Current Oncology

Background: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. Methods: This study used the SEER data (1974–2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. Results: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value < 0.05, FDR < 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. Conclusion: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM. Full article

Patients with advanced pancreatic cancer (APC) experience many disease-related symptoms. ESAS-r measures the severity of 9 symptom domains and has been validated for use in the ambulatory oncology setting. We aimed to describe symptom burden at baseline for patients with APC treated with modern chemotherapy (CT), and to determine whether symptom burden at baseline is prognostic. Patients diagnosed with APC between 2012–2016, treated with ≥1 cycle of CT, who completed ≥1 ESAS-r were identified. Descriptive statistics were used to report symptom burden and common moderate-to-severe symptoms. A joint model was used to describe the trajectory of ESAS-r during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Of 123 patients identified, the median age was 65 and 61% had metastatic disease. The median baseline ESAS-r total symptom distress score (TSDS) was 24. A total of 86% of patients had at least one symptom score of ≥4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Median overall survival was 10.2 months. Baseline TSDS was not predictive for worse survival in the era of modern CT. Patients with APC have a high burden of cancer-associated symptoms and a high prevalence of moderate-to-severe symptoms. Early intervention has the potential to improve quality of life in this group of patients and should be investigated. Full article

Introduction: Treatment algorithms for small cell lung cancer (SCLC) are determined largely by the Veterans Affairs Lung Cancer Staging Group (VALCSG) staging (limited (LS) versus extensive (ES) stage). Relapse occurs frequently; however, patterns of relapse, in particular the competing risk of thoracic and central nervous system relapse, are not well described. This study describes patterns of relapse in SCLC patients treated at a large tertiary institution in Ontario, Canada. Materials and Methods: A retrospective cohort of SCLC patients treated at the Juravinski Cancer Centre was reviewed. Data were abstracted from the medical record on demographic, disease, treatment and outcome variables. The primary outcome was a description of the patterns of relapse stratified by disease stage. Multivariate analysis was performed to identify prognostic variables for thoracic and CNS relapse. Results: Two hundred and twenty nine patients were treated during the study period (LS—83, ES—146). Relapse occurred in the majority of patients (isolated thoracic—28%, isolated CNS—9%, extrathoracic—9%, thoracic/extrathoracic—14%, systemic and CNS—13%). The median OS was consistent with published data (LS—21.8 months, ES—8.9 months). ES disease and elevated LDH were prognostic for increased thoracic relapse, whereas poor PS and older age were prognostic for lower central nervous system (CNS) relapse. Discussion: Thoracic relapse and CNS relapse represent competing risks for patients with SCLC. Decisions about incorporating thoracic or CNS radiation are complex. More research is needed to incorporate performance status and LDH into treatment algorithms. Full article

Cancer stem cells (CSCs) are accountable for the progress of head and neck squamous cell carcinoma (HNSCC). This exploratory study evaluated the expression of molecular CSC markers in different tissues of HNSCC patients. Tissue specimens of primary tumor, lymph node metastases and macroscopically healthy mucosa of 12 consecutive HNSCC patients, that were treated with surgery and adjuvant radio(chemo)therapy upon indication, were collected. Samples were assessed for the expression of p16 as a surrogate for HPV-related disease and different molecular stem cell markers (ALDH1A1, BCL11B, BMI-1, and CD44). In the cohort, seven patients had HPV-related HNSCC; six thereof were oropharyngeal squamous cell carcinoma. While expression of BMI-1 and BCL11B was significantly lower in healthy mucosa than both tumor and lymph node metastasis, there were no differences between tumor and lymph node metastasis. In the HPV-positive sub-cohort, these differences remained significant for BMI-1. However, no significant differences in these three tissues were found for ALDH1A1 and CD44. In conclusion, this exploratory study shows that CSC markers BMI-1 and BCL11B discriminate between healthy and cancerous tissue, whereas ALDH1A1 and CD44 were expressed to a comparable extent in healthy mucosa and cancerous tissues. Full article

Studies have identified integrated interdisciplinary care as a hallmark of effective palliative care. Although models attempt to show how integration may function, there is little literature available that practically explores how integration is fostered and maintained. In this study we asked palliative care clinicians across Canada to comment on how services are integrated across the healthcare system. This is an analysis of qualitative data from a larger study, wherein clinicians provided written responses regarding their experiences. Content analysis was used to identify response categories. Clinicians (n = 14) included physicians, a nurse and a social worker from six provinces. They identified the benefits of formalized relationships and collaboration pathways with other services to streamline referral and consultation. Clinicians perceived a need for better training of residents and primary care physicians in the community and more acceptance, shared understanding, and referrals. Clinicians also described integrating well with oncology departments. Lastly, clinicians considered integration a complex process with departmental, provincial, and national involvement. The needs and strengths identified by the clinicians mirror the qualities of successfully integrated palliative care programs globally and highlight specific areas in policy, education, practice, and research that could benefit those in Canada. Full article

We investigated first-line (1L) treatment patterns and predictors of taxane use to better understand the evolving metastatic triple-negative breast cancer (mTNBC) treatment landscape. This retrospective analysis of the Truven Health MarketScan® (Somers, NY, USA) Database included women with mTNBC who received 1L therapy within six months of diagnosis (January 2005–June 2015). Multivariate logistic regression models identified predictors of taxane use, adjusting for prognostic factors. A total of 2,271 women with newly diagnosed mTNBC received 1L treatment during the study period. Half received a 1L taxane (53%), more often in combination than as monotherapy (58% versus 42%), though this varied by specific taxane. Nab-Paclitaxel monotherapy increased substantially after 2010. More recent treatment year (odds ratio, 2.16 (95% CI 1.69–2.76]) and number of metastases (≥3 versus 1: 1.73 (1.25–2.40)) predicted taxane monotherapy versus combination. Having a health maintenance organization versus a preferred provider organization plan predicted less nab-paclitaxel versus paclitaxel (0.32 (0.13–0.80)) or docetaxel (0.30 (0.10–0.89)) use. More recent index year (2011–2015 vs 2005–2010) was the only predictor favoring nab-paclitaxel versus paclitaxel (2.01 (1.26–3.21)) or docetaxel (3.63 (2.11–6.26)). Taxane-containing regimens remained the most common 1L mTNBC treatments. Paclitaxel and nab-paclitaxel use changed substantially over time, with nab-paclitaxel use associated with insurance coverage. Full article

The pelvis is a common site of metastatic bone disease. Peri-acetabular lesions are particularly challenging and can cause severe pain, disability and pathologic fractures. Surgical management of these lesions has historically consisted of cementoplasty for contained lesions and Harrington reconstructions for larger, more destructive lesions. Due to the limitations of these procedures, a number of novel procedures have been developed to manage this challenging problem. Percutaneous techniques—including acetabular screw fixation and cementoplasty augmented with screws—have been developed to minimize surgical morbidity. Recent literature has demonstrated a reliable reduction in pain and improvement in function in appropriately selected patients. Several adjuncts to the Harrington procedure have been utilized in recent years to reduce complication rates. The use of constrained liners and dual mobility bearings have reduced the historically high dislocation rates. Cage constructs and porous tantalum implants are becoming increasingly common in the management of large bony defects and destructive lesions. With novel and evolving surgical techniques, surgeons are presented with a variety of surgical options to manage this challenging condition. Physicians must take into account the patients’ overall health status, oncologic prognosis and anatomic location and extent of disease when developing an appropriate surgical plan. Full article

Background: Herpes zoster (HZ) is strongly associated with decreased immune function, a factor of cancer development. Previous studies suggested inconsistent results regarding the association between HZ and increased cancer risk. We aimed to analyze the association between HZ and specific cancer risk. Methods: Of 134,454 patients diagnosed with HZ between 2002 and 2015, 81,993 HZ patients were matched 1:1 with non-HZ individuals by age, sex, and Charlson comorbidity index. Both groups were examined at 1, 3, and 5 years for cancer diagnosis. A Cox proportional hazard regression model was used to estimate cancer risk in both groups. The postherpetic neuralgia (PHN) and non-HZ groups were compared for specific cancer risk. Results: The HZ group showed a slightly decreased overall cancer risk compared with the non-HZ group (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90–0.97, p = 0.002). The HRs for specific cancer risk were 0.41 (95% CI, 0.33–0.50, p < 0.001); 0.86 (95% CI, 0.81–0.91, p < 0.001); 0.87 (95% CI, 0.78–0.97, p = 0.014); 0.80 (95% CI 0.73–0.87, p < 0.001); 1.20 (95% CI, 1.07–1.34, p = 0.001); and 1.66 (95% CI, 1.35–2.03, p < 0.001) for cancers of the lips, mouth, and pharynx; digestive system; respiratory system; unknown secondary and unspecified sites; thyroid and endocrine glands; and lymphoid and hematopoietic systems, respectively. The HZ with PHN group showed higher HR for specific cancer risk, such as lymphoid and hematopoietic systems (95% CI, 1.27–2.39, p < 0.001). Conclusion: HZ was associated with increased or decreased incidence of specific cancers. PHN further increased the risk of developing certain cancers in HZ patients. Full article

Over the years, there have been significant advances in oncology. However, the rate that therapeutics come to market has increased, while the strength of evidence has decreased. Currently, there is limited understanding about how these uncertainties are managed in provincial funding decisions for cancer therapeutics. We conducted qualitative interviews with six senior officials from four different Canadian provinces (British Columbia, Alberta, Quebec, and Ontario) and a document review of the uncertainties found in submissions to the pan-Canadian Oncology Drug Review (pCODR). Participants reported considerable uncertainty related to a lack of solid clinical evidence (early-phase clinical trials: generalizability, immature data, and the use of unvalidated surrogate outcomes). Proposed strategies to deal with the uncertainty included risk-sharing agreements, collection of real-world evidence (RWE), and ongoing collaboration between federal groups and provinces. The document review added to the reported uncertainties by classifying them into five main categories: trial validity, population, comparators, outcomes, and intervention. This study highlights how decision makers must deal with significant amounts of uncertainty in funding decisions for cancer drugs, most of which stems from methodological limitations in clinical trials. There is a critical need for transparent priority-setting processes and mechanisms to reevaluate drugs to ensure benefit given the high level of uncertainty of novel therapeutics. Full article

Palliative care has an interdisciplinary tradition and Canada is a leader in its research and practice. Yet even in Canada, a full interdisciplinary complement is often lacking, with psychosocial presence ranging from 0–67.4% depending on the discipline and region. We sought to examine the most notable gaps in care from the perspective of Canadian palliative professionals. Canadian directors of palliative care programs were surveyed with respect to interdisciplinary integration. Participants responded in writing or by phone interview. We operationalized reports of interdisciplinary professions as either “present” or “under/not-represented”. The Vaismoradi, Turunen, and Bondas’ procedure was used for content analysis. Our 14 participants consisted of physicians (85.7%), nurses (14.3%), and a social worker (7.1%) from Ontario (35.7%), British Columbia (14.3%), Alberta (14.3%), Quebec (14.3%), Nova Scotia (14.3%), and New Brunswick (7.1%). Psychology and social work were equally and most frequently reported as “under/not represented” (5/14, each). All participants reported the presence of medical professionals (physicians and nurses) and these groups were not reported as under/not represented. Spiritual care and others (e.g., rehabilitation and volunteers) were infrequently reported as “under/not represented”. Qualitative themes included Commonly Represented Disciplines, Quality of Multidisciplinary Collaboration, Commonly Under-Represented Disciplines, and Special Concern: Psychosocial Care. Similar to previous reports, we found that (1) psychology was under-represented yet highly valued and (2) despite social work’s relative high presence in care, our participants reported a higher need for more. These finding highlight those psychosocial gaps in care are most frequently noted by palliative care professionals, especially psychology and social work. We speculate on barriers and enablers to addressing this need. Full article

On behalf of the Canadian Association of Psychosocial Oncology, we are pleased to present the Abstracts from the 2021 Annual Conference, titled “Advocating for All: Psychosocial Oncology at the Intersections of Equity, Diversity, and Inclusion”. The Conference was held virtually from 8 June 2021 to 10 June 2021. This conference brought together key stakeholders including multidisciplinary professionals from nursing, psychology, psychiatry, social work, spiritual care, nutrition, medicine, rehabilitation medicine, occupational health and radiation therapy for both adult and pediatric populations. Participants included clinicians, researchers, educators in cancer care, community-based organizations and patient representatives. Patients, caregivers and family members presented abstracts that speak to their role in managing cancer experiences and care. Over one hundred (100) abstracts were selected for presentation as symposia, 20-min oral presentations, 10-min oral presentations, 90-min workshops and poster presentations. We congratulate all the presenters on their research work and contribution. Full article

Lung metastases are the second most common malignant neoplasms of the lung. It is estimated that 20–54% of cancer patients have lung metastases at some point during their disease course, and at least 50% of cancer-related deaths occur at this stage. Lung metastases are widely accepted to be oligometastatic when five lesions or less occur separately in up to three organs. Stereotactic body radiation therapy (SBRT) is a noninvasive, safe, and effective treatment for metastatic lung disease in carefully selected patients. There is no current consensus on the ideal dose and fractionation for SBRT in lung metastases, and it is the subject of study in ongoing clinical trials, which examines different locations in the lung (central and peripheral). This review discusses current indications, fractionations, challenges, and technical requirements for lung SBRT. Full article

Contrast-enhanced spectral mammography (CESM) is a promising, digital breast imaging method for planning surgeries. The study aimed at comparing digital mammography (MG) with CESM as predictive factors in visualizing multifocal-multicentric cancers (MFMCC) before determining the surgery extent. We analyzed 999 patients after breast cancer surgery to compare MG and CESM in terms of detecting MFMCC. Moreover, these procedures were assessed for their conformity with postoperative histopathology (HP), calculating their sensitivity and specificity. The question was which histopathological types of breast cancer were more frequently characterized by multifocality–multicentrality in comparable techniques as regards the general number of HP-identified cancers. The analysis involved the frequency of post-CESM changes in the extent of planned surgeries. In the present study, MG revealed 48 (4.80%) while CESM 170 (17.02%) MFMCC lesions, subsequently confirmed in HP. MG had MFMCC detecting sensitivity of 38.51%, specificity 99.01%, PPV (positive predictive value) 85.71%, and NPV (negative predictive value) 84.52%. The respective values for CESM were 87.63%, 94.90%, 80.57% and 96.95%. Moreover, no statistically significant differences were found between lobular and NST cancers (27.78% vs. 21.24%) regarding MFMCC. A treatment change was required by 20.00% of the patients from breast-conserving to mastectomy, upon visualizing MFMCC in CESM. In conclusion, mammography offers insufficient diagnostic sensitivity for detecting additional cancer foci. The high diagnostic sensitivity of CESM effectively assesses breast cancer multifocality/multicentrality and significantly changes the extent of planned surgeries. The multifocality/multicentrality concerned carcinoma, lobular and invasive carcinoma of no special type (NST) cancers with similar incidence rates, which requires further confirmation. Full article

The current recommendation to stop colorectal cancer screening for older adults is based on a lack of evidence due to systematic exclusion of this population from trials. Older adults are a heterogenous population with many available strategies for patient-centered assessment and decision-making. Evolutions in management strategies for colorectal cancer have made safe and effective options available to older adults, and the rationale to screen for treatable disease more reasonably, especially given the aging Canadian population. In this commentary, we review the current screening guidelines and the evidence upon which they were built, the unique considerations for screening older adults, new treatment options, the risks and benefits of increased screening and potential considerations for the new guidelines. Full article

Background: Members of the Wnt signaling pathway have been shown to play a role in nasopharyngeal carcinoma (NPC) progression. Aim: The purpose of this study was to investigate WNT8B protein expression in NPC patients using tissue microarray (TMA) analysis and to evaluate its correlation with patient survival and clinical parameters. Methods: A total of 82 NPC cases, together with six normal nasopharyngeal tissue samples, were targeted to construct the TMA blocks. The WNT8B protein expression was evaluated by immunohistochemistry and its correlation to the clinicopathological features was investigated. Results: Sixty-two of 82 (75.6%) cases exhibited high WNT8B protein expression while 20/82 (24.4%) cases appeared to have low WNT8B expression. The univariate analysis revealed that systemic metastasis was associated with patient 5-year survival. The multivariate Cox proportional hazard regression analysis showed that WNT8B expression and systemic metastasis were significantly associated with the survival of NPC patients. Furthermore, there was no correlation found between the WNT8B protein expression and other clinicopathological parameters. Conclusion: Our results suggest that the expression of WNT8B is associated with NPC patients’ survival and could serve as an independent prognostic factor for NPC patients. Full article

Background: Non-compliance and non-persistence with endocrine therapy for breast cancer is common and usually related to treatment-induced side effects. There are anecdotal reports that simply changing the time of day when taking endocrine therapy (i.e., changing morning dosing to evening dosing or vice versa) can reduce side effects. Literature review: We conducted a literature review to evaluate whether changing the timing of tamoxifen and/or aromatase inhibitor administration impacted patient outcomes. No randomized control trials or prospective cohort studies that looked at time of day of endocrine therapy were identified through our review of literature from 1947 until August 2020. Conclusions: Given the rates of endocrine therapy non-compliance and non-persistence reported in the literature, ranging from 41–72% and 31–73%, respectively, simply changing the time of day when medications are taken could be an important strategy. We could identify no trials evaluating the effect of changes in timing of administration of endocrine therapy on breast cancer patient outcomes. Randomized control trials are clearly indicated for this simple and cost-effective intervention. Full article

Background: It is common for biopsies of concerning pulmonary nodules to result in cytologic “atypia” on biopsy, which may represent a benign response or a false negative finding. This investigation evaluated time to diagnosis and factors which may predict an ultimate diagnosis of lung cancer in these patients with atypia cytology on lung nodule biopsy. Methods: This retrospective study included patients of the Stony Brook Lung Cancer Evaluation Center who had a biopsy baseline diagnosis of atypia between 2010 and 2020 and were either diagnosed with cancer or remained disease free by the end of the observation period. Cox Proportional Hazard (CPH) Models were used to assess factor effects on outcomes. Results: Among 106 patients with an initial diagnosis of atypia, 80 (75%) were diagnosed with lung cancer. Of those, over three-quarters were diagnosed within 6 months. The CPH models indicated that PET positivity (SUV ≥ 2.5) (HR = 1.74 (1.03, 2.94)), nodule size > 3.5 cm (HR = 2.83, 95% CI (1.47, 5.45)) and the presence of mixed ground glass opacities (HR = 2.15 (1.05, 4.43)) significantly increased risk of lung cancer. Conclusion: Given the high conversion rate to cancer within 6 months, at least tight monitoring, if not repeat biopsy may be warranted during this time period for patients diagnosed with atypia. Full article

Adjuvant endocrine therapy (AET) is recommended after hormone receptor-positive breast cancer to reduce risk of recurrence, but adherence is sub-optimal in many women. Behavioral interventions have been ineffective in improving adherence rates to AET. This qualitative descriptive study investigates factors that support women in AET use and suggestions for interventions to improve AET use and management. Interviews with women who persisted with AET (n = 23), women who discontinued AET (n = 15), and healthcare providers (HCPs; oncologists, oncology residents, and pharmacists; n = 9) were conducted, transcribed, and described using thematic analysis. Data collection stopped once saturation occurred (i.e., no new codes or themes emerged during interviews). Two researchers created codes and developed themes in an iterative process; a third researcher verified the representativeness of final themes. This study was approved by the Health Research Ethics Board of Alberta (ID: HREBA.CC-17-0513). Women who persisted described being prepared for side effects and having self-management strategies, strong rationale for AET use, supportive HCPs, and available resources as relevant factors. Women who discontinued described feeling overwhelmed by side effects, information needs, drawbacks of AET, helpful/unhelpful experiences with HCPs, and contextual factors as relevant to their discontinuation. HCPs described health system-related and patient-related barriers, side effect management, and patient-provider interactions as relevant to supporting AET use. The considerable overlap in themes among the three groups suggests broad recognition of salient factors relevant to AET use and that associated strategies to improve use may be acceptable to patients and providers alike. Factors supporting AET use could include the following: education (which may be necessary but insufficient), developing a strong personal rationale for use, being prepared for side effects, having side effect management strategies, reciprocal communication between patients and HCPs, and accessible resources. Full article