Curr. Oncol., Volume 29, Issue 4 (April 2022) – 59 articles

Immune checkpoint inhibitors (ICIs) have emerged as novel options that are effective in treating various cancers. They are monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). However, activation of the immune systems through ICIs may concomitantly trigger a constellation of immunologic symptoms and signs, termed immune-related adverse events (irAEs), with the skin being the most commonly involved organ. The dermatologic toxicities are observed in nearly half of the patients treated with ICIs, mainly in the form of maculopapular rash and pruritus. In the majority of cases, these cutaneous irAEs are self-limiting and manageable, and continuation of the ICIs is possible. This review provides an overview of variable ICI-mediated dermatologic reactions and describes the clinical and histopathologic presentation. Early and accurate diagnosis, recognition of severe toxicities, and appropriate management are key goals to achieve the most favorable outcomes and quality of life in cancer patients. Full article

Recently, cytoreductive prostatectomy for metastatic prostate cancer (mPCa) has been associated with improved oncological outcomes. This study was aimed at evaluating whether robot-assisted radical prostatectomy (RARP) as a form of cytoreductive prostatectomy can improve oncological outcomes in patients with mPCa. We conducted a retrospective study of twelve patients with mPCa who had undergone neoadjuvant therapy followed by RARP. The endpoints were biochemical recurrence-free survival, treatment-free survival, and de novo metastasis-free survival. At the end of the follow-up period, none of the enrolled patients had died from PCa. The 1- and 2-year biochemical recurrence-free survival rates were 83.3% and 66.7%, respectively, and treatment-free survival rates were 75.0% and 56.3%, respectively. One patient developed de novo bone metastases 6.4 months postoperatively, and castration-resistant prostate cancer 8.9 months postoperatively. After RARP, the median duration of recovery of urinary continence was 5.2 months. One patient had severe incontinence (>2 pads/day) 24 months postoperatively. RARP may be a treatment option in patients with mPCa who have achieved a serum prostate-specific antigen level < 0.2 ng/mL, and present without new lesions on imaging. Full article

The aim of this qualitative study was to identify the motivational factors that influence cancer survivors to participate and adhere to the fear of cancer recurrence (FCR) FORT randomized controlled trial (RCT). Fifteen women diagnosed with breast and gynecological cancer who took part in the FORT RCT were interviewed about their experience to consent and adhere to the trial. The transcribed interviews were content analyzed within a relational autonomy framework. The analysis revealed that the participants’ motivation to consent and adhere to the FORT RCT was structured around thirteen subthemes grouped into four overarching themes: (1) Personal Influential Factors; (2) Societal Motivations; (3) Structural Influences; and (4) Gains in Emotional Support. The unique structures of the trial such as the group format, the friendships formed with other participants in their group and with the group leaders, and the right timing of the trial within their cancer survivorship trajectory all contributed to their motivation to consent and adhere to the FORT RCT. While their initial motivation to participate was mostly altruistic, it was their personal gains obtained over the course of the trial that contributed to their adherence. Potential gains in emotional and social support from psycho-oncology trials should be capitalized when approaching future participants as a mean to improve on motivations to consent and adhere. Full article

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year (the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting). Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecological malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future. Full article

(1) Background: Glioblastoma multiforme (GBM) shows complex mechanisms of spreading of the tumor cells, up to remote areas, and little is still known of these mechanisms, thus we focused on MRI abnormalities observable in the tumor and the brain adjacent to the lesion, up to the contralateral hemisphere, with a special interest on tensor diffusion imaging informing on white matter architecture; (2) Material and Methods: volumes, macroscopic volume (MV), brain-adjacent-tumor (BAT) volume and abnormal color-coded DTI volume (aCCV), and region-of-interest samples (probe volumes, ipsi, and contra lateral to the lesion), with their MRI characteristics, apparent diffusion coefficient (ADC), fractional anisotropy (FA) values, and number of fibers (DTI fiber tracking) were analyzed in patients suffering GBM (n = 15) and metastasis (n = 9), and healthy subjects (n = 15), using ad hoc statistical methods (type I error = 5%) (3) Results: GBM volumes were larger than metastasis volumes, aCCV being larger in GBM and BAT ADC was higher in metastasis, ADC decreased centripetally in metastasis, FA increased centripetally either in GBM or metastasis, MV and BAT FA values were higher in GBM, ipsi FA values of GBM ROIs were higher than those of metastasis, and the GBM ipsi number of fibers was higher than the GBM contra number of fibers; (4) Conclusions: The MV, BAT and especially the aCCV, as well as their related water diffusion characteristics, could be useful biomarkers in oncology and functional oncology. Full article

Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related death. The high mortality and morbidity associated with EOC are mostly due to late diagnosis and chemotherapy drug resistance. Currently, the standard first-line chemotherapy regimen is systemic administration of platinum-based chemotherapy combined with a taxane. A major problem besides cisplatin resistance (occurring in nearly one-third of patients) is the greater toxicity of the drug combinations. A synergistic treatment with drug supporting activity could maximize the cytotoxic effects of chemotherapeutic agents on tumor cells while decreasing the dosage of each drug to potentially reduce toxicity. The ALDH-blocking agent Disulfiram (DSF), a clinically approved drug used for alcoholism treatment, has displayed promising anti-cancer activity. We previously described that blocking ALDH activity enhances the induction of apoptosis, especially in ovarian cancer stem cells treated with chemotherapeutic agents. In this study, we further investigated the synergistic effect of DSF in combination with cytotoxic chemotherapeutic drugs. The concentration of each chemotherapeutic agent could be significantly reduced with sustained efficacy on tumor cell apoptosis in cell lines in vitro (Dose-Reduction Index at IC₅₀ from 1 to 50). Moreover, the potential chemo-sensitizing effects of DSF on ALDH-associated cisplatin-resistant ovarian cancer stem cells were also investigated and shown that in contrast to its high resistance to cisplatin, the cisplatin-resistant cells remain very sensitive to DSF-induced cytotoxicity (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 60.4% vs. 20.5%). In combination with DSF and cisplatin, relatively more apoptosis and necrosis were induced in cisplatin-resistant cells than in their parental cells (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 81.5% vs. 50.1%). A transcriptome analysis identified that ALDH was mainly enriched in the cancer-associated fibroblasts and showed that ALDH plays roles in responding to oxidative stress, metabolisms, and energy transition in the ALDH-associated cisplatin-resistant ovarian cancer stem cells. In conclusion, our data demonstrate a key role of ALDH-associated cisplatin-resistant cancer stem cells and identifies DSF as a potential adjuvant for a rational protocol design by computational quantitative assessment in vitro on ovarian cancer cell lines. Our work contributes to resolving the ALDH-associated cisplatin resistance and provides a resource for the development of novel chemotherapeutic regimens. Full article

The BC-brain questionnaire was developed by BC Cancer to detect health problems in patients with central nervous system (CNS) tumours in routine clinical care, treated with radiotherapy (RT), as part of the Prospective Outcomes and Support Initiative (POSI). This study aimed to present and validate the BC-brain questionnaire in patients with brain metastases (BrM) treated with RT. The BC-brain questionnaire was constructed with three subscales: mobility, thinking and CNS symptoms. Patients with BrM from five BC Cancer centres completed this questionnaire at first visit and subsequent follow-up appointments. A total of 365 patients finished the first and 105 finished the follow-up questionnaire. Summary scores of each subscale were calculated. Mobility, thinking and subtotal score showed good reliability with Cronbach’s α > 0.7. Multitrait scaling analysis showed good convergent and divergent validity. The correlations between subscales ranged from 0.262 to 0.456 for baseline and from 0.378 to 0.597 for follow-up. Patients on dexamethasone had worse performance. Patients with a KPS of </=70 had worse performance than patients with a KPS of >70. In general, this BC-brain questionnaire has good reliability and validity, and is proper to use as an option for a patient-reported outcome (PRO) instrument to measure the quality of life in BrM patients treated with RT. Full article

Patients with chronic lymphocytic leukemia (CLL) relapsing on ibrutinib are often treated with the Bcl-2 inhibitor venetoclax. However, the transition from one agent to another poses some clinical challenges due to disease flares sometimes occurring right after ibrutinib interruption. Here, we describe three clinical vignettes highlighting two distinct patterns of ibrutinib-to-venetoclax transition. While patients following the favorable pattern transited to venetoclax without experiencing disease flare, the one patient who took the unfavorable path showed rapid disease rebound, with large-cell transformation occurring one week after ibrutinib interruption. A high burden of BTK and PLCG2 mutations was found only in patients with the favorable transition pattern, suggesting that removing BTK inhibition might be particularly harmful if CLL cells are progressing through mechanisms external to the BTK axis. Full article

(1) Background: In literature, approximately 20% of mCRPC present somatic DNA damage repair (DDR) gene mutations, and their relationship with response to standard therapies in mCRPC is not well understood. The objective was to evaluate outcomes of mCRPC patients treated with standard therapies according to somatic DDR status. (2) Methods: Eighty-three patients were recruited at Caen Cancer Center (France). Progression-free survival (PFS) after first-line treatment was analyzed according to somatic DDR mutation as primary endpoint. PFS according to first exposure to taxane chemotherapy and PFS2 (time to second event of disease progression) depending on therapeutic sequences were also analyzed. (3) Results: Median first-line PFS was 9.7 months in 33 mutated patients and 8.4 months in 50 non-mutated patients (p = 0.9). PFS of first exposure to taxanes was 8.1 months in mutated patients and 5.7 months in non-mutated patients (p = 0.32) and significantly longer among patients with ATM/BRCA1/BRCA2 mutations compared to the others (10.6 months vs. 5.5 months, p = 0.04). PFS2 was 16.5 months in mutated patients, whatever the sequence, and 11.7 months in non-mutated patients (p = 0.07). The mutated patients treated with chemotherapy followed by NHT had a long median PFS2 (49.8 months). (4) Conclusions: mCRPC patients with BRCA1/2 and ATM benefit from standard therapies, with a long response to taxanes. Full article

We aimed to assess whether the ongoing course of the COVID-19 epidemic has been associated with an increased risk of adverse pathology (AP) findings in prostate cancer (PC) patients treated with radical prostatectomy (RP). We performed a retrospective data analysis which included 408 consecutive, non-metastatic, previously untreated PC patients who underwent RP in our institution between March 2020 and September 2021. Patients were divided into two equally numbered groups in regard to the median surgery date (Early Epidemic [EE] and Late Epidemic [LE]) and compared. Adverse pathology was defined as either grade group (GG) ≥ 4, pT ≥ 3a or pN+ at RP. Patients in the LE group demonstrated significantly higher rates of AP than in the EE group (61 vs. 43% overall and 50 vs. 27% in preoperative non-high-risk subgroup, both p < 0.001), mainly due to higher rates of upgrading. On multivariable analysis, consecutive epidemic week (odds ratio: 1.02, 95% confidence interval: 1.00–1.03, p = 0.009) as well as biopsy GG ≥ 2 and a larger prostate volume (mL) were associated with AP in non-high-risk patients. The study serves as a warning call for increased awareness of risk underassessment in contemporarily treated PC patients. Full article

EBV-positive mucocutaneous ulcer (EBV-MCU) was classified as a rare new entity of the lymphoproliferative B-cell diseases by the WHO in 2017 and must be distinguished from head and neck squamous cell carcinoma by early biopsy. The aim of the study is to raise awareness of the disease and to give a review of the current literature and a recommendation for EBV-MCU management. All EBV-MCU cases of the head and neck region published so far were included. We also report a case of a pharyngeal EBV-MCU in an 89-year-old patient who was immunosuppressed by chronic lymphatic leukaemia/small lymphocytic lymphoma (CLL/SLL). In contrast to all previously described cases, histopathology showed a co-infiltration of EBV-MCU and CLL/SLL. A total of 181 cases were identified on PubMed and summarised. EBV-MCU was predominantly caused by immunosuppressive drug therapy. Complete remission could be achieved in 68% of cases and was mainly attributed to a reduction of the immunosuppressive therapy alone (72%). However, some severe cases require more aggressive treatment. Regarding the various histopathologic similarities to other lymphoproliferative disorders, the diagnosis of EBV-MCU can be misleading, with a great impact on patient care and treatment. This diagnosis must be made with caution and requires a combination of clinical, morphological and immunophenotypic features. Full article

Cancer patients and their families experience considerable financial hardship; however, the current published literature on the economic burden of cancer at the population level has typically focused on the costs from the health system’s perspective. This study aims to estimate the economic burden of cancer in Canada from a societal perspective. The analysis was conducted using the OncoSim-All Cancers model, a Canadian cancer microsimulation model. OncoSim simulates cancer incidence and deaths using incidence and mortality data from the Canadian Cancer Registry and demography projections from Statistics Canada. Using a phase-based costing framework, we estimated the economic burden of cancer in Canada in 2021 by incorporating published direct health system costs and patients’ and families’ costs (out-of-pocket costs, time costs, indirect costs). From a societal perspective, cancer-related costs were CAD 26.2 billion in Canada in 2021; 30% of costs were borne by patients and their families. The economic burden was the highest in the first year after cancer was diagnosed (i.e., initial care). During this time, patients and families’ costs amounted to almost CAD 4.8 billion in 2021. This study provides a comprehensive estimate of the economic burden of cancer, which could inform cost–benefit analyses of proposed cancer prevention interventions. Full article

The advent of anti-HER2 targeted therapies has dramatically improved the outcome of HER2-positive breast cancer; however, resistance to treatment in the metastatic setting remains a challenge, highlighting the need for novel therapies. The arrival of new treatment options and clinical trials examining the efficacy of novel agents may improve outcomes in the metastatic setting, including in patients with brain metastases. In the first-line setting, we can potentially cure a selected number of patients treated with pertuzumab + trastuzumab + taxane. In the second-line setting, clinical trials show that trastuzumab deruxtecan (T-DXd) is a highly effective option, resulting in a shift from trastuzumab emtansine (T-DM1) as the previous standard of care. Moreover, we now have data for patients with brain metastases to show that tucatinib + trastuzumab + capecitabine can improve survival in this higher-risk group and be an effective regimen for all patients in the third-line setting. Finally, we have a number of effective anti-HER2 therapies that can be used in subsequent lines of therapy to improve patient outcomes. This review paper discusses the current treatment options and presents a practical treatment sequencing algorithm in the context of the Canadian landscape. Full article

The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We retrospectively analysed data from 128 patients (pts) with GC and OAC who underwent surgery in the context of multimodal treatment with PC. We collected data on WL during different steps of therapy together with other histopathologic and demographic information. We analysed the effects on overall survival (OS) and disease-free survival (DFS). Results: Pts with WL ≥ 5% during neoadjuvant chemotherapy exhibited significantly worse OS compared with pts with WL < 5% (median OS: 23.6 months [95% CI: 4.4–42.9] vs. 63.5 months [95% CI: 50.7–76.2], p = 0.007) and DFS (median DFS: 12.5 months [95% CI: 2.9–22.1] vs. 63.5 months [95% CI: 31.6–95.4], p = 0.016). Pts with WL ≥ 14% during the whole treatment exhibited significantly worse OS compared with pts with WL < 14% (median OS: 43.7 months [95% CI: 13.2–74.2] vs. not reached, p = 0.028) and DFS (median DFS: 34.3 months [95% CI: 14.0–54.5] vs. not reached, p = 0.038). Conclusion: WL patterns during neoadjuvant chemotherapy and during the whole treatment correlate with a significantly worse prognosis in operated pts with curative GC or OAC in the context of a multimodal treatment with PC. A validation of this prognostic effect in prospective studies is warranted. Full article

This study aimed to establish a prognosis-prediction model based on serological indicators in patients with epithelial ovarian cancer (EOC). Patients initially diagnosed as ovarian cancer and surgically treated in Fudan University Shanghai Cancer Center from 2014 to 2018 were consecutively enrolled. Serological indicators preoperatively were collected. A risk model score (RMS) was constructed based on the levels of serological indicators determined by receiver operating characteristic curves. We correlated this RMS with EOC patients’ overall survival (OS). Finally, 635 patients were identified. Pearson’s χ² results showed that RMS was significantly related to clinical parameters. Kaplan–Meier analysis demonstrated that an RMS less than 3 correlated with a longer OS (p < 0.0001). Specifically, significant differences were perceived in the survival curves of different subgroups. Multivariate Cox analysis revealed that age (p = 0.015), FIGO stage (p = 0.006), ascites (p = 0.015) and RMS (p = 0.005) were independent risk factors for OS. Moreover, RMS combined with age, FIGO and ascites could better evaluate for patients’ prognosis in DCA analyses. Our novel RMS-guided classification preoperatively identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method, meaning that it could be a useful and economical tool for tailored monitoring and/or therapy. Full article

Cancer-related cognitive impairment (CRCI) has been frequently reported in colorectal cancer survivors. Heparan sulfate (HS) was gradually considered to be related to cognitive disorders. The effect and potential mechanism of HS on CRCI in colorectal cancer patients were unexplored. In this study, all participants were divided into a cognitive impaired group and a cognitive normal group. The concentrations of oxidative stress factors and HS in serum were detected. Associations among HS, oxidative stress factors and CRCI were evaluated. Participants with cognitive impairment exhibited increased levels of HS, GSH, SOD and MDA, compared to the patients with normal cognitive performance. The independent significant association was found between HS and CRCI after controlling for various covariates. The higher concentrations of HS were related to the decreased cognitive performance among survivors who reported higher levels of GSH (β = 0.080, p = 0.002). Moreover, the nonlinear association between the level of HS and cognitive scores was confirmed using the restricted cubic splines (p < 0.001). These results indicated that the increased concentrations of circulating HS had a nonlinear negative connection with cognitive performance in colorectal cancer survivors, which was moderated by GSH. HS might be a new biomolecule for the identification and management of patients with CRCI. Full article

As the rates of cancer incidence and survival increase in Canada, more patients are living in the post-treatment survivorship phase of their cancer journey. Identifying cancer survivors’ concerns and unmet needs is important so that health care teams can provide relevant information, supports, and resources. Secondary data analysis was carried out on the Alberta patient sample from the 2016 Pan-Canadian Transitions Study survey, designed by the Canadian Partnership Against Cancer. The top concerns for patients treated for five different cancers were examined descriptively and compared. A question about information that patients received post-treatment was also descriptively analyzed. Binary logistic regressions were conducted for each tumour group, using the top three concerns for each group as outcomes and a variety of demographic factors as independent variables. There were 1833 valid respondents in the Alberta sample. Fatigue and anxiety were top concerns for multiple tumour groups. Most patients received more information about treatment side effects than about signs of recurrence and community resources. Within certain tumour groups, younger patients had higher odds of having concerns, particularly anxiety. Awareness of the common and unique concerns experienced by cancer survivors post-treatment enables health care providers to tailor care and resources to help patients manage their symptoms and concerns. These findings address gaps in knowledge around the cancer survivorship phase and may be applicable to cancer programs and primary care providers in Alberta and beyond. Full article

Radiation-induced fibrosis (RIF) is a severe side effect related with soft tissues sarcomas (STS) radiotherapy. RIF is a multicellular process initiated primarily by TGF-β1 that is increased in irradiated tissue, whose signaling leads to intracellular Smad2/3 phosphorylation and further induction of profibrotic target genes. P144 (Disetertide©) is a peptide inhibitor of TGF-β1 and is proposed as a candidate compound for reducing RIF associated wound healing problems and muscle fibrosis in STS. Methods: A treatment and control group of WNZ rabbits were employed to implement a brachytherapy animal model, through catheter implantation at the lower limb. Two days after implantation, animals received 20 Gy isodosis, intended to induce a high RIF grade. The treatment group received intravenous P144 administration following a brachytherapy session, repeated at 24–72 h post-radiation, while the control group received placebo. Four weeks later, affected muscular tissues underwent histological processing for collagen quantification and P-Smad2/3 immunohistochemistry through image analysis. Results: High isodosis Brachytherapy produced remarkable fibrosis in this experimental model. Results showed retained macro and microscopical morphology of muscle in the P144 treated group, with reduced extracellular matrix fibrosis, with a lower area of collagen deposition measured through Masson’s trichrome staining. Intravenous P144 also induced a significant reduction in Smad2/3 phosphorylation levels compared with the placebo group. Conclusions: P144 administration clearly reduces RIF and opens a new potential co-treatment approach to reduce complications in soft tissue sarcoma (STS) radiotherapy. Further studies are required to establish whether the dosage and timing optimization of P144 administration, in different RIF phases, might entirely avoid fibrosis associated with STS brachytherapy. Full article

Salvage chemotherapy for patients with unresectable pancreatic cancer (UR-PC) who have been treated with gemcitabine and nab-paclitaxel (GnP), and 5-fluorouracil (5-FU)/l-leucovorin (LV) plus nanoliposomal irinotecan (nal-IRI), has not been fully established. We retrospectively reviewed data from 17 patients with UR-PC who initiated 5-FU/l-LV plus oxaliplatin (FOLFOX) as salvage chemotherapy at our hospital between June 2020 and August 2021, after treatment with GnP and 5-FU/LV plus nal-IRI. The primary endpoint was tumor response. The secondary endpoints were progression-free survival (PFS) and adverse events (AEs). The response and disease control rates were 5.9% (1/17) and 17.6% (3/17), respectively. The median PFS was 1.8 months (range: 0.4–5.2 months). Eight patients (47.1%) experienced grade 3 nonhematologic AEs, while none experienced grade 3 hematologic AEs. Two patients with controlled disease had homologous recombination deficiency (HRD)-associated gene mutations in cancer panel testing. The FOLFOX regimen benefit for UR-PC patients treated with GnP and 5-FU/LV plus nal-IRI may be limited to patients with HRD-associated gene mutations. Full article

Background: Despite meticulous surgery for non-small cell lung cancer (NSCLC), relapse is as high as 70% at 5 years. Many institutions do not conduct reflexive molecular testing on early stage specimens, although targeted gene therapy may extend life by years in the event of recurrence. This ultimately delays definitive treatment with additional biopsy risking suboptimal tissue acquisition and quality for molecular testing. Objective: To compare molecular profiles of genetic alterations in early and late NSCLC to provide evidence that reflexive molecular testing provides clinically valuable information. Methods: A single-center propensity matched retrospective analysis was conducted using prospectively collected data. Adults with early and late-stage NSCLC had tissue subject to targeted panel-based NGS. Frequencies of putative drivers were compared, with 1:3 matching on the propensity score; p < 0.05 deemed statistically significant. Results: In total, 635 NSCLC patients underwent NGS (59 early, 576 late); 276 (43.5%) females; age 70.9 (±10.2) years; never smokers 140 (22.0%); 527 (83.0%) adenocarcinomas. Unadjusted frequencies of EGFR mutations were higher in the early cohort (30% vs. 18%). Following adjustment for sex and smoking status, similar frequencies for both early and late NSCLC were observed for variants in EGFR, KRAS, ALK, MET, and ROS1. Conclusion: The frequency of clinically actionable variants in early and late-stage NSCLC was found to be similar, providing evidence that molecular profiling should be performed on surgical specimens. This pre-determined profile is essential to avoid treatment delay for patients who will derive clinical benefit from targeted systemic therapy, in the high likelihood of subsequent relapse. Full article

Severe pain is frequent in patients with locally advanced pancreatic ductal adenocarcinoma (PDCA). Stereotactic body radiotherapy (SBRT) provides high local control rates in these patients. The aim of this review was to systematically analyze the available evidence on pain relief in patients with PDCA. We updated our previous systematic review through a search on PubMed of papers published from 1 January 2018 to 30 June 2021. Studies with full available text, published in English, and reporting pain relief after SBRT on PDCA were included in this analysis. Statistical analysis was carried out using the MEDCALC statistical software. All tests were two-sided. The I² statistic was used to quantify statistical heterogeneity (high heterogeneity level: >50%). Nineteen papers were included in this updated literature review. None of them specifically aimed at assessing pain and/or quality of life. The rate of analgesics reduction or suspension ranged between 40.0 and 100.0% (median: 60.3%) in six studies. The pooled rate was 71.5% (95% CI, 61.6–80.0%), with high heterogeneity between studies (Q² test: p < 0.0001; I² = 83.8%). The rate of complete response of pain after SBRT ranged between 30.0 and 81.3% (median: 48.4%) in three studies. The pooled rate was 51.9% (95% CI, 39.3–64.3%), with high heterogeneity (Q² test: p < 0.008; I² = 79.1%). The rate of partial plus complete pain response ranged between 44.4 and 100% (median: 78.6%) in nine studies. The pooled rate was 78.3% (95% CI, 71.0–84.5%), with high heterogeneity (Q² test: p < 0.0001; I² = 79.4%). A linear regression with sensitivity analysis showed significantly improved overall pain response as the EQD2α/β:10 increases (p: 0.005). Eight papers did not report any side effect during and after SBRT. In three studies only transient acute effects were recorded. The results of the included studies showed high heterogeneity. However, SBRT of PDCA resulted reasonably effective in producing pain relief in these patients. Further studies are needed to assess the impact of SBRT in this setting based on Patient-Reported Outcomes. Full article

Objective: The purpose of this guideline is to determine the clinical utility of multigene profiling assays in individuals with early-stage invasive breast cancer. Methods: This guideline was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care (PEBC) through a systematic review of relevant literature, patient- and caregiver-specific consultation and internal and external reviews. Recommendation 1: In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and the Breast Cancer Index) to help guide the use of systemic therapy. Recommendation 2: In patients with early-stage node-negative ER-positive/HER2-negative disease, clinicians may use a low-risk result from Oncotype DX, MammaPrint, Prosigna, EndoPredict/EPclin, or Breast Cancer Index assays to support a decision not to use adjuvant chemotherapy. Recommendation 3: In patients with node-negative ER-positive/HER2-negative disease, clinicians may use a high-risk result from Oncotype DX to support a decision to offer chemotherapy. A high Oncotype DX recurrence score is capable of predicting adjuvant chemotherapy benefit. Recommendation 4: In postmenopausal patients with ER-positive/HER2-negative tumours and one to three nodes involved (N1a disease), clinicians may withhold chemotherapy based on a low-risk Oncotype DX or MammaPrint score if the decision is supported by other clinical, pathological, or patient-related factors. Recommendation 5: The evidence to support the use of molecular profiling to select the duration of endocrine therapy is evolving. In patients with ER-positive disease, clinicians may consider using a Breast Cancer Index (H/I) high assay result to support a decision to extend adjuvant endocrine therapy if the decision is supported by other clinical, pathological, or patient-related factors. Full article

Skin cancer is one of the most common cancers worldwide and the number of patients is steadily increasing. In skin cancer care, greater interdisciplinary cooperation is required for prevention, early detection, and new complex systemic therapies. However, the implementation of innovative medical care is a major challenge, especially for rural regions with an older than average, multimorbid population, with limited mobility, that are long distances from medical facilities. Solutions are necessary to ensure comprehensive oncological care in rural regions. The aim of this study was to identify indicators to establish a regional care network for integrated skin cancer care. To capture the perspectives of different stakeholder groups, we conducted two focus groups with twenty skin cancer patients and their relatives, a workshop with eight physicians, and three semi-structured interviews with health insurance company representatives. Qualitative data were recorded, transcribed, and analyzed following Mayring’s content analysis methods. We generated ten categories based on the reported optimization potentials; five categories were assigned to all three stakeholder groups: Prevention and early diagnosis, accessibility of physicians/clinics, physicians’ resources, care provider’s responsibilities, and information exchange. The results indicate the need for stronger integration of care in the region. They provide the basis for regional networking as, for example, the conception of treatment pathways or telemedicine with the aim to improve a comprehensive skin cancer care. Our study should raise awareness and postulate as a demand that all patients receive guideline-based therapy, regardless of where they live. Full article

Psychological distress is more common in cancer survivors than the general population, and is associated with adverse outcomes. This cross-sectional study aimed to assess the relationship between socioeconomic status (SES), race and psychological distress, using data from a nationally representative sample of cancer survivors in the United States. Outcomes of interest were mild, moderate, and severe psychological distress as assessed by the Patient Health Questionnaire-4 (PHQ-4). In our univariate model, there was no statistically significant difference in the PHQ-4 scores of Caucasian and African American respondents. On the other hand, a lower SES correlated with a higher likelihood of psychological distress, and this persisted in our multivariate model. This study brings additional awareness to the negative impact of a lower socioeconomic status on mental health outcomes in cancer survivors, and further highlights the importance of the timely identification and screening of individuals at a high risk of psychological distress, in order to limit missed opportunities for relevant mental health interventions in this population. Full article

Hippocampal-sparing brain radiotherapy (HS-BRT) in cancer patients results in preservation of neurocognitive function after brain RT which can contribute to patients’ quality of life (QoL). The crucial element in HS-BRT treatment planning is appropriate contouring of the hippocampus. Ten doctors delineated the left and right hippocampus (LH and RH, respectively) on 10 patients’ virtual axial images of brain CT fused with T1-enhanced MRI (1 mm) according to the RTOG 0933 atlas recommendations. Variations in the spatial localization of the structure were described in three directions: right–left (X), cranio-caudal (Y), and forward–backward (Z). Discrepancies concerned three-dimensional localization, shape, volume and size of the hippocampus. The largest differences were observed in the first three delineated cases which were characterized by larger hippocampal volumes than the remaining seven cases. The volumes of LH of more than half of hippocampus contours were marginally bigger than those of RH. Most differences in delineation of the hippocampus were observed in the area of the posterior horn of the lateral ventricle. Conversely, a large number of hippocampal contours overlapped near the brainstem and the anterior horn of the lateral ventricle. The most problematic area of hippocampal contouring is the posterior horn of the lateral ventricle. Training in the manual contouring of the hippocampus during HS-BRT treatment planning under the supervision of experienced radiation oncologists is necessary to achieve optimal outcomes. This would result in superior outcomes of HS-BRT treatment and improvement in QoL of patients compared to without HS-BRT procedure. Correct delineation of the hippocampus is problematic. This study demonstrates difficulties in HS-BRT treatment planning and highlights critical points during hippocampus delineation. Full article

Laser interstitial thermal therapy (LITT) has become an increasingly utilized alternative to surgical resection for the treatment of glioma in patients. However, treatment outcomes in isocitrate dehydrogenase 1 and 2 (IDH1/2) mutant glioma, specifically, have not been reported. The objective of this study was to characterize a single institution’s cohort of IDH1/2 mutant grade 2/3 glioma patients treated with LITT. We collected data on patient presentation, radiographic features, tumor molecular profile, complications, and outcomes. We calculated progression-free survival (PFS) and tested factors for significant association with longer PFS. Overall, 22.7% of our cohort experienced progression at a median follow up of 1.8 years. The three- and five-year estimates of PFS were 72.5% and 54.4%, respectively. This is the first study to characterize outcomes in patients with IDH1/2 mutant glioma after LITT. Our results suggest that LITT is an effective treatment option for IDH1/2 mutant glioma. Full article

Approximately 20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), providing an actionable target for many different therapies. In the metastatic setting, prognosis has improved greatly with the use of anti-HER2 drugs such as trastuzumab, pertuzumab, and trastuzumab-emtansine. In the third line setting and beyond, several emerging treatments have shown benefits, including novel small molecule targeted agents and antibody-drug conjugates. Systemic treatment of brain metastases in HER2-positive patients and the role of endocrine-based treatment for patients with hormone receptor (HR) positive disease remain areas of research interest. This article will review the current approach to systemic management of metastatic HER2-positive breast cancer in Canada, and present novel treatments that may be available in the near future. Full article

Background: In this study, we compared and contrasted design characteristics, results, and publications of randomized controlled trials (RCTs) in gastrointestinal (GI), lung, and breast cancer. Methods: A PUBMED search identified phase III RCTs of anticancer therapy in GI, lung, and breast cancer published globally during the period 2014–2017. Descriptive statistics, chi-square tests, and the Kruskal–Wallis test were used to compare RCT design, results, and output across the cancer sites. Results: A total of 352 RCTs were conducted on GI (36%), lung (29%), and breast (35%) cancer. Surrogate endpoints were used in 55% of trials; this was most common in breast trials (72%) compared to GI (47%) and lung trials (43%, p < 0.001). Breast trials more often met their primary endpoint (54%) than GI (41%) and lung trials (41%) (p = 0.024). When graded with the ESMO-MCBS, lung cancer trials (50%, 15/30) were more likely to meet the threshold for substantial benefit. GI trials were published in journals with a substantially lower impact factor (IF; median IF 13) than lung (median IF 21) and breast cancer trials (median IF 21) (p = 0.038). Conclusions: Important differences in RCT design and output exist between the three major cancer sites. Use of surrogate endpoints and the magnitude of benefit associated with new treatments vary substantially across cancer sites. Full article

Surgical resection remains the only curative treatment strategy for Pancreatic Ductal Adenocarcinoma (PDAC). A proportion of patients succumb to early disease recurrence post-operatively despite receiving adjuvant chemotherapy. The ability to identify these high-risk individuals at their initial diagnosis, prior to surgery, could potentially alter their treatment algorithm. This unique patient cohort may benefit from neo-adjuvant chemotherapy, even in the context of resectable disease, as this may secure systemic control over their disease burden. It may also improve patient selection for surgery. Using the Cancer Genome Atlas dataset, we first confirmed the poor overall survival associated with early disease recurrence (p < 0.0001). The transcriptomic profiles of these tumours were analysed, and we identified key aberrant signalling pathways involved in early disease relapse; downregulation across several immune signalling pathways was noted. Differentially expressed genes that could serve as biomarkers were identified (BPI, C6orf58, CD177, MCM7 and NUDT15). Receiver operating characteristic curves were constructed in order to identify biomarkers with a high diagnostic ability to identify patients who developed early disease recurrence. NUDT15 expression had the highest discriminatory capability as a biomarker (AUC 80.8%). Its expression was confirmed and validated in an independent cohort of patients with resected PDAC (n = 13). Patients who developed an early recurrence had a statistically higher tumour expression of NUDT15 when compared to patients who did not recur early (p < 0.01). Our results suggest that NUDT15 can be used as a prognostic biomarker that can stratify patients according to their risk of developing early disease recurrence. Full article

Epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) can result in significant skin toxicities that may impact patients’ quality of life. While these skin reactions are well documented in patients with lighter skin, there is a paucity of literature and images to guide clinicians in their assessment in patients with darker skin tones. Given that dermatological reactions in patients with darker skin are not well represented, this can result in the undertreatment or mistreatment of these otherwise common toxicities. Herein, we present a case of a female patient with a darker skin tone with metastatic non-small cell lung carcinoma (NSCLC) with EGFR-TKI-related skin toxicity and her clinical course. Full article