Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: Long-Term Clinical Outcomes.

Purpose: For early-stage non-small cell lung cancer, surgery is the preferred approach in operable patients, whereas SABR is preferred for patients who are medically inoperable. The combination of neoadjuvant SABR followed by surgery was tested in the Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer (MISSILE) phase 2 trial. We report long-term outcomes beyond 5 years of follow-up.

Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Final Results of the ORATOR Randomized Trial.

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation).

Merkel cell carcinoma mimicking acute leukemia.

Bone marrow aspirate showed diffuse infiltration by a population of monomorphic cells with scant cytoplasm, markedly increased nuclear-to-cytoplasmic ratio, and numerous indistinct nucleoli. Bone marrow biopsy confirmed extensive marrow infiltration by a malignant neoplasm with strong and diffuse expression of synaptophysin by immunohistochemistry, consistent with metastases from Merkel Cell carcinoma.

Case Report: Prolonged remission of metastatic cisplatin-refractory nasopharyngeal carcinoma with Pembrolizumab.

Background: Epstein-Barr virus (EBV)-related nasopharyngeal cancer (NPC) is a common type of cancer in certain areas of the world such as southeast Asia, but is uncommon in Canada. There is currently no reliably effective standard treatment for incurable metastatic EBV-related NPC that progresses after first-line therapy with gemcitabine/cisplatin.

Methods: With his consent, the health records of a patient with relapsed metastatic EBV-related NPC treated with pembrolizumab immunotherapy were retrospectively reviewed and reported.

Efficacy and feasibility of 3D printed redesigned Venezia™ applicator for treating advanced cervix and recurrent endometrial cancer.

Purpose: Venezia™ is an interstitial brachytherapy applicator for treating advanced cervical and vaginal vault recurrent cancer. However, there are limitations that lead to suboptimal target coverage. 3D printing introduction allows the redesign of Venezia™ for bulky and irregular-shaped tumors.

Resection of a Large Hemorrhagic Mediastinal Lymphangioma in an Adult Patient: A Radiologic-Pathologic Correlation.

Lymphangiomas are rare benign lesions resulting from abnormal proliferation and sequestration of lymphatic tissues that are disconnected from the rest of the lymphatic system. This is a case of a 50-year-old woman with an unusually large mediastinal lymphangioma complicated by hemorrhage. The substantial mass effect and unstable clinical status necessitated urgent operative management.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown.

Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC.

Design, Setting, And Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020.

Characterising the use of surgical pathology rush requests: a descriptive analysis and survey.

This study aimed to characterise priority or 'rush' surgical pathology requests and identify potentially targetable factors. We performed a retrospective descriptive analysis of rush requests at our institution from 2016 to 2019 and conducted a survey asking pathologists about their perspectives on rush cases. There were 3677 rush cases, with case characteristics generally stable over the study period.

Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial.

Purpose: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking.

Validation of the risk stratification score in idiopathic pulmonary fibrosis: study protocol of a prospective, multi-centre, observational, 3-year clinical trial.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a poor prognosis, with a progressive decline in lung function and considerable variability in the disease's natural history. Besides lung transplantation (LTx), the only available treatments are anti-fibrosing drugs, which have shown to slow down the disease course. Therefore, predicting the prognosis is of pivotal importance to avoid treatment delays, which may be fatal for patients with a high risk of progression.

Canadian ROS proto-oncogene 1 study (CROS) for multi-institutional implementation of ROS1 testing in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all advanced stage non-squamous NSCLC patients be also tested for ROS1 gene rearrangements. Several studies have suggested that ROS1 immunohistochemistry (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung cancers, with assays showing high sensitivity but moderate to high specificity.

Overcoming the Challenges of High Quality RNA Extraction from Core Needle Biopsy.

The use of gene expression profiling (GEP) in cancer management is rising, as GEP can be used for disease classification and diagnosis, tailoring treatment to underlying genetic determinants of pharmacological response, monitoring of therapy response, and prognosis. However, the reliability of GEP heavily depends on the input of RNA in sufficient quantity and quality. This highlights the need for standard procedures to ensure best practices for RNA extraction from often small tumor biopsies with variable tissue handling.

Predicting pathological complete response (pCR) after stereotactic ablative radiation therapy (SABR) of lung cancer using quantitative dynamic [F]FDG PET and CT perfusion: a prospective exploratory clinical study.

Background: Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [F]FDG-PET and CT Perfusion (CTP).

Methods: Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study.

Canadian Multicenter Project on Standardization of Programmed Death-Ligand 1 Immunohistochemistry 22C3 Laboratory-Developed Tests for Pembrolizumab Therapy in NSCLC.

Introduction: The programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assay is used to select patients for first or second-line pembrolizumab monotherapy in NSCLC. The PD-L1 IHC 22C3 pharmDx assay requires an Autostainer Link 48 instrument. Laboratories without this stainer have the option to develop a highly accurate 22C3 IHC laboratory-developed test (LDT) on other instruments.

Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

Background: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity.

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

Background: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment.

Methods: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study.

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial.

Importance: Stereotactic ablative radiotherapy (SABR) is a standard treatment option in patients with medically inoperable early-stage non-small cell lung cancer (NSCLC), yet the pathologic complete response (pCR) rate after SABR is unknown. Neoadjuvant SABR in patients with cancer who are fit for resection has been hypothesized to improve local control and induce antitumor immune activity, potentially leading to better outcomes.

Objectives: To determine the pCR rate after SABR and to assess oncologic and toxicity outcomes after a combined approach of neoadjuvant SABR followed by surgery.

Do different sitting postures affect spinal biomechanics of asymptomatic individuals?

Background: Static sitting is thought to be related to low back pain. Of various common seated postures, slouched sitting has been suggested to cause viscoelastic creep. This, in turn, may compromise trunk muscle activity and proprioception, and heightening the risk of low back pain.

Using quantitative tissue phenotype to assess the margins of surgical samples from a pan-Canadian surgery study.

Background: The purpose of this study was to use quantitative tissue phenotype (QTP) to assess the surgical margins to examine if a fluorescence visualization-guided surgical approach produces a shift in the surgical field by sparing normal tissue while catching high-risk tissue.

Methods: Using our QTP to calculate the degree of nuclear chromatin abnormalities, Nuclear Phenotypic Score (NPS), we analyzed 1290 biopsy specimens taken from surgical samples of 248 patients enrolled in the Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer (COOLS) trial. Multiple margin specimens were collected from each surgical specimen according to the presence of fluorescence visualization alterations and the distance to the surgical margins.

Short report: interim safety results for a phase II trial measuring the integration of stereotactic ablative radiotherapy (SABR) plus surgery for early stage non-small cell lung cancer (MISSILE-NSCLC).

Unlabelled: A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR) before surgery improves oncologic outcomes in patients with stage I non-small cell lung cancer (NSCLC). We report a mandated interim safety analysis for the first 10 patients who completed protocol treatment. Operable patients with biopsy-proven T1-2 N0 NSCLC were eligible.

Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case Presentation.

Carcinoid tumour is a well-known primary endobronchial lung neoplasm. Although calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near complete ossification of these tumours is an unusual finding. Such lesions can prove diagnostically challenging at the time of intraoperative frozen section as the latter technique requires thin sectioning of the lesion for microscopic assessment.

Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids.

Feasibility of Targeting PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma.

PIK3CA is the only frequently-mutated, directly druggable oncogene in head and neck squamous cell carcinoma (HNSCC). However, it is unclear if a molecularly-driven intervention trial can be launched successfully, particularly within a single-institution setting secondary to the infrastructure necessary for mutation detection, mutation prevalence, and patient willingness to participate. This study aimed to evaluate 1) local frequency of PIK3CA activating mutations in HNSCC, 2) timeliness of our mutation-profiling clinical pathway, and 3) patients' willingness to enroll in a novel neoadjuvant drug trial.

High frequency of activating PIK3CA mutations in human papillomavirus-positive oropharyngeal cancer.

Importance: Large-scale whole-exome sequencing studies of head and neck squamous cell carcinoma (HNSCC) have established that the disease is dominated by frequent mutations in tumor suppressor genes with rare activating mutations in oncogenes that would be easily targetable with molecular agents. There was evidence in these reports, however, that activating mutations in phosphoinositide 3-kinase catalytic subunit p110α (PIK3CA) were common in patients with human papillomavirus (HPV)-positive tumors. We set out to test this prediction in oropharyngeal patient samples from our institution.