Curr. Oncol., Volume 29, Issue 3 (March 2022) – 66 articles

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area (the province of Belluno). The clinicopathological profile of CMM by residence is also considered. A joinpoint regression analysis was performed to identify significant changes in the yearly incidence of CMM by sex and age. For each trend, the average annual percent change (AAPC) was also calculated. In the 2017 CMM cohort, the study includes a descriptive analysis of the disease’s categorical clinicopathological variables. In the population investigated, the incidence of CMM has increased significantly over the last 30 years. The AAPC in the incidence of CMM was significantly higher among Alpine residents aged 0–49 than for the rest of the region’s population (males: 6.9 versus 2.4; females 7.7 versus 2.7, respectively). Among the Alpine residents, the AAPC was 3.35 times greater for females aged 0–49 than for people aged 50+. The clinicopathological profile of CMM was significantly associated with the place of residence. Over three decades, the Veneto population has observed a significant increase in the incidence of CMM, and its AAPC. Both trends have been markedly more pronounced among Alpine residents, particularly younger females. While epidemiology and clinicopathological profiles support the role of UV radiation in CMM, the young age of this CMM-affected female population points to other possible host-related etiological factors. These findings also confirm the importance of primary and secondary prevention strategies. Full article

Plasma-based next-generation sequencing (NGS) has demonstrated the potential to guide the personalized treatment of non-small cell lung cancer (NSCLC). Inherent differences in mutational genomic profiles of NSCLC exist between Asian and Western populations. However, the published mutational genomic data of NSCLC has largely focused on Western populations. We retrospectively analyzed results from comprehensive NGS of plasma (Guardant360^®) from patients with advanced non-squamous NSCLC, as seen in clinical practice. Tests were ordered between January 2016 and December 2020 in Hong Kong, Korea, Taiwan, Japan and Southeast Asia. The assay identified single-nucleotide variants (SNV), insertions and deletions, and fusions and amplifications in 74 genes. In total, 1608 plasma samples from patients with advanced non-squamous NSCLC were tested. The median turnaround time for test results was 7 days. Of the samples with detectable ctDNA (85.6%), 68.3% had alterations in at least one NCCN-recommended NSCLC biomarker. EGFR driver mutations were most frequent (48.6%), followed by alterations of KRAS (7.9%), ERBB2 (4.1%) and ALK (2.5%). Co-mutations of EGFR and KRAS occurred in 4.7% of samples. KRAS G12C was identified in 18.6% of all samples with KRAS mutations. Common mutations, such as exon 19 deletions and L858R, accounted for 88.4% of EGFR driver mutations. Among the samples with any EGFR driver mutation, T790M was present in 36.9%, including 7.7% with additional alterations associated with osimertinib resistance (MET amplification, C797X). Comprehensive plasma-based NGS provided the timely and clinically informative mutational genomic profiling of advanced non-squamous NSCLC in East Asian patients. Full article

Anxiety and depression are frequent among patients with breast cancer (BCa). Evidence of the persistence and recovery from these conditions and their determinants is scarce. We describe the occurrence of clinically significant anxiety and depression symptoms and their associated factors among BCa patients. A total of 506 women admitted in 2012 at the Portuguese Institute of Oncology of Porto were evaluated before treatment and after one, three, and five years (7.9% attrition rate). The five-year prevalence of anxiety and/or depression (Hospital Anxiety and Depression Scale, subscores ≥ 11) was 55.4%. The peak prevalence for anxiety was before treatment (38.0%), and after one year for depression (13.1%). One in five patients with anxiety/depression at baseline had persistent anxiety/depression over time, while only 11% and 22% recovered permanently from anxiety and depression, respectively, during the first year. Higher education, higher income, practicing physical activity, and adequate fruit and vegetable intake were protective factors against anxiety and/or depression. Loss of job and income, anxiolytics and antidepressants, cancer-related neuropathic pain, and mastectomy were associated with higher odds of anxiety and/or depression. These results highlight the importance of monitoring anxiety/depression during the first five years after cancer diagnosis and identify factors associated with these conditions. Full article

Ovarian cancer (OC) is the leading cause of death among women with gynecologic malignancy. Breast Cancer Susceptibility Gene 1 (BRCA 1) and Breast Cancer Susceptibility Gene 2 (BRCA 2) germline mutations confer an estimated 20 to 40 times increased risk of OC when compared to the general population. The majority of BRCA-associated OC is identified in the late stage, and no effective screening method has been proven to reduce mortality. Several pharmacologic and surgical options exist for risk-reduction of gynecologic malignancy in BRCA 1/2 mutation carriers. This review summarizes up-to-date research on pharmacologic risk-reducing interventions, including the oral contraceptive pill, acetylsalicylic acid/nonsteroidal anti inflammatory drugs (ASA/NSAID) therapy, and denosumab, and surgical risk-reducing interventions, including risk-reducing bilateral salpingo-oophorectomy, salpingectomy with delayed oophorectomy, and hysterectomy at the time of risk-reducing bilateral salpingo-oophorectomy. Full article

For women with genetic risk of breast cancer, the addition of screening breast MRI to mammography has become a standard. The order and interval of annual imaging can be variable among providers. To evaluate the clinical implications related to the timing, we conducted a chart review on a cohort of women (N = 276) with high-risk (BRCA1, BRCA2, CDH1, PTEN and TP53) and moderate high-risk (ATM and CHEK2) predisposition to breast cancer in a 48-month follow up. The estimated MRI detection rate in the entire group is 1.75% (18 per 1000 MRI tests). For the high-risk group, the estimated rate is 2.98% (30 per 1000 MRI tests). Many women discovered their genetic risk at an age much older (average age of the high-risk group was 48 years) than the age recommended to initiate enhanced screening (age 20 to 25 years). In total, 4 of the 11 primary breast cancers detected were identified by screening MRI within the first month after initial visit, which were not detected by previous mammography, suggesting the benefit of initiating MRI immediately after the discovery of genetic risk. Breast screening findings for women with Lynch syndrome and neurofibromatosis type 1 were also included in this report. Full article

Our objective was to examine the prevalence of mental health symptoms and the behavioral impact of the COVID-19 pandemic on cancer survivors who endorse cannabis. Participants included 158 adults (≥18 years) who self-reported medicinal cannabis use and responded to our internet-based questionnaire (21 March 2020–24 March 2021). Data included 79 cancer survivors and 79 age-matched adults without a history of cancer. Descriptive statistics were used to compare demographics, the prevalence of generalized anxiety (GAD-7), depression (CES-D-10), and changes in behavior during the COVID-19 pandemic by cancer survivorship status. Overall, 60.8% and 48.1% of cancer survivors self-reported the use of cannabis to manage their anxiety and depression, respectively. Probable clinical depression (CES-D-10 score ≥ 10) and anxiety (GAD-7 score ≥ 10) were identified in 50.7% and 38.9% of cancer survivors, respectively. Cancer survivors were more likely to report that their anxiety symptoms made it very or extremely difficult to work, take care of home, or get along with others than their counterparts. Cancer survivors with anxiety and/or depression were more likely to fear giving COVID-19 to someone else (47.5% vs. 23.1%, p = 0.023) and to fear being diagnosed with COVID-19 (77.5% vs. 38.5%, p < 0.001) compared to cancer survivors without anxiety and depression symptoms. Further research is recommended to evaluate the use of cannabis as palliative care to improve mental health among cancer survivors. Full article

The incidence of BM among Canadian cancer patients is unknown. We aimed to estimate IP of BM at the time of cancer diagnosis and during the lifetime of patients with selected primary cancers. Data on BM at diagnosis from 2010–2017 was obtained from the CCR. Site-specific IPs of BM were estimated from provincial registries containing ≥90% complete data on BM. The CCR IP estimates and the IP estimates from literature were applied to the total diagnosed primary cancers to estimate the number of concurrent BM and lifetime BM from 2010–2017 in Canada, respectively. The annual average number of patients with BM at diagnosis from all cancer sites was approximately 3227. The site-specific IPs of BM at diagnosis were: lung (9.42%; 95% CI: 9.16–9.68%), esophageal (1.58%; 95% CI: 1.15–2.02%), kidney/renal pelvis (1.33%; 95% CI: 1.12–1.54%), skin melanoma (0.73%; 95% CI: 0.61–0.84%), colorectal (0.22%; 95% CI: 0.18–0.26%), and breast (0.21%; 95% CI: 0.17–0.24%). Approximately 76,546 lifetime BM cases (or 5.70% of selected fifteen primary cancers sites) were estimated to have occurred from the 2010–2017 cancer patient cohort. These findings reflect results of population analyses in the US and Denmark. We recommend improved standardization of the collection of BM data within the CCR. Full article

Aims: In 2014, in response to evidence that Canada’s tobacco use would lead, inexorably, to substantial morbidity and mortality for the foreseeable future, a group of experts convened to consider the development of a “Tobacco Endgame” for Canada. The “Tobacco Endgame” defines a time frame in which to eliminate structural, political, and social dynamics that sustain tobacco use, leading to improved population health. Strategies: A series of Background Papers describing possible measures that could contribute to the creation of a comprehensive endgame strategy for Canada was prepared in advance of the National Tobacco Endgame Summit hosted at Queen’s University in 2016. At the summit, agreement was reached to work together to achieve <5% tobacco use by 2035 (<5 by ’35). A report of the proceedings was shared widely. Achievements: Progress since 2016 has been mixed. The Summit report was followed by a national forum convened by Health Canada in March 2017, and in 2018, the Canadian Government adopted “<5 × ’35” tobacco use target in a renewed Canadian tobacco reduction strategy. Tobacco use has declined in the last 5 years, but at a rate slower than that which will be needed to achieve the <5 by ’35 goal. There remain > 5 million smokers in Canada, signaling that smoking-related diseases will continue to be an enormous health burden. Furthermore, the landscape of new products (e-cigarettes and cannabis) has created additional risks and opportunities. Future directions: A bold, reinvigorated tobacco control strategy is needed that significantly advances ongoing policy developments, including full implementation of the key demand-reduction policies of the WHO Framework Convention on Tobacco Control. Formidable, new disruptive policies and regulations will be needed to achieve Canada’s Endgame goal. Full article

We assessed whether advanced RT techniques were associated with differences in patient-reported outcomes (PROs). Patients with bone metastases who completed the brief pain inventory (BPI) before and after RT were identified, and RT technique was categorized as simple (e.g., parallel opposed pair) or advanced (e.g., 3D-conformal RT (3DCRT), intensity-modulated RT (IMRT), or stereotactic ablative RT (SABR)). Pain response and patient-reported interference on quality of life secondary to pain was compared. A total of 1712 patients completed the BPI. From 2017–2021, the rate of advanced RT technique increased significantly (p < 0.001; 2.4%, 2.4%, 9.7%, 5.5%, 9.3%), with most advanced techniques consisting of IMRT, and only 7% of advanced techniques were SABR. Comparing simple vs. advanced technique, neither the complete pain response (12.3% vs. 11.4%; p = 0.99) nor the partial pain response (50.0% vs. 51.8%; p = 0.42) was significantly different. There was no significant patient-reported difference in pain interfering with general activity, mood, walking ability, normal work, relationships, sleep, or enjoyment of life. Given that there is increasing utilization of advanced RT techniques, there is further need for randomized trials to assess their benefits given the increased cost and inconvenience to patients. Full article

Canada lacks a national drug insurance plan. The home province or territory of a patient determines which cancer drugs are available on the public formulary, who is eligible for public coverage and what portion of the financial burden of cancer care falls to the individual. This narrative review describes the current interprovincial disparities in access to cancer drugs across Canada. Health technology assessment (HTA) of drugs at a provincial and territory level is a closed process, does not necessarily follow the recommendations of national HTA and leads to further delays in drug access. The public coverage of take-home cancer drugs (THCDs) in Ontario and the Atlantic provinces is often fragmented, unnecessarily complex and a barrier to cancer drug access. Policy solutions to address inter-provincial formulary variation and poor access to THCDs are discussed. Full article

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada. Full article

For patients with Mantle Cell Lymphoma (MCL), there is no recognized standard of care for relapsed/refractory (R/R) disease after treatment with a Bruton’s tyrosine kinase inhibitor (BTKi). Brexucabtagene autoleucel (brexu-cel) represents a promising new treatment modality in MCL. We explored whether brexu-cel was cost-effective for the treatment of R/R MCL. We developed a partitioned survival mixture cure approach to model the costs and outcomes over a lifetime horizon. The clinical data were derived from the ZUMA-2 clinical trial. The costs were estimated from the publicly available Canadian databases, published oncology literature, and pan-Canadian Oncology Drug Review economic guidance reports. The health state utilities were sourced from the ibrutinib submission to the National Institute for Health and Care Excellence for R/R MCL and supplemented with values from the published oncology literature. In the base case over a lifetime horizon, brexu-cel generated an incremental 9.56 life-years and an additional 7.03 quality-adjusted life-years compared to BSC, while associated with CAD 621,933 in additional costs. The resultant incremental cost-utility ratio was CAD 88,503 per QALY gained compared with BSC. Based on this analysis, we found brexu-cel to be a cost-effective use of healthcare resources relative to BSC for treatment of adult patients with R/R MCL previously treated with a BTKi in Canada, though additional research is needed to confirm these results using longer follow-up data. Full article

The management of patients with hormone receptor-positive breast cancer has changed dramatically with use of the 21-gene Recurrence Score^® (RS) Assay. While the utility of the assay was initially demonstrated among node-negative patients, recent studies have also demonstrated the assay’s prognostic and predictive value in node-positive patients. In Canada, the RS assay is reimbursed by provincial health insurance plans, but not all provinces have approved the use of the assay for patients with node-positive disease. Here, we provide an overview of the clinical factors that influence physician recommendation of the RS assay and, alternatively, the impact of the RS assay on patient treatment decisions in Canada. We performed a comprehensive review of the impact of the assay upon physician treatment decisions and cost in node-positive breast cancer patients within Canada and other countries. Furthermore, we evaluated biomarkers that can predict the RS result, in addition to other genomic assays that predict recurrence risk among node-positive patients. Overall, the 21-gene RS assay was shown to be a cost-effective tool that significantly reduced the use of chemotherapy in node-positive breast cancer patients in Canada. Full article

Background: Canada has a publicly funded healthcare system with a complex drug funding process. After Health Canada approval to market a drug, the pan-Canadian Oncology Drug Review (pCODR) (now renamed the CADTH reimbursement review) makes a non-binding funding recommendation to the Canadian provinces (except Quebec), which each then decide whether the drug will be publicly funded. We identified the determinants of funding in this process. Methods: We analyzed drugs for advanced lung (n = 15), breast (n = 8), colorectal (CRC) (n = 7), melanoma (n = 10), and neuroendocrine (NET) (n = 3) cancers undergoing the funding decision process from 2011 to 2019. Determinants of funding assessed in the model included list price, cancer type, drug class, and pCODR recommendation. The primary outcome was the correlation between list price and time to funding (TTF: Health Canada approval to first provincial funding). Secondary outcomes included an exploratory analysis of predictors of drug funding. Results: We analyzed 43 drugs: targeted agents 72%, immunotherapy 20%, chemotherapy 7%. A total of 72% were funded in at least one province. Median TTF was 379 days (IQR 203–601). Median list price (28-day course) was CAD 8213 (IQR CAD 5391–9445). Higher list price was not correlated with TTF (correlation coefficient −0.20, p = 0.28). There was no association between list price and pCODR recommendation or the decision to fund in at least one province. A positive pCODR recommendation correlated with the provinces’ funding decisions (p < 0.001), where 89% of drugs with a positive recommendation were funded and 100% of drugs with a negative recommendation were not funded. Tumor type was predictive of TTF (p < 0.001): CRC drugs were the slowest at a median of 2541 days (IQR 702–4379), and NETs were the quickest at a median of 0 days (IQR 0–502). Cancer type predicted decision to fund in at least one province (p = 0.005), with funding for 100% of NET drugs at the high end and 29% of CRC drugs at the low end. Drug class was predictive of TTF (p = 0.01): 465 days (IQR 245–702) for targeted agents, 443 days (IQR 298–587) for chemotherapy, and 339 days (IQR 164–446) for immunotherapy. Conclusions: Determinants of drug funding included cancer type, drug class, and pCODR recommendation but not list price. Factors other than cost were more heavily weighted in the funding decisions of cancer drugs in Canadian provinces. Full article

Perioperative chemotherapy is the standard of care for patients undergoing curative resection for gastroesophageal adenocarcinoma. However, less than 50% of patients complete postoperative chemotherapy, and the added benefit to preoperative chemotherapy remains unclear. The aim of this study was to compare disease-free and overall survival (DFS and OS) in patients with perioperative chemotherapy to those who received preoperative chemotherapy only. In addition, a current literature overview is included. This multicenter, retrospective case series included 124 patients with gastroesophageal adenocarcinoma undergoing potentially curative resection and receiving pre- or perioperative chemotherapy between 2006 and 2010. Histopathological, demographic, clinical, and survival data were used to identify the impact of perioperative vs. preoperative chemotherapy on DFS and OS. Patients with perioperative chemotherapy had significantly improved DFS and OS (median DFS 28.0 months; 95%CI 0–62.4 vs. 19.0 months; 95%CI 10.5–27.5; p = 0.008 and median OS 35.7 months; 95%CI 0–73.6 vs. 19.2 months; 95%CI 7.8–30.4; p = 0.002). However, in contrast to patients with tumor-free lymph nodes at the time of resection, patients with positive lymph node status did not significantly benefit from additional postoperative chemotherapy in subgroup analysis. Further studies are encouraged to investigate optimal adjuvant treatment strategies for primary chemotherapy-resistant patients. Full article

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014–2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population. Full article

Purpose:The purpose of this study was to discriminate between benign and malignant breast lesions through several classifiers using, as predictors, radiomic metrics extracted from CEM and DCE-MRI images. In order to optimize the analysis, balancing and feature selection procedures were performed. Methods: Fifty-four patients with 79 histo-pathologically proven breast lesions (48 malignant lesions and 31 benign lesions) underwent both CEM and DCE-MRI. The lesions were retrospectively analyzed with radiomic and artificial intelligence approaches. Forty-eight textural metrics were extracted, and univariate and multivariate analyses were performed: non-parametric statistical test, receiver operating characteristic (ROC) and machine learning classifiers. Results: Considering the single metrics extracted from CEM, the best predictors were KURTOSIS (area under ROC curve (AUC) = 0.71) and SKEWNESS (AUC = 0.71) calculated on late MLO view. Considering the features calculated from DCE-MRI, the best predictors were RANGE (AUC = 0.72), ENERGY (AUC = 0.72), ENTROPY (AUC = 0.70) and GLN (gray-level nonuniformity) of the gray-level run-length matrix (AUC = 0.72). Considering the analysis with classifiers and an unbalanced dataset, no significant results were obtained. After the balancing and feature selection procedures, higher values of accuracy, specificity and AUC were reached. The best performance was obtained considering 18 robust features among all metrics derived from CEM and DCE-MRI, using a linear discriminant analysis (accuracy of 0.84 and AUC = 0.88). Conclusions: Classifiers, adjusted with adaptive synthetic sampling and feature selection, allowed for increased diagnostic performance of CEM and DCE-MRI in the differentiation between benign and malignant lesions. Full article

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have limited treatment options, particularly if they are transplantation or chimeric antigen receptor (CAR) T-cell ineligible, and novel therapeutics are needed. An 86-year-old woman with relapsed DLBCL received a novel, first-in-class small molecule inhibitor of N-myristoyltransferase (NMT) as the initial patient on a phase I dose escalation trial. Daily oral administration of 20 mg PCLX-001 tablets produced a pharmacokinetic profile suitable for single daily dosing: rapid oral absorption, followed by an apparent elimination half-life of 16 h, without systemic accumulation of drug by day 15. Pharmacodynamic tests showed no clear change in NMT1 and NMT2 levels or selected NMT substrate Lyn and HGAL protein levels in normal circulating blood mononuclear cells, suggesting a higher dose will be required for normal tissue toxicity. The patient did not experience any dose-limiting toxicities but had disease progression after 28 days of study therapy. Dose escalation continues in other patients in this first-in-human study of a new class of anticancer drug. We conclude that PCLX-001 oral monotherapy has suitable pharmacokinetic parameters for dose escalation, and that higher doses are required to achieve pharmacodynamic evidence of on-target activity in normal tissues. The current protocol is appropriately designed to achieve these ends, and the study proceeds without modification. Full article

Intrahepatic cholangiocarcinoma is in most transplant regions a contraindication for liver transplantation, even ruling out an active waiting list registration. However, recent studies showed that well-selected patients after a neo-adjuvant treatment benefit from liver transplantation with good long-term outcomes. The role of living donor liver transplantation is unclear for this indication. The current study focuses on LDLT for intrahepatic cholangiocarcinoma. Full article

We undertook an analysis of the Canadian Agency for Drugs and Technologies in Health (CADTH)’s health technology assessments (HTAs) of systemic therapies for solid tumour indications to determine if a mechanism to re-evaluate HTA decisions is needed based on the level of certainty supporting the original recommendation. To measure the certainty in the evidence, we analysed if: (1) overall survival (OS) was the primary endpoint in the pivotal trial, (2) median OS was available at the time of the recommendation, and (3) the expert review committee explicitly identified gaps in the evidence. There were 96 drugs approved by Health Canada that met our eligibility criteria between 1 January 2017 and 31 October 2021. Median OS was not estimable at the time of the recommendation in 57% of the positive recommendations, and the uncertainty in the magnitude of clinical benefit was identified by the expert review committee in 21% of the positive recommendations. There is uncertainty at the time of the HTA recommendation for many drugs, and thus a need to implement a process to re-evaluate drugs in Canada to allow patients timely access to promising therapies while ensuring long-term value of therapies to patients and the healthcare system. Full article

Background: Cancer therapies targeting actionable molecular alterations (AMA) have developed, but the clinical routine impact of high-throughput molecular profiling remains unclear. We present a monocentric experience of molecular profiling based on liquid biopsy in patients with cancer. Methods: Patients included had solid cancer and underwent cfDNA genomic profiling with FoudationOne Liquid CDx (F1LCDx) test, analyzing 324 genes. Primary endpoint was to describe patients with an AMA for whom clinical decisions were impacted by F1LCDx test results. Results: 191 patients were included, mostly with lung cancer (46%). An AMA was found in 52%. The most common molecular alterations were: TP53 (52%), KRAS (14%) and DNMT3 (11%). The most common AMA were: CHEK2 (10%), PIK3CA (9%), ATM (7%). There was no difference in progression-free survival (2.66 months vs. 3.81 months, p = 0.17), overall survival (5.3 months vs. 7.1 months, p = 0.64), or PFS2/PFS1 ratio ≥ 1.3 (20% vs. 24%, p = 0.72) between patients receiving a molecularly matched therapy (MMT) or a non-MMT, respectively. Patients with a MMT had an overall response rate of 19% and a disease control of 32%. Conclusions: Routine cfDNA molecular profiling is feasible and can lead to the access of targeted therapies. However, no notable benefit in patient’s outcomes was shown in this unselected pan-cancer study. Full article

The safety profile and effectiveness of existing anti-HER2-targeted therapies have not been evaluated in patients with breast cancer and visceral crisis. We report the case of a 26-year-old woman who was diagnosed with advanced HER2-positive breast cancer and initially treated with curative intent therapy in a neoadjuvant setting, using Trastuzumab and Pertuzumab in combination with Docetaxel; her cancer recurred two years later, with liver metastases and pulmonary lymphangitic carcinomatosis, causing visceral crisis. Furthermore, the patient’s clinical status worsened when she developed respiratory failure, hepatomegaly and a severe hepatocytolysis. Since the patient was free of disease more than six months, we started with Paclitaxel half dose because of the hepatic dysfunction, and we gradually reintroduced Trastuzumab and then Pertuzumab. In the meantime, the patient changed her lifestyle by increasing her consumption of fresh fruits and vegetables and fiber and reducing her intake of processed meat, dairy and sugar. As a result, the patient showed a significant improvement in her respiratory symptoms and liver tests in less than two months. Imaging reevaluation showed partial remission of liver metastases and pulmonary lymphangitic carcinomatosis. She underwent seven months of dual anti-HER2 blockade before relapsing cerebrally. Our results suggest that the sequential combination therapy with Trastuzumab, Pertuzumab and Paclitaxel presented in this study, associated with a healthy lifestyle, may be a good management for recurrent HER2-positive breast cancer with pulmonary visceral crisis and severe liver dysfunction. Full article

Emergency department (ED) use is a concern for surgery patients, physicians and health administrators particularly during a pandemic. The objective of this study was to assess the impact of the pandemic on ED use following cancer-directed surgeries. This is a retrospective cohort study of patients undergoing cancer-directed surgeries comparing ED use from 7 January 2018 to 14 March 2020 (pre-pandemic) and 15 March 2020 to 27 June 2020 (pandemic) in Ontario, Canada. Logistic regression models were used to (1) determine the association between pandemic vs. pre-pandemic periods and the odds of an ED visit within 30 days after discharge from hospital for surgery and (2) to assess the odds of an ED visit being of high acuity (level 1 and 2 as per the Canadian Triage and Acuity Scale). Of our cohort of 499,008 cancer-directed surgeries, 468,879 occurred during the pre-pandemic period and 30,129 occurred during the pandemic period. Even though there was a substantial decrease in the general population ED rates, after covariate adjustment, there was no significant decrease in ED use among surgical patients (OR 1.002, 95% CI 0.957–1.048). However, the adjusted odds of an ED visit being of high acuity was 23% higher among surgeries occurring during the pandemic (OR 1.23, 95% CI 1.14–1.33). Although ED visits in the general population decreased substantially during the pandemic, the rate of ED visits did not decrease among those receiving cancer-directed surgery. Moreover, those presenting in the ED post-operatively during the pandemic had significantly higher levels of acuity. Full article

Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies. Full article

Introduction: Minimally invasive surgery has been increasingly used in the treatment of gastric cancer. While laparoscopic gastrectomy has become standard therapy for early-stage gastric cancer, especially in Asian countries, the use of minimally invasive techniques has not attained the same widespread acceptance for the treatment of more advanced tumours, principally due to existing concerns about its feasibility and oncological adequacy. We aimed to examine the safety and oncological effectiveness of laparoscopic technique with radical intent for the treatment of patients with locally advanced gastric cancer by comparing short-term surgical and oncologic outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy at two Western regional institutions. Methods: The trial was designed as a retrospective comparative matched case-control study for postoperative pathological diagnoses of locally advanced gastric carcinoma. Between January 2015 and September 2021, 120 consecutive patients who underwent curative-intent laparoscopic gastrectomy with D2 lymph node dissection were retrospectively recruited and compared with 120 patients who received open gastrectomy. In order to obtain a comparison that was as homogeneous as possible, the equal control group of pairing (1:1) patients submitted to open gastrectomy who matched those of the laparoscopic group was statistically generated by using a propensity matched score method. The following potential confounder factors were aligned: age, gender, Body Mass Index (BMI), comorbidity, ASA, adjuvant therapy, tumour location, type of gastrectomy, and pT stage. Patient demographics, operative findings, pathologic characteristics, and short-term outcomes were analyzed. Results: In the case-control study, the two groups were clearly comparable with respect to matched variables, as was expected given the intentional primary selective criteria. No statistically significant differences were revealed in overall complications (16.7% vs. 20.8%, p = 0.489), rate of reoperation (3.3% vs. 2.5%, p = 0.714), and mortality (4.2% vs. 3.3%, p = 0.987) within 30 days. Pulmonary infection and wound complications were observed more frequently in the OG group (0.8% vs. 4.2%, p < 0.01, for each of these two categories). Anastomotic and duodenal stump leakage occurred in 5.8% of the patients after laparoscopic gastrectomy and in 3.3% after open procedure (p = 0.072). The laparoscopic approach was associated with a significantly longer operative time (212 vs. 192 min, p < 0.05) but shorter postoperative length of stay (9.1 vs. 11.6 days, p < 0.001). The mean number of resected lymph nodes after D2 dissection (31.4 vs. 33.3, p = 0.134) and clearance of surgical margins (97.5% vs. 95.8%, p = 0.432) were equivalent between the groups. Conclusion: Laparoscopic gastrectomy with D2 nodal dissection appears to be safe and feasible in terms of perioperative morbidity for locally advanced gastric cancer, with comparable oncological equivalency with respect to traditional open surgery. Full article

Lung cancer is the leading cause of cancer death in Canada and a significant cause of morbidity for patients and their loved ones. There have been rapid advances in preventing, screening and treating this disease. Here, we present a contemporary review of treatment of non-small cell lung cancer in Canada based on current best practices. The focus of this review is to highlight recent data in screening for lung cancer, management of patients with early and locally-advanced non-small cell lung cancer, as well as management of patients with metastatic disease. There is a special focus on the incorporation of immunotherapy into practice and its associated toxicities. Full article

Endocrine therapy (ET) for hormone receptor-positive (HR+) breast cancer can contribute to gynecologic symptoms (GS) that impact vaginal health, sexual function, and quality of life (QoL). A cross-sectional study was conducted at St. Michael’s Hospital in Toronto, Canada between July 2017 and June 2018 to examine the occurrence and frequency of GS among HR+ breast cancer patients on ET, patient-provider communication, female sexual dysfunction (FSD), and QoL. A Treatment Experience questionnaire was developed for this study and the Female Sexual Function Index (FSFI) and Menopause-Specific Quality of Life questionnaire (MENQOL) were also administered. Of 151 patients surveyed, 77 (51.0%) were on tamoxifen and 74 (49.0%) on an aromatase inhibitor. Most patients (84.1%, 95% confidence interval [CI] 77.3% to 89.5%) experienced at least one GS “all the time” or “often”, or one or more infections, in the past year. Only 44 (31.9%) patients reported that their oncologist had ever previously asked them about experiencing GS. The prevalence of FSD was 61.2% (95% CI 46.2% to 74.8%) among 49 sexually active patients that completed the FSFI. Symptoms captured in the MENQOL’s vasomotor domain were deemed most bothersome. Side effect management and patient-provider communication should be prioritized to optimize GS, vaginal health, and sexual function of ET users. Full article

A standard curative intent approach of chemotherapy treatment for metastatic testicular cancer has been well established. However, there is little guidance for patients undergoing hemodialysis (HD) who require chemotherapy for this disease. Thus, we describe our treatment approach and rationale for a patient on HD with poor risk metastatic nonseminomatous germ cell tumor involving the testicle, lymph nodes, liver, and bone. After orchiectomy, five cycles of cisplatin and modified dose etoposide were delivered and strategically timed with HD. Treatment was complicated by significant neuropathy. Surgical resection of two liver lesions was performed after chemotherapy. Ten years post-chemotherapy, he remains free of clinical, biochemical, or radiological recurrence. While our patient remains free of disease after this treatment, the optimal chemotherapy and dialysis dose and schedule to maximize cure and minimize toxicity remains unknown. Full article

The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer. Full article

Colorectal cancer (CRC) is one of the most common cancers worldwide. Accurate early detection and diagnosis, comprehensive assessment of treatment response, and precise prediction of prognosis are essential to improve the patients’ survival rate. In recent years, due to the explosion of clinical and omics data, and groundbreaking research in machine learning, artificial intelligence (AI) has shown a great application potential in clinical field of CRC, providing new auxiliary approaches for clinicians to identify high-risk patients, select precise and personalized treatment plans, as well as to predict prognoses. This review comprehensively analyzes and summarizes the research progress and clinical application value of AI technologies in CRC screening, diagnosis, treatment, and prognosis, demonstrating the current status of the AI in the main clinical stages. The limitations, challenges, and future perspectives in the clinical implementation of AI are also discussed. Full article