and Moria Microkeratome: An Anterior Segment Optical Coherence Tomography Study.

PURPOSE: To evaluate laser in situ keratomileusis (LASIK) flap thickness predictability and morphology by femtosecond (FS) laser and microkeratome (MK) using anterior segment optical coherence tomography. METHODS: Fifty-two candidates for the LASIK procedure were stratified into two groups: FS laser-assisted (Allegretto FS-200) and MK flap creation (Moria 2). Flap thickness was determined at five points. The side-cut angle was measured in three directions at the margin interface. LASIK flap assessment was performed one month postoperatively by Spectralis anterior segment optical coherence tomography. RESULTS: Fifty-two patients (93 eyes) were recruited; 49 eyes were stratified to the FS group and 44 eyes to the MK group. The FS group had relatively even flap configurations, and the MK group had meniscus-shaped flaps. Mean differences between planned and actual flap thickness were 12.93 ± 8.89 and 19.91 ± 5.77 µm in the FS and MK groups, respectively. In thin flaps (100 to 110 µm), there was a significant disparity between the two groups (7.80 ± 4.71 and 19.44 ± 4.46 µm in the FS and MK groups, respectively). However, in thicker flaps (130 µm), comparable flap thickness disparity was achieved (18.54 ± 9.52 and 20.83 ± 5.99 µm in the FS and MK groups, respectively). Mean side-cut angle was 74.29 ± 5.79 degrees and 32.34 ± 4.94 degrees in the FS and MK groups, respectively. CONCLUSIONS: Comparable flap thickness predictability was achieved in thicker flaps (130 µm), while the FS laser technique yielded a more predictable result in thinner flaps (100 to 110 µm). Different flap morphology was observed in meniscus flaps in MK-LASIK and flap morphology in FS-LASIK.

Prognostic value of segment involvement score compared to other measures of coronary atherosclerosis by computed tomography: A systematic review and meta-analysis.

BACKGROUND: The segment involvement score (SIS) is a semiquantitative measure of the extent of atherosclerosis burden by coronary computed tomography angiography (CTA). We sought to evaluate by meta-analysis the prognostic value of SIS, and to compare it with other CTA measures of coronary artery disease (CAD). METHODS: Electronic databases from 1946 to January 2016 were searched. Studies reporting SIS, or an equivalent measure by coronary CTA, and clinical outcomes were included. Maximally adjusted hazard ratios (HR), predominantly for clinical variables, were extracted for SIS, obstructive CAD, Agatston coronary artery calcium score, and plaque composition. These were pooled using DerSimonian-Laird random effects models. RESULTS: Eleven nonrandomized studies with good methodological quality enrolling 9777 subjects (mean age 61 ± 11 years, 57% male, mean follow up 3.3 years) who had 472 (4.8%) MACE (cardiac or all cause death, non-fatal myocardial infarction or late revascularization), were included. SIS (per segment increase) had pooled HR of 1.25 (95% CI: 1.16,1.35; I2 = 71.4%, p < 0.001) for MACE. HR for MACE was 1.37 (95% CI: 1.32,1.42; I2 = 95.6%, p < 0.001) for number of segments with stenosis (per segment increase), 3.39 (95% CI: 1.65,6.99; I2 = 87.8%, p = 0.001) for obstructive CAD (binary variable) and 1.00 (95% CI: 1.00,1.01; I2 = 75.0%, p = 0.490) for Agatston score (per unit increase). HRs by plaque composition (calcified, non-calcified and mixed; per segment change) were 1.24 (95% CI: 1.10,1.39; I2 = 81.6%, p = 0.001), 1.20 (95% CI: 0.97,1.48; I2 = 92.9%, p = 0.093) and 1.27 (95% CI: 1.03,1.58; I2 = 89.8%, p = 0.029), respectively. CONCLUSION: Despite heterogeneity in endpoints, extent of CAD as quantified by SIS on coronary CTA is a strong, independent predictor of cardiovascular events.

77-year-old female with syncope.

CLINICAL INTRODUCTION: A 77-year-old female was referred for evaluation of an episode of syncope while eating breakfast. There was no history of fall, syncope, prodrome, dyspnoea, chest discomfort or palpitations. Medical history was notable for hyperlipidaemia and treated hypertension. Blood pressure was 140/90 mm Hg, pulse 85  beats per minute (BPM). No murmurs were present on cardiac examination. ECG revealed normal sinus rhythm with left ventricular (LV) hypertrophy (see online supplementary figure S1). Holter monitor demonstrated rare premature ventricular complexes (<1% of beats), without heart block or ventricular tachycardia. Transthoracic echocardiogram is shown in figure 1. QUESTION: Which of the following is the explanation for the flow indicated by the yellow arrow? Aortic stenosisCoronary artery flow, indicative of coronary fistulaHypertrophic cardiomyopathy with apical pouchHypertensive heart diseaseMitral stenosis.

A simple prognostic model for overall survival in metastatic renal cell carcinoma.

INTRODUCTION: The primary purpose of this study was to develop a simpler prognostic model to predict overall survival for patients treated for metastatic renal cell carcinoma (mRCC) by examining variables shown in the literature to be associated with survival. METHODS: We conducted a retrospective analysis of patients treated for mRCC at two Canadian centres. All patients who started first-line treatment were included in the analysis. A multivariate Cox proportional hazards regression model was constructed using a stepwise procedure. Patients were assigned to risk groups depending on how many of the three risk factors from the final multivariate model they had. RESULTS: There were three risk factors in the final multivariate model: hemoglobin, prior nephrectomy, and time from diagnosis to treatment. Patients in the high-risk group (two or three risk factors) had a median survival of 5.9 months, while those in the intermediate-risk group (one risk factor) had a median survival of 16.2 months, and those in the low-risk group (no risk factors) had a median survival of 50.6 months. CONCLUSIONS: In multivariate analysis, shorter survival times were associated with hemoglobin below the lower limit of normal, absence of prior nephrectomy, and initiation of treatment within one year of diagnosis.

Acromegaly-induced cardiomyopathy with dobutamine-induced outflow tract obstruction.

A 50-year-old man with a history of acromegaly was referred for preoperative cardiac evaluation preceding trans-sphenoidal resection of a pituitary macroadenoma. Dobutamine stress echocardiography was negative for myocardial ischaemia. Resting left ventricular (LV) LV ejection fraction (LVEF) was 64% and there was hypertrophy of ventricular septum (18 mm) without resting LV outflow tract obstruction. With 40 µg/kg/min of dobutamine, the LVEF became hyperdynamic at 80%, and there was a maximal instantaneous LV outflow tract gradient of 77 mm Hg. There was no delayed myocardial enhancement on cardiac MRI and the pattern of hypertrophy was concentric. Acromegaly-induced cardiomyopathy can mimic hypertrophic cardiomyopathy in the setting of dobutamine provocation. Because cardiomyopathy is an important cause of mortality in acromegaly, diagnosis and appropriate management are critical to improve survival.

Attitudes of physicians toward assessing risk and using granulocyte colony-stimulating factor as primary prophylaxis in patients receiving chemotherapy associated with an intermediate risk of febrile neutropenia.

Febrile neutropenia (FN) is a potentially fatal complication of chemotherapy. This prospective, observational study describes physicians' approaches toward assessing FN risk in patients receiving chemotherapy regimens with an intermediate (10-20 %) FN risk. In the baseline investigator assessment, physicians selected factors considered important when assessing overall FN risk and deciding on granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (PP). Physicians then completed patient assessments using the same lists of factors. The final FN risk scores and whether G-CSF PP was planned were reported. The final analysis included 165 physicians and 944 patients. The most frequently considered factor in both assessments was chemotherapy agents in the backbone (88 % of investigator and 93 % of patient assessments). History of FN (83 %), baseline laboratory values (76 %) and age (73 %) were commonly selected at baseline, whereas tumor type (72 %), guidelines (62 %) and tumor stage (43 %) were selected most during patient assessments. Median investigator-reported FN risk threshold for G-CSF PP was 20 % (range 10-85 %). G-CSF PP was planned in 82 % of patients with an FN risk at or above this threshold; therefore, almost one-fifth of qualifying patients would not receive G-CSF PP. Physicians generally follow guidelines, but also consider individual patient characteristics when assessing FN risk and deciding on G-CSF PP. A standardized FN risk assessment may optimize the use of G-CSF PP, which may minimize the incidence of FN in patients undergoing chemotherapy with an intermediate FN risk. ClinicalTrials.gov Identifier: NCT01813721.

Controversial indications for sentinel lymph node biopsy in breast cancer patients.

Sentinel lymph node biopsy (SLNB) emerged in the 1990s as a new technique in the surgical management of the axilla for patients with early breast cancer, resulting in lower complication rates and better quality of life than axillary lymph node dissection (ALND). Today SLNB is firmly established in the armamentarium of clinicians treating breast cancer, but several questions remain. The goal of this paper is to review recent work addressing 4 questions that have been the subject of debate in the use of SLNB in the past few years: (a) What is the implication of finding micrometastases in the sentinel nodes? (b) Is ALND necessary in all patients who have a positive SLNB? (c) How accurate is SLNB after neoadjuvant therapy? (d) Can SLNB be used to stage the axilla in locally recurrent breast cancer following breast surgery with or without prior axillary surgery?

Clinico-pathological study of K-ras mutations in colorectal tumors in Saudi Arabia.

AIMS AND BACKGROUND: K-ras gene mutations contribute to the pathogenesis of colorectal cancer. We characterized K-ras mutations in colorectal tumors in patients in the Kingdom of Saudi Arabia, in terms of geographic area, age, gender, histology, stage, and anatomical localization. METHODS: Medical records and paraffin-embedded tumor samples from 150 consecutive patients with histologically proven colorectal adenocarcinoma referred to two centers in Saudi Arabia were analyzed using an LCD-array kit. RESULTS: K-ras mutations occurred in 56% of the patients; 48.7% of the mutations were in codon 12, most commonly p.G12V and p.G12D (each 35.6% of codon 12 mutations). Codon 13 mutations occurred in 7.3% of tumors: of these, most were p.G13D (90.9%) with the remainder p.G13R (9.1%). Codon 12 mutations overall were associated significantly with stage IVb tumors (P = 0.022) and rectal tumors (P = 0.028), with a trend of an association with a sigmoid location (P = 0.054). The p.G12V mutation was significantly associated with sigmoid tumors (P = 0.021) and negatively associated with left-sided tumors (P = 0.011), with a trend of an association with age ≥70 years (P = 0.062) and rectal tumors (P = 0.063). Other clinicopathological features were not significantly associated with K-ras mutations. CONCLUSIONS: K-ras mutations are common among the Saudi colorectal cancer population, especially pG12V and pG12D in codon 12, and are more frequent in sigmoid and rectal adenocarcinomas and stage IVB tumors.