Current Oncology

A valid treatment option for recurrence after definite radiotherapy (RT) for localized prostate cancer (PC) is salvage radical prostatectomy (SRP). However, data on SRP are scarce, possibly resulting in an underutilization. A systematic review was performed using MEDLINE (Pubmed), Embase, and Web of Science databases including studies published between January 1980 and April 2020. Overall, 23 English language articles including a total number of 2323 patients were selected according to PRISMA criteria. The overall median follow-up was 37.5 months (IQR 35.5–52.5). Biochemical-recurrence (BCR)-free probability ranged from 34% to 83% at five years, respectively, and from 31% to 37% at 10 years. Cancer specific survival (CSS) and overall survival (OS) ranged from 88.7% to 98% and 64% to 95% at five years and from 72% to 83% and 65% to 72% at 10 years, respectively. Positive surgical margins ranged from 14% to 45.8% and pathologic organ-confined disease was reported from 20% to 57%. The rate of pathologic > T2-disease ranged from 37% to 80% and pN1 disease differed between 0% to 78.4%. Pre-SRP PSA, pre-SRP Gleason Score (GS), pathologic stage after SRP, and pathologic lymph node involvement seemed to be the strongest prognostic factors for good outcomes. SRP provides accurate histopathological and functional outcomes, as well as durable cancer control. Careful patient counseling in a shared decision-making process is recommended. Full article

Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, PIK3CA. The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer. Methods: Published genomic data and associated clinical data from TCGA cervical cancer cohort were analyzed at cBioportal for amplifications in genes at 3q26. The clinical and molecular characteristics of the group of patients with 3q26 amplifications was compared with the group without 3q26 amplifications. Comparative prevalence of amplification and expression of genes at 3q26 in amplified squamous cervical cancer cases were surveyed as well as 3q26 amplifications in cervical cancer cell line databases. Results: Amplification of 3q26 locus is a prevalent molecular lesion in cervical squamous cell carcinomas encountered in about 15% of cases in TCGA cohort of 247 patients. Cancer-related genes commonly amplified from 3q26 include PIK3CA, TBL1XR1, DCUN1D1, SOX2, MECOM, PRKCI, and TERC. Amplified cases do not completely overlap with PIK3CA mutant cases. Differences exist between 3q26-amplified and non-amplified carcinomas in the frequency of mutations and frequency of other amplifications. Most commonly over-expressed genes in 3q26 amplified cases include PIK3CA, TBL1XR1, DCUN1D1, and less commonly SOX2 and PRKCI. Conclusion: The subset of squamous cervical carcinomas with 3q26 amplifications is not overlapping with cancers carrying PIK3CA mutations and contains, besides PIK3CA, other cancer-associated genes that are over-expressed at the mRNA level, including TBL1XR1 and DCUN1D1. DCUN1D1, a regulator of SCF ubiquitin ligase activity, may be a relevant pathogenic player given the importance of ubiquitination and the proteasome in the disease. These observations could form the basis for therapeutic exploitation in this subset of squamous cervical carcinomas. Full article

Background: This review aimed to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis using meta-analysis and trial sequential analysis, as well as to assess the quality of the results by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Methods: A comprehensive search of three databases including Medline, Embase and Central was performed to identify randomized controlled trials that used oral cryotherapy for the prevention of chemotherapy-induced oral mucositis. The primary outcome was the incidence of oral mucositis for trials employing oral cryotherapy as the intervention for the prevention of oral mucositis. The meta-analysis was performed using the random-effects model and random errors of the meta-analyses were detected by trial sequential analysis. Results: A total of 14 RCTs with 1577 participants were included in the present meta-analysis. Patients treated with oral cryotherapy were associated with a significantly lower risk of developing oral mucositis of any grade (risk ratio (RR), 0.67 (95% CI: 0.56–0.81, p < 0.05)). Findings from the subgroup analyses showed that oral cryotherapy significantly reduced the risk of oral mucositis in patients undergoing bone marrow transplantation (RR 0.69, CI: 0.54–0.89, p < 0.05) as well as chemotherapy (RR 0.66, CI: 0.58–0.75, p < 0.05). Findings from the trial sequential analysis suggested that the evidence on oral cryotherapy as a preventive intervention for oral mucositis in patients with solid malignancies receiving conventional chemotherapy was conclusive. Conclusion: Oral cryotherapy is effective in preventing oral mucositis in patients undergoing chemotherapy for the management of solid malignancies. The use of oral cryotherapy in preventing oral mucositis in bone marrow transplantation settings showed promising efficacy, but the evidence is not conclusive and requires more high-quality randomized controlled trials. Full article

The focus on cancer rehabilitation has increased, but breast cancer patients still report unmet rehabilitation needs. Since many women today will live long beyond their diagnosis, there are multiple challenges for the healthcare system in supporting these women in their new life situation. A more individualized approach is seen as necessary to optimize the rehabilitation for survivors. Pathographies, i.e., autobiographical or biographical accounts of experiences of illness, expose us to personal accounts of the journey through illness and treatment, offering us details, emotions, phrasings, and imagery from an individual perspective. In this literary study, we have analyzed two contemporary Swedish-speaking pathographies about breast cancer. In our analysis, we have presented perspectives on survivorship, and the authors’ ways of conveying their breast cancer experiences through narrative. The pathographies envision the prominent impact the breast cancer has on the authors’ lives. Narratives of survivorship have the potential to complement the more general medical knowledge with their nuanced and multifaceted stories of breast cancer. Learning from this type of material may improve the understanding of the complexity of breast cancer survivorship issues. This may be a way to become more attuned to identifying individual needs and preferences of breast cancer patients. Full article

The Canadian Cancer Clinical Trials Network (3CTN) was established in 2014 to address the decline in academic cancer clinical trials (ACCT) activity. Funding was provided to cancer centres to conduct a Portfolio of ACCTs. Larger centres received core funding and were paired with smaller centres to enable support and sharing of resources. All centres were eligible for incentive-based funding for recruitment above pre-3CTN baseline. Established performance measures were collected and tracked. The overall recruitment target was 50% above pre-3CTN baseline by Year 4. An analysis was completed to identify predictive success factors and descriptive statistics were used to summarize site characteristics and outcomes. From 2014–2018, a total of 11,275 patients were recruited to 559 Portfolio trials, an overall increase of 59.6% above pre-3CTN baseline was observed in Year 4. Twenty-five (51%) adult centres met the Year 4 recruitment target and the overall recruitment target was met within three years. Three factors that correlated with sites’ achieving recruitment targets were: time period, region and number of baseline trials. 3CTN was successful in meeting its objectives and will continue to support ACCTs and member cancer centres, monitor performance over time and seek continued funding to ensure success, better trial access and outcomes for patients. Full article

Peptide receptor radionuclide therapy (PRRT) is used to treat patients with advanced malignant pheochromocytomas (PCCs) and paragangliomas (PGLs). Patients are at risk of a PRRT-induced catecholamine crisis, and standard guidelines regarding the prevention and management of infusion reactions are lacking. In this case series, the institutional experience of five sequential patients with metastatic PCCs and PGLs receiving PRRT on an outpatient basis is described, of which four had symptomatic tumors and three had a high burden of disease. All patients with symptomatic tumors were treated with preventive management prior to the initiation of PRRT, and no infusion reactions or catecholamine crises were documented. PRRT may be delivered safely on an outpatient basis for patients with metastatic PCCs and PGLs with the involvement of an interdisciplinary team. Full article

Background: Recent large population-based studies have shed light on an association between prostate cancer (PCa) survivorship and mental health, which emerged when the comparison group was either men without a history of cancer or those with any other type of cancer except prostate. Here we examine the role of surgery alone, compared to other types of treatment modalities in this association in a population-based sample of men with prostate or other types of cancer. Methods: A cross-sectional analysis was conducted on a subsample of 632 male participants aged 36–69 from the 2009–2015 survey cycle of the Atlantic PATH cohort study. The primary outcomes were the presence of mild, moderate or severe depression or anxiety indicators and were assessed using the seven-item generalized anxiety disorder (GAD-7) scale and the nine-item Patient Health Questionnaire (PHQ-9), respectively. The presence of a lifetime history of PCa or other form of cancer (except PCa) was the main predictor variable and was assessed in cancer treatment modality (surgery or other types of treatment modalities) stratified analyses. Covariates included age, marital status, household income, comorbidity, and survivorship time. Results: The presence of depression in this sample was prevalent among 17.7% of men, and of anxiety among 9.3% of men. Survivors who were treated with surgery for their PCa diagnosis had 7.55 statistically significantly higher odds of screening positive for current depression symptoms compared with those of other forms of cancer in controlled analyses. These differences were not observed for anxiety. Conclusions: These findings emphasize the need for multidisciplinary survivorship care plans among PCa patients, especially those who undergo surgery. Targeted programming aimed at prioritizing and delivering comprehensive mental health support to PCa survivors early in the survivorship journey is justified. Full article

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