Predictors of residual disease after breast conservation surgery for ductal carcinoma in situ: A retrospective study.

BACKGROUND: Breast-conserving therapy is the standard of care for ductal carcinoma in situ (DCIS). Debate on what constitutes a satisfactory margin persists. This study aimed to identify predictors of residual disease at re-excision. METHODS: This is a population-based retrospective cohort study of women with DCIS who underwent a lumpectomy between 2007 and 2017 in Manitoba, with close (≤2 mm) or positive margins that led to re-excision. RESULTS: The DCIS re-excision rate was 29.3% for 1001 patients. 63.2% of patients were found to have residual disease on re-excision. On univariable analysis, the size, margin status, number of positive margins, type of second surgery, and Van Nuys Prognostic Index score were associated with residual disease on re-excision. The size of DCIS and the number of positive margins remained statistically significant on multivariable analysis. CONCLUSIONS: Re-excision should be rationalized by considering the predictors of residual disease in conjunction with other factors.

Clinical Outcomes in T4 and/or N2 Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: A Retrospective Study.

INTRODUCTION: Total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features. METHODOLOGY: In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with chemoradiotherapy followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019. RESULTS: The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (P = .001) and in the N2 sub-cohort (P = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR. CONCLUSIONS: Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.

Cardiac migration of an implanted hepatic fiducial marker used for stereotactic body radiation therapy - A case report.

ABSTRACT: Stereotactic body radiation therapy (SBRT) has been increasingly used to treat liver malignancies because large doses of radiation can be delivered precisely to the target with a rapid dose falloff. Real-time tracking of implanted fiducial markers (FMs), combined with respiratory gating, further improves the accuracy of treatment delivery and reduces the dose to critical structures. There have been reports of migration of the FMs after implantation for SBRT. Calypso beacons, which use the electromagnetic wave reflections for the image guidance, have recently been used for image-guided liver SBRT. In the literature, there are no reports on the migration of Calypso beacons to the heart after implantation in the liver. In this report, we detail the first case of such migration. Respiratory-gated SBRT guided by the Calypso system was planned for our patient, who developed liver metastases in segments 6 and 5/4B shortly after the completion of radical chemoradiotherapy for anal squamous cell carcinoma. One of the three Calypso beacons inserted in the liver under computed tomography (CT) guidance was found to have migrated to the right ventricle, as seen in CT simulation images. SBRT was delivered with respiratory gating using the remaining two beacons. A fluoroscopic imaging performed during treatment confirmed the migrated marker to the right ventricle. Patient denied any cardiac symptoms and SBRT were delivered uneventfully. Ten months later, the patient died of disease progression.

Total neoadjuvant therapy for rectal cancer: a guide for surgeons.

The modern management of rectal cancers continues to evolve. With the release of data from new landmark randomized controlled trials (RAPIDO, PRODIGE-23), total neoadjuvant therapy (TNT) has moved to the forefront of locally advanced rectal cancer treatment and is considered a standard option in selected patients. Total neoadjuvant therapy promises enhanced systemic disease control, better treatment adherence and less time with an ostomy. However, TNT as currently described encompasses a number of different potential treatment options that differ significantly in terms of their radiation dosage, chemotherapy regimen and order of treatments administered. Being familiar with TNT regimens will be important for rectal cancer surgeons to appropriately advocate for their patients and optimize their outcomes. This article serves as a primer for the general surgeon and offers a pragmatic overview of the indications, realistic expected benefits and potential downsides of each TNT regimen.

Migration of Calypso beacon transponders for hepatic stereotactic body radiotherapy: a report of two cases.

Background: The Calypso 4-dimensional Localization System allows the delivery of high-dose of radiation to a target guided by the implanted transponders. Calypso beacons are used for prostate and liver tumors treated with stereotactic body radiation therapy (SBRT). Several risks associated with this procedure have been previously observed. Here, we report on two cases where Calypso soft tissue transponders migrated to the lung shortly after implantation in liver. Case Description: Two male patients with hepatocellular carcinoma (HCC) underwent insertion of Calypso beacons in liver under image-guidance in preparation for SBRT. Post-procedure images confirmed the presence of the transponders within the liver. However, few days after implant, further imaging revealed a missing marker, in each patient, that had migrated to the right lung. Patients were asymptomatic and SBRT was delivered uneventfully. Conclusions: This is the first report of migration of Calypso beacons from liver to lung. In order to reduce the risk of migration, a Doppler ultrasound (US) prior to insertion could be performed to ensure that the transponders are at a safe distance from blood vessels. Anchored Calypso beacons, currently approved for insertion in the lung, could be tested as a suitable alternative to soft tissue beacons with a lower risk of migration.

Do Sustainable Palliative Single Fraction Radiotherapy Practices Proliferate or Perish 2 Years after a Knowledge Translation Campaign?

In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation (KT) campaign to improve the utilization of single fraction radiotherapy (SFRT) over multiple fraction radiotherapy (MFRT) for palliative management of bone metastases. The campaign significantly increased short-term SFRT utilization. We assess the time-dependent effects of KT-derived SFRT utilization 12-24 months removed from the KT campaign in a Provincial Cancer Program. This study identified patients receiving palliative radiotherapy for bone metastases in Manitoba in the 2018 calendar year using the provincial radiotherapy database. The proportion of patients treated with SFRT in 2018 was compared to 2017. Logistic regression analyses identified risk factors associated with MFRT receipt. In 2018, 1008 patients received palliative radiotherapy for bone metastasis, of which 63.3% received SFRT, a small overall increase in SFRT use over 2017 (59.1%). However, 41.1% of ROs demonstrated year-over-year decreases in SFRT utilization, indicative of a time-dependent loss of SFRT prescription habits derived from KT. Although SFRT use increased slightly overall in 2018, evidence of compliance fatigue was observed, suggestive of a time-perishing property of RO prescription behaviours derived from KT methodologies. Verification of the study's findings in larger cohorts would be beneficial. These findings highlight the need for additional longitudinal KT reinforcement practices in the years following KT campaigns.

Evaluation of the ITV-margin and variables affecting bladder and mesorectal deformation during long course neoadjuvant radiotherapy for rectal cancer.

Internal target volume (ITV) margins were estimated by evaluating the movement of mesorectum and bladder during neoadjuvant long-course radiation therapy (RT) for rectal cancer. In this prospective study, 23 patients with rectal cancer had planning CT (pCT) and weekly cone beam CT (CBCT) in supine position during preoperative long-course RT. Mesorectal wall motion was analyzed based on the coordinates of the most anterior, posterior, left and right points on the pCT and CBCT. Overlap volume (OV) between the pCT bladder and CBCT mesorectum was generated. Variables that might affect relative bladder volume (ratio of CBCT to pCT bladder volumes), anterior mesorectal wall position, and OV were studied. ITV margins were also calculated. In females, smaller OV and less movement of the upper anterior mesorectal wall were identified, suggesting smaller ITV margins might be required compared to males. The relative bladder volume did not change significantly over time and was correlated with OV: the larger the relative bladder volume, the less the OV. ITV margin of 0.8 to 1.1 cm in right-left direction is satisfactory. Posteriorly, only 8 to 9 mm margin is required for upper and mid rectal regions but double of this is required for inferior third. Anteriorly, 1.3 cm margin is adequate for lower and mid rectal regions and 2.4 cm is required superiorly. An anisotropic ITV expansion of clinical target volume (CTV) for rectal cancer radiotherapy contouring provides a robust method to encompass the deformation of bladder and mesorectum. The ITV margin should take into account sex and distance from the anal verge.

Do Coordinated Knowledge Translation Campaigns Persuade Radiation Oncologists to Use Single-Fraction Radiation Therapy Compared With Multiple-Fraction Radiation Therapy for Bone Metastases?

PURPOSE: Although level 1 evidence supports the use of single-fraction radiation therapy (SFRT) compared with multiple-fraction radiation therapy (MFRT) for the palliative management of bone metastases, SFRT is underused. In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation campaign in Manitoba, Canada featuring educational outreach visits, local consensus meetings, and audit and feedback interventions to encourage greater use of SFRT. This study assessed the impact of this campaign on SFRT use and identified variables associated with MFRT usage. METHODS AND MATERIALS: This retrospective, population-based cohort study identified all patients treated with palliative radiation therapy for bone metastases in Manitoba, Canada, from January 1, 2017, to December 31, 2017, using the provincial radiation therapy database. Baseline characteristics were extracted and tabulated by fractionation schedule. The proportion of patients treated with SFRT in 2017 (postintervention) was compared with the 2016 (preintervention) levels. Univariable and multivariable logistic regression analyses were performed to identify risk factors associated with MFRT use. RESULTS: In 2017, 927 patients received palliative radiation therapy for bone metastasis, of which 548 (59.1%) received SFRT, a 21.1% absolute increase in SFRT use compared with 2016 levels (38.0%). With use of multivariable analysis, variables associated with receipt of MFRT included: complicated bone metastasis, soft tissue extension, hematological primary malignancy, and treatment at a subsidiary center. CONCLUSION: The comprehensive knowledge translation campaign carried out in Manitoba resulted in a significant increase in SFRT use for bone metastases. Continued audit/feedback strategies are recommended to further reinforce knowledge translation efforts supporting SFRT use in the future.

Epidemiology, clinical treatment patterns, and survival of hepatocellular carcinoma in Manitoba.

Background: Hepatocellular carcinoma (HCC) has a very poor survival rate, especially for those who do not receive a potentially curative therapy. Methods: Treatment details were collected for 320 HCC patients diagnosed in Manitoba between January 2011 and December 2015. Patients had a mean age of 67.3 years, and 71.6% were men. Of these patients, 67 (20.9%) received curative treatment, 36 (11.3%) received non-curative treatment, and 217 (67.8%) received supportive care only; 71.3% of patients had liver cirrhosis. Alcoholic cirrhosis was the most common etiology of chronic liver disease (22.2%). Results: Those who received curative treatment had a significantly lower incidence of portal vein thrombosis and multinodular disease than those in other groups. Patients who received supportive care only had a higher incidence of ascites. We found no difference in the distribution of cirrhosis or portal hypertension among the treatment groups. The 2- and 5-year overall survival rates for the whole cohort were 27% and 14%, respectively. No significant change was found in 2-year survival for patients diagnosed in each year from 2011 to 2015 (p = 0.250). Also, we found no significant change in proportion of treatment given to patients over the same period (p = 0.432). Conclusion: The poor survival rate of HCC patients in Manitoba could potentially be improved by maximizing the use of local therapy and by implementing multidisciplinary-based case discussion. Efforts should also be directed toward early management of infective, alcoholic, and non-alcoholic steatohepatitis, which will, we hope, lead to a reduction in the incidence of HCC.

Predictors of Residual Disease After Breast Conservation Surgery.

INTRODUCTION: Breast-conserving therapy is the standard of care for early-stage breast cancer. In the era of multimodality therapy, the debate on the value of revision surgery for compromised margins continues, and high re-excision rates persist despite updated guidelines. Our study sought to identify the local re-excision rate for compromised margins after lumpectomy, and identify predictors of residual disease at re-excision. METHODS: This population-based retrospective cohort study included women with breast cancer who underwent a lumpectomy between 2009 and 2012 in Manitoba, with close (≤ 2 mm) or positive margins that led to re-excision. Patient demographics and tumor characteristics were identified through provincial cancer registries and chart reviews. For patients with invasive cancer, the six anatomical margins were reported for margin status, width, and pathology type at the margin. RESULTS: Of the 2494 patients identified, 556 women underwent re-excision, yielding a re-excision rate of 22.29%. Of our 311 patients with invasive cancer who underwent re-excision, 62.7% had residual disease identified on revision. On univariable analysis, the size and grade of the invasive component, nodal stage, and the number of positive margins were associated with residual disease on re-excision (p < 0.05). With the exception of nodal stage, the same variables remained statistically significant on multivariable analysis. CONCLUSIONS: Our results suggest that even in the absence of 'no ink on tumor', the cancer size and grade in lumpectomy specimens are high-risk factors for residual disease, and this subgroup of patients may benefit from re-excision. Long-term follow-up of this cohort is required to determine their risk of recurrence after adjuvant treatment.

Clinical Implementation of a Model-Based In Vivo Dose Verification System for Stereotactic Body Radiation Therapy-Volumetric Modulated Arc Therapy Treatments Using the Electronic Portal Imaging Device.

PURPOSE: To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically. METHODS AND MATERIALS: From December 2013 to July 2016, 117 stereotactic body radiation therapy-volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in June 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB-predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors. RESULTS: The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively. CONCLUSIONS: Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors.

Wait Time from Suspicion to Surgery for Breast Cancer in Manitoba.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women. The pathway for its diagnosis and treatment is relatively standardized. Nevertheless, there can be significant delays affecting the journey. The aim of this retrospective study is to describe the BC wait times (WT) from suspicion to first surgery in Manitoba and to examine factors associated with WT variability. METHODS: The cohort is composed of patients with stages I-III breast cancer who were diagnosed between September 1, 2009, and August 31, 2010, and referred to a cancer center. Patients' journeys were tracked and divided into three sequential intervals from suspicion to first diagnostic test, from first diagnostic test to diagnosis and from diagnosis to first surgery. RESULTS: Four hundred and four patients were included of whom 134 presented through the screening program. There was no difference between the study cohort and population data from the provincial Cancer Registry concerning the distribution of age, stage of cancer or residence. The median WT from suspicion to surgery was 78 days. In the screen-detected group (SD), a difference in median WT from suspicion to first diagnostic test was found for distance. This finding was first to test location, where those who travel less had longer WT than those who have longer journeys. Patients who went to centers that offer both imaging and biopsy services, even if the required test is imaging only, had to wait longer than those who went to centers that provide imaging only. SD patients needing more than one diagnostic test had a longer WT from the first test to pathological diagnosis if the first test did not include a biopsy. Patients who were seen by surgeons before final pathological diagnosis had a shorter WT from diagnosis to first surgery than those who had the surgical consult after tissue diagnosis was made. A delay to surgery was observed in the whole cohort if a plastic surgeon is required in addition to the surgical oncologist and the non-screen detected group if a radiologist is necessary. CONCLUSIONS: Variability in WT from suspicion to surgical management was found between various BC patient groups and between diagnostic centers with different types of services. The order of the provided diagnostic and surgical services may have contributed to WT. Addressing this variability by restructuring the care pathway and improving communication between different disciplines, has the potential to reduce WT.