Single-cell spatial immune landscapes of primary and metastatic brain tumours.

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.

The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy.

Background: Programmed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell carcinoma (ASCC). The objectives of this study were to measure the expression of PD-L1 and CD8 in patients with ASCC treated with radical chemoradiotherapy (CRT) and to correlate tumor expression with progression-free survival (PFS) and overall survival (OS). Methods: Ninety-nine patients with ASCC treated with primary CRT at two tertiary care cancer centers between 2000 and 2013, with available pre-treatment tumors, were included. Tissue microarrays (TMAs) from pre-treatment tumor specimens were stained for PD-L1 and CD8. PD-L1 expression in the tumor and stroma was quantified using HALO image analysis software, and results were interpreted using quantitative methods. The density of CD8 cells within the tumor was interpreted by a trained pathologist semi-quantitatively, using a 0-4 scoring system. Kaplan-Meier analysis with log-rank was used to determine the significance in the association of tumor markers with PFS and OS. Cox multivariate analysis was used to explore independent predictors of PFS and OS. Results: Of the 99 patients, 63 (64%) had sufficient tumor samples available for full analysis. CD8 high status was documented in 32 of 63 (50.8%) % of cases. PD-L1 expression was positive in 88.9% of cases. Approximately half the patients had tumor PD-L1 ≥ 5%. Patients with tumor PD-L1 ≥ 5% had better OS vs those with lower expression, HR=0.32 (95% CI 0.11-0.87), p=0.027; 10 years OS: 84% for tumor PD-L1 ≥ 5% vs 49% for PD-L1 < 5%. PD-L1 expression was not associated with PFS. On multivariate analysis, tumor PD-L1 ≥ 5% showed a trend to statistical significance for better OS, HR=0.55 (95% CI 0.12- 1.00), p=0.052. Conclusions: Tumor PD-L1≥5% is associated with OS in patients with ASCC treated with CRT. PD-L1 expression status using this unique cut-point warrants further validation for prognostication in patients with this disease. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status.

ACE-Neuro: A tailored exercise oncology program for neuro-oncology patients - Study protocol.

Background: Patients with primary brain tumours (i.e., neuro-oncology patients) lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise - Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness. Methods: Neuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro and other cancer rehabilitation services (including physiatry, physiotherapy, occupational therapy, and exercise physiology). In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes and functional fitness, and objective physical activity tracked across the 12-week program. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching. Conclusion: We are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.

Developing a clinical-pathologic model to predict genomic risk of recurrence in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative, node negative breast cancer.

INTRODUCTION: Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative, node negative (NN) breast cancer may be offered a gene expression profiling (GEP) test to determine recurrence risk and benefit of adjuvant chemotherapy. We developed a clinical-pathologic (CP) model to predict genomic recurrence risk and examined its performance characteristics. METHODS: Patients diagnosed with HR-positive, HER2-negative, NN breast cancer with a tumour size < 30 mm and who underwent a GEP test [OncotypeDX or Prosigna] in Alberta from October 2017 through March 2019 were identified. Patients were classified as low or high genomic risk. Multivariable logistic regression analysis was performed to examine the associations of CP factors with genomic risk. A CP model was developed using coefficients of regression and sensitivity analyses were performed. RESULTS: A total of 366 patients were eligible (135 were tested using OncotypeDX and 231 with Prosigna). Of these, 64 (17.5%) patients were classified as high genomic risk. On multivariable logistic regression, tumour size > 20 mm (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.84-6.98; P<0.001), low expression of progesterone receptor (OR, 3.46; 95% CI, 1.76-6.82; P<0.001), and histological grade III (OR, 7.24; 95% CI, 3.82-13.70; P<0.001) predicted high genomic risk. A CP model using these variables was developed to provide a score of 0-4. A CP cut-point of 0, identified 56% of genomic low risk patients with a specificity of 98.4%. CONCLUSIONS: A CP model could be used to narrow the population of breast cancer patients undergoing GEP testing.

Breast cancer in transgender female-to-male individuals: A case report of androgen receptor-positive breast cancer.

Highlight the challenges associated with managing breast cancer in female-to-male (FtM) transgender individuals. This is a rare entity, requiring nuanced decision-making regarding surgery as well as adjuvant therapies given the unique hormonal environment seen in individuals taking exogenous androgen as part of their gender identity. Contemporary case report derived from our clinical experience. Discussion focuses on a brief summation of all known cases of female-to-male breast cancer in FtM individuals described in the literature. A 48-year-old FtM transgender individual on exogenous testosterone for 19 years with stage IIA (pT1cN1M0), ER+(8/8), PR+(8/8), Androgen Receptor(AR)+(5%-8%), Her-2-negative invasive ductal carcinoma of the breast. Due to AR positivity in tumor, cessation of testosterone was chosen after careful consideration of potential ramifications from both a cancer treatment as well as gender identity standpoint. Endocrinology consultation reassured the patient that identity affirming changes of facial hair growth and voice depth would persist after cessation of testosterone. Patient did not wish to undergo chemotherapy and as such was treated with combination of radiation to the axilla, adjuvant Anastrozole and testosterone cessation. Although breast cancer is rare in FtM transgender individuals, it can occur. Many FtM individuals take exogenous testosterone. It is important to test the tumor for the androgen receptor as this may have important implications for both gender identity and treatment. Additionally, the mastectomy commonly performed for "top" surgery in this population is not adequate for oncologic control by itself and at present there is no guidance regarding postsurgical screening in this population, especially in those individuals with a strong family history of breast cancer.

Paraneoplastic neuropsychiatric syndrome presenting as delirium.

Delirium in patients with cancer is associated with poor outcomes, but reversible causes need to be ruled out. We report the case of a 59-year-old woman who was presented with behavioural and cognitive changes over 2 weeks. She was non-verbal and combative, requiring involuntary admission and declaration of incompetence to make healthcare treatment decisions. Infectious and metabolic investigations and initial brain imaging were unremarkable. She was diagnosed with limited-stage small cell lung cancer and a paraneoplastic neuropsychiatric syndrome. Owing to the patient's delirium, chemotherapy delivery required pharmacological and physical restraints. After 2 cycles of chemotherapy, she could participate in the decision process and was discharged home. She completed radical chemo-radiotherapy and has remained free of disease progression for 18 months. Paraneoplastic neuropsychiatric syndromes, although rare, are potentially treatable and need to be excluded as a cause of delirium.

Social Media Use Among Physicians and Trainees: Results of a National Medical Oncology Physician Survey.

PURPOSE: Cancer management requires coordinated care from many health care providers, and its complexity requires physicians be up to date on current research. Web-based social media support physician collaboration and information sharing, but the extent to which physicians use social media for these purposes remains unknown. The complex field of oncology will benefit from increased use of online social media to enhance physician communication, education, and mentorship. To facilitate this, patterns of social media use among oncologists must be better understood. METHODS: A nine-item survey investigating physician social media use, designed using online survey software, was distributed via e-mail to 680 oncology physicians and physicians in training in Canada. Responses were analyzed using descriptive statistics. RESULTS: A total of 207 responses (30%) were received; 72% of respondents reported using social media. Social media use was highest, at 93%, in respondents age 25 to 34 years and lowest, at 39%, in those age 45 to 54 years. This demonstrates a significant gap in social media use between younger users and mid- to late-career users. The main barrier to use was lack of free time. CONCLUSION: The identified gap in social media use between age cohorts may have negative implications for communication in oncology. Despite advancements in social media and efforts to integrate social media into medical education, most oncologists and trainees use social media rarely, which, along with the age-related gap in use, may have consequences for collaboration and education in oncology. Investigations to further understand barriers to social media use should be undertaken to enhance physician collaboration and knowledge sharing through social media.

Population based analysis ependymoma patients in Alberta from 1975 to 2007.

BACKGROUND: Ependymomas are rare tumors of the central nervous system whose management is controversial. This population-based study of adults and children with ependymoma aims to (1) identify clinical and treatment-related factors that impact survival and (2) determine if postoperative radiotherapy (RT) can improve survival of patients with subtotal resection (STR) to levels similar to patients who had gross total resection (GTR). METHODS: This retrospective population-based study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in Alberta, Canada. RESULTS: Younger patients (<7 years of age) were more likely to be diagnosed with grade III tumors compared with adults in whom grade I tumors were more common (p=0.003). Adults were more likely to have spinally located tumors compared to young children whose tumors were typically found in the brain. Overall, young children with ependymoma were more likely to die than older children or adults (p=0.001). An equivalent number of patients underwent GTR as compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor location, lower grade, and GTR were associated with improved progression free survival but only GTR was associated with significant improvement in overall survival. Median survival after STR and RT was 82 months compared with 122 months in patients who had GTR (p=0.0022). CONCLUSIONS: This is the first Canadian population-based analysis of patients with ependymoma including adults and children. Extent of resection appears to be the most important factor determining overall survival. Importantly, the addition of RT to patients initially treated with STR does not improve survival to levels similar to patients receiving GTR.

The prognostic value of HPV status and p16 expression in patients with carcinoma of the anal canal.

BACKGROUND: In anal cancer studies, the detection frequency of high-risk HPV (human papillomavirus) is variable, depending on the method used. There are limited data reporting results of different HPV detection techniques in the same clinical series, and very few correlating results with clinical outcome. OBJECTIVES: To evaluate tumor expression of p16/HPV16 using three different methods, and to determine their association with clinical outcome in patients with anal canal squamous cell carcinomas (SCC). DESIGN: This retrospective study included patients with anal canal SCC treated with definitive radiotherapy or chemoradiotherapy at a single institution between 1992 and 2005. Formalin-fixed paraffin-embedded tumor samples from 53 of the 89 (60%) patient pre-treatment biopsies were adequate for tissue microarray construction. HPV status was determined using: p16 expression by conventional immunohistochemistry (IHC) and quantitative IHC (AQUA), HPV genotype analysis by chromogenic in situ hybridization (CISH) and HPV linear array sub-typing. Expression status was correlated with clinical outcome. RESULTS: 80% (28/35) of patient tumors had high p16 expression using conventional IHC. HPV16 CISH was positive in 81% (34/42) of tumors, and 78% (28/36) of tumors were HPV subtype 16. HPV16 CISH correlated with p16 evaluated by conventional IHC (correlation coefficient 0.46; p = 0.01) and by p16 AQUA score (correlation coefficient 0.49; p = 0.001). A subset of cases (15%) had very high p16 quantitative IHC scores (>244) and were associated with a higher incidence of local or distant recurrence (p = 0.04). CONCLUSIONS: The vast majority (80%) of anal canal SCC in our series were positive for HPV16/p16, regardless of the testing method used. The exploratory analysis of automated quantitative IHC scoring was the only technique to define a subset of patients with a worse prognosis by p16 expression status on univariate analysis. Further exploration of the molecular mechanisms of treatment resistance in association with very high p16 expression is warranted.

Initial treatment patterns over time for anaplastic oligodendroglial tumors.

Anaplastic oligodendroglial tumors are rare neoplasms with no standard approach to treatment. We sought to determine patterns of treatment delivered over time and identify clinical correlates of specific strategies using an international retrospective cohort of 1013 patients diagnosed from 1981-2007. Prior to 1990, most patients received radiotherapy (RT) alone as initial postoperative treatment. After 1990, approximately 50% of patients received both RT and chemotherapy (CT) sequentially and/or concurrently. Treatment with RT alone became significantly less common (67% in 1980-1984 vs 5% in 2005-2007, P < .0001). CT alone was more frequently administered in later years (0% in 1980-1984 vs 38% in 2005-2007; P < .0001), especially in patients with 1p19q codeleted tumors (57% of codeleted vs 4% with no deletion in 2005-2007; P < .0001). Temozolomide replaced the combination of procarbazine, lomustine, and vincristine (PCV) among patients who received CT alone or with RT (87% vs 2% in 2005-2007). In the most recent time period, patients with 1p19q codeleted tumors were significantly more likely to receive CT alone (with temozolomide), whereas RT with temozolomide was a significantly more common treatment strategy than either CT or RT alone in cases with no deletion (P < .0001). In a multivariate polytomous logistic regression model, the following were significantly associated with type of treatment delivered: date (5-year interval) of diagnosis (P < .0001), 1p19q codeletion (P < .0001), pure anaplastic oligodendroglioma histology (P < .01), and frontal lobe predominance (P < .05). Limited level 1 evidence is currently available to guide treatment decisions, and ongoing phase III trials will be critical to understanding the optimal therapy.

Extended adjuvant temozolomide for treatment of newly diagnosed glioblastoma multiforme.

The standard of care for newly diagnosed glioblastoma multiforme (GBM) is temozolomide (TMZ) chemotherapy given concurrently with radiation for 6 weeks followed by 6 months of adjuvant TMZ. Originally, patients in Alberta were treated with only six cycles of adjuvant TMZ regardless of clinical status but institutional policy was amended to allow up to 12 cycles of adjuvant therapy for patients experiencing at least stable disease and minimal toxicity. We conducted a population-based analysis to determine if extended adjuvant TMZ treatment (i.e., more than six cycles) confers a survival advantage as compared to the standard six cycles for newly diagnosed GBM patients. Patient data was collected from the Alberta Cancer Registry and patient charts. Progression free--and overall survival was determined in patients receiving six cycles of adjuvant TMZ and compared with that of patients receiving more than six cycles. Patients in whom adjuvant chemotherapy was stopped at cycle six experienced a median survival of 16.5 months, whereas, those who received more than six cycles survived for 24.6 months (p = 0.031). Extended adjuvant therapy was not associated with increased toxicity. In multivariate analysis, adjuvant monthly Temozolomide for more than six cycles was an independent prognostic factor for both progression free--and overall survival. These data suggest extended adjuvant temozolomide (i.e., more than six cycles) should be considered in patients with newly diagnosed GBM.

Remisión completa y prolongada de un carcinoma inflamatorio de mama diseminado / Complete and prolonged remission of a disseminated inflammatory carcinoma of the breast

El carcinoma inflamatorio de mama representa 1-4 por ciento de todos los cánceres mamarios presentándose 30-35 por ciento en estadio diseminado. La sobrevida a 4 años es del 10 por ciento con sobrevida mediana de 23,4 meses. Comunicamos la evolución de una paciente portadora de un carcinoma inflamatorio de la mama diseminado, que tras tratamiento sistémico con quimio-hormonoterapia ha permanecido libre de enfermedad por 20 años. En la evolución desarrolla un carcinoma endometrial bien diferenciado, estadio I, tratado quirúrgicamente y sin evidencia de recaída tras 8 años libre de enfermedad

Carcinomatosis meníngea en tumores sólidos / Meningeal carcinomatosis in solid tumors

La carcinomatosis meníngea es una rara complicación en la evolución de los tumores sólidos; constituye una entidad de difícil diagnóstico y aún controvertido manejo terapéutico. Se presenta en este trabajo una casuística de 12 pacientes con diagnóstico de meningosis carcinomatosa en tumores sólidos; se comentan y discuten los principales aspectos clínicos, paraclínicos y terapéuticos de esta patología