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Thymic epithelial tumors are presently staged using a consistent TNM classification developed by the International Association for the Study of Lung Cancer (IASLC) and approved by the Union for International Cancer Control and the American Joint Committee on Cancer. The stage classification is incorporated in the eight edition of the TNM classification of thoracic malignancies. The IASLC Staging and Prognostic Factors Committee (SPFC)-Thymic Domain (TD) is in charge for the next (ninth) edition expected in 2024. The present article represents the midterm report of the SPFC-TD: in particular, it describes the unresolved issues identified by the group in the current stage classification which are worth being addressed and discussed for the ninth edition of the TNM classification on the basis of the available data collected in the central thymic database which will be managed and analyzed by Cancer Research And Biostatistics. These issues are grouped into issues of general importance and those specifically related to T, N, and M categories. Each issue is described in reference to the most recent reports on the subject, and the priority assigned by the IASLC SPFC-TD for the discussion of the ninth edition is provided.

Uncontrolled studies suggest that the addition of high dose rate intraluminal brachytherapy (HDRIB) to external beam radiotherapy (EBR) may improve palliation for patients with advanced non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the potential clinical benefit of adding HDRIB to EBR in a multicenter randomized trial.Patients with symptomatic stage III or IV NSCLC with endobronchial disease were randomized to EBR (20Gy in 5 daily fractions or 30Gy in 10 daily fractions) or the same EBR+HDRIB (14Gy in 2 fractions over two weeks). The primary outcome was the proportion of patients who achieved symptomatic improvement in patient-reported overall lung cancer symptoms on the Lung Cancer Symptom Scale (LCSS) at 6 weeks following randomization. Secondary outcomes included improvement in individual symptoms, symptom progression free survival, overall survival and toxicity. The planned sample size was 250 patients based on detection of symptomatic improvement from 40 to 60% with a two-sided α of 0.05 and 80% power.134 patients were randomized over 4.5 years: 67 to each arm. The study closed early due to slow accrual. The mean age was 69.8 years, and 67% had metastatic disease. At six weeks 19 patients (28.4%) in the EBR arm and 20 patients (29.9%) in the EBR+HDRIB arm experienced an improvement in lung cancer symptoms (p=0.84). When limited to patients who completed the LCSS percentages were 40.4% vs 47.6%, respectively, p=0.49. Between group differences in mean change scores (0.3-0.5 standard deviations) in favor of EBR+HDRIB were observed for overall symptoms, but only hemoptysis was significantly improved (p=0.03). No significant differences were observed in progression free or overall survival. Grade 3/4 toxicity was similar between groups.Small to moderate improvements were seen in symptom relief with the combined therapy, but they did not reach statistical significance. Further research is necessary before recommending HDRIB in addition to EBR for palliation of lung cancer symptoms.

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. Results: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobespecific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for RO, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between RO and R(un) in pN0 cases. Conclusions: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

To evaluate a novel navigation system for breast brachytherapy, based on ultrasound (US)-guided catheter needle implantations followed by electromagnetic (EM) tracking of catheter paths. Breast phantoms were produced, containing US–visible tumors. Ultrasound was used to localize the tumor pose and volume within the phantom, followed by planning an optimal catheter pattern through the tumor using navigation software. An electromagnetic (EM)-tracked catheter needle was used to insert the catheters in the desired pattern. The inserted catheters were visualized on a post-implant CT, serving as ground truth. Electromagnetic (EM) tracking and reconstruction of the inserted catheter paths were performed by pulling a flexible EM guidewire through each catheter, performed in two clinical brachytherapy suites. The accuracy of EM catheter tracking was evaluated by calculating the Hausdorff distance between the EM-tracked and CT-based catheter paths. The accuracy and clinical feasibility of EM catheter tracking were also evaluated in three breast cancer patients, performed in a separate experiment room. A total of 71 catheter needles were implanted into 12 phantoms using US guidance and EM navigation, in an average ± SD time of 8.1 ± 2.9 min. The accuracy of EM catheter tracking was dependent on the brachytherapy suite: 2.0 ± 1.2 mm in suite 1 and 0.6 ± 0.2 mm in suite 2. EM catheter tracking was successfully performed in three breast brachytherapy patients. Catheter tracking typically took less than 5 min and had an average accuracy of 1.7 ± 0.3 mm. Our preliminary results show a potential role for US guidance and EM needle navigation for implantation of catheters for breast brachytherapy. EM catheter tracking can accurately assess the implant geometry in breast brachytherapy patients. This methodology has the potential to evaluate catheter positions directly after the implantation and during the several fractions of the treatment.

Objectives The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee-Thymic Domain conducted a web-based cross-sectional survey to assess the acceptance of the TNM thymic staging system in the thoracic community. Methods A 50-item, web-based questionnaire was circulated among the members of the major thymic organizations worldwide from September to December 2018. The survey consisted of six sections (general information; overall perception of the TNM system; pretreatment staging; T category; N category; and perioperative treatments). Results In total, 217 responses were collected from 37 countries in four continents. The TNM classification was considered useful by 78% of the responders (N = 169); the Masaoka-Koga staging system was being used by 87% of the responders (N = 189). With regard to the T category, most responders (mostly surgeons) felt that the capsular and mediastinal pleural involvements should be considered separate T categories. As for the N category, 48% of the responders (N = 105) used the International Thymic Malignancies Interest Group/International Association for the Study of Lung Cancer thymic nodal map, and lymph node dissection (N1/N2) was performed for 50%/21% thymomas and 66%/41% thymic carcinomas. While analyzing the results by the three continents (Europe, Asia, and Americas), responders in Asia were found to report the largest use of the TNM system, the greatest attention to the N category, and the best participation in international thymic databases. Conclusions The survey indicates that the Union for International Cancer Control/American Joint Committee on Cancer TNM stage classification of thymic tumors is gaining acceptance among the scientific community. The present results will guide the work of the Staging and Prognostic Factors Committee-Thymic Domain for the revision of the ninth edition of the TNM stage classification of thymic tumors.

Mediastinal lesions are uncommon; studies on their distribution are, in general, small and from a single institution. Furthermore, these studies are usually based on pathology or surgical databases and, therefore, miss many lesions that did not undergo biopsy or resection. Our aim was to identify the distribution of lesions in the mediastinum in a large international, multi-institutional cohort.At each participating institution, a standardized retrospective radiology database search was performed for interpretations of computed tomography, positron emission tomography-computed tomography, and magnetic resonance imaging scans including any of the following terms: "mediastinal nodule," "mediastinal lesion," "mediastinal mass," or "mediastinal abnormality" (2011-2014). Standardized data were collected. Statistical analysis was performed.Among 3308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%), and lymphomas (16.1%) were most common. The distribution of lesions varied among mediastinal compartments; thymomas (38.3%), benign cysts (16.8%), and neurogenic tumors (53.9%) were the most common lesions in the prevascular, visceral, and paravertebral mediastinum, respectively (p0.001). Mediastinal compartment was associated with age; patients with paravertebral lesions were the youngest (p0.0001). Mediastinal lesions differed by continent or country, with benign cysts being the most common mediastinal lesions in the People's Republic of China, thymomas in Europe, and lymphomas in North America and Israel (p0.001). Benign cysts, thymic carcinomas, and metastases were more often seen in larger hospitals, whereas lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p 0.01).Our study confirmed that the spectrum and frequency of mediastinal lesions depend on mediastinal compartment and age. This information provides helpful demographic data and is important when considering the differential diagnosis of a mediastinal lesion.

Introduction Patients with lung cancer who harbor multiple pulmonary sites of disease have been challenging to classify; a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee was charged with developing proposals for the eighth edition of the tumor, node, and metastasis (TNM) classification to address this issue. Methods A systematic literature review and analysis of the International Association for the Study of Lung Cancer database was performed to develop proposals for revision in an iterative process involving multispecialty international input and review. Results Details of the evidence base are summarized in other articles. Four patterns of disease are recognized; the clinical presentation, pathologic correlates, and biologic behavior of these suggest specific applications of the TNM classification rules. First, it is proposed that second primary lung cancers be designated with a T, N, and M category for each tumor. Second, tumors with a separate tumor nodule of the same histologic type (either suspected or proved) should be classified according to the location of the separate nodule relative to the index tumor—T3 for a same-lobe, T4 for a same-side (different lobe), and M1a for an other-side location—with a single N and M category. Third, multiple tumors with prominent ground glass (imaging) or lepidic (histologic) features should be designated by the T category of the highest T lesion, the number or m in parentheses (#/m) to indicate the multiplicity, and a collective N and M category for all. Finally, it is proposed that diffuse pneumonic-type lung cancers be designated by size (or T3) if in one lobe, T4 if involving multiple same-side lobes, and M1a if involving both lungs with a single N and M category for all areas of involvement. Conclusion We propose to tailor TNM classification of multiple pulmonary sites of lung cancer to reflect the unique aspects of four different patterns of presentation. We hope that this will lead to more consistent classification and clarity in communication and facilitate further research in the nature and optimal treatment of these entities.

41 Background: Provider experience and physician burnout has been recognized as a critical issue in medicine. Ontario, Canada has a single payer cancer system run by Ontario Health (Cancer Care Ontario) with a mandate covering system level planning and delivery of cancer services, funding, and quality improvement. As part of a larger provincial initiative to address clinician burnout, we examined the prevalence and drivers of burnout in practicing physician oncologists in Ontario. Methods: In November-December 2019, surgical, medical, hematological, and radiation oncologists in Ontario were invited to complete an anonymous online survey to assess burnout and its drivers. Burnout prevalence was assessed through the Maslach Burnout Inventory – Human Services Survey for Medical Personnel (MBI-HSS MP). Data on demographic, workplace, engagement, and practice profiles were collected. Logistic regression modeling was conducted to assess key variables associated with “high” burnout using a common definition of high scores on the MBI subscales of emotional exhaustion (EE) (> 27) and/or depersonalization (DP) (>10). Results: Response rate to the survey was 44% (n=418) with 72% reporting high levels of burnout. Mean scores for EE (30.7, SD 12.1) and DP (9.9, SD 6.7) were consistent with high burnout. Participants endorsed known drivers of burnout including: 1) a poor culture of wellness at work (e.g., not comfortable talking to leadership (72%), 2) inefficiencies of practice (e.g. feeling insufficient documentation time (67%)) and 3) personal resilience (e.g. not feeling they are contributing professionally in ways they value (21%)). Age (

PURPOSE: Timely lung cancer care has been associated with improved clinical outcomes and patient satisfaction. We identified improvement opportunities in lung cancer management pathways at Kingston Health Sciences Centre. Quality improvement strategies led to the implementation of a multidisciplinary lung cancer clinic (MDC). METHODS: We set an outcome measure of decreasing the time from diagnosis to first cancer treatment by 10 days within 6 months of clinic implementation. We implemented a weekly MDC that involved respirologists, medical oncologists, and radiation oncologists at which patients with new lung cancer diagnoses were offered concurrent oncology consultation. We used Plan-Do-Study-Act cycles to guide our improvement initiatives. A total of five Plan-Do-Study-Act cycles spanned 14 months and consisted of an MDC pilot clinic, large-scale MDC launching, debriefing meetings, and clinic expansion. Pre-MDC data were analyzed retrospectively to establish baseline and prospectively for improvement. Statistical Process Control XmR(i) charts were used to report data. RESULTS: Since MDC initiation, 128 patients have been seen in 34 MDC clinics (3.8 patients per clinic). Mean days from diagnosis to first oncology assessment decreased from 12.4 days to 3.9 days, and mean days from diagnosis to first cancer treatment decreased from 39.5 to 15.0 days, both of which demonstrated special cause variation. Time to assessment and treatment improved for patients with every stage of lung cancer and for both small-cell and non–small-cell subtypes. CONCLUSION: MDC shortens the time from lung cancer diagnosis to oncology assessment and treatment. Time to treatment improved more than time to oncology assessment, which suggests the improvement is related to benefits beyond faster oncology assessment.

Optimal regional management in breast cancer patients has yet to be established. In patients who are clinically node-negative, but sentinel lymph node biopsy (SLNB)-positive, the treatment paradigm has shifted toward the de-escalation of further axillary management. In patients with 2 or fewer positive sentinel nodes, the standard of practice has shifted away from complete axillary lymph node dissection (ALND) as a result of the ACOSOG Z0011 trial. The role of regional nodal irradiation (RNI) to the axilla, supraclavicular and internal mammary regions has also been investigated in the setting of positive SLNB in trials such as the MA20 and EORTC 22922. Having shown evidence of benefit in locoregional control, efforts are now focused on comparing ALND with RNI in patients with limited nodal disease. Results of early trials such as AMAROS suggest noninferiority of radiotherapy. In patients with node-positive or locally advanced disease, neoadjuvant chemotherapy (NAC) is often used to downsize or downstage the disease. The utility of SLNB after NAC has been investigated, with discordant results reported from a number of trials. Current trials in progress seek to validate the noninferiority of RNI compared with ALND in patients with limited nodal disease, or in some trials, the complete omission of further axillary management. There is a global paradigm shift toward de-escalation of axillary management on the basis of recent evidence suggesting lack of benefit from overaggressive treatment. In this review we aim to summarize the seminal trials addressing regional management in breast cancer to illustrate this fact.

Background Delays in the management of lung cancer (LC) are associated with inferior outcomes. Multidisciplinary cancer clinics (MDCC) can improve timeliness and quality of care. Objectives Decrease time from LC diagnosis to oncology assessment from 13 to 3 days, and to treatment from 30 to Methods We implemented a weekly MDCC, involving Respirologists, Medical Oncologists (MO) and Radiation Oncologists (RO), where patients with new LC diagnoses received concurrent oncology consultation. We retrospectively analysed data pre-MDCC (November 2016 – February 2017) and prospectively for improvements (February – July 2017). Improvement cycles included MDCC clinic launching and a debriefing/troubleshooting meeting. Data are reported as n(%), and means as per Statistical Process Control XmR(i) charts. Results 117 patients (44 pre-MDCC, 73 post-MDCC) were analysed. Most patients had stage 4 (44, 37.6%) or stage 1 LC (32, 27%). All patients saw Respirology, in addition to MO (85, 72.6%), RO (113, 96.6%), or both (83, 71.0%). The proportion of treated patients was unchanged pre- vs. post-MDCC (88.6%, 85.4%). Mean days from diagnosis to oncology assessment decreased from 14.3 to 5.0 days. Time from diagnosis to first treatment decreased from 39.8 to 27.2 days after the first improvement cycle, and to 18.1 days after the second improvement cycle (Figure 1), with less variation in time to treatment after improvement events. Conclusions MDCC shortens time from LC diagnosis to oncology assessment and treatment. Time to treatment improved more than time to oncology assessment, suggesting the improvement is likely related to benefits beyond just faster oncology assessment.

INTRODUCTION: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons.METHODS: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases.RESULTS: The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage.CONCLUSIONS: The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts.

Twenty dialysis and renal transplant patients with parathyroid hyperplasia underwent a total parathyroidectomy and an autotransplantation in forearm muscle. Twelve patients were available for investigation of the function of the transplanted parathyroid tissue. Differential studies of the two arms revealed functioning of the transplanted tissue in all cases. This was more readily demonstrated by determining the intact honnone in both arms.

For this guideline, we investigated the effectiveness of radiotherapy with curative intent in medically inoperable patients with early-stage non-small-cell lung cancer (nsclc). The guideline was developed by Cancer Care Ontario&rsquo, s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of mainly retrospective studies, expert consensus, and formal internal and external reviews. &#9632, Stereotactic body radiation therapy (sbrt) with curative intent is an option that should be considered for patients with early-stage, node-negative, medically inoperable nsclc. Qualifying Statements &#9632, Because of the high dose per fraction, the planning process and treatment delivery for sbrt require the use of advanced technology to maintain an appropriate level of safety. Consistent patient positioning and 4-dimensional analysis of tumour and critical structure motion during simulation and treatment delivery are essential. &#9632, Preliminary results for proton-beam therapy have been promising, but the technique requires further clinical study. &#9632, Recommended fractionation schemes for sbrt should result in a biologically effective dose of 100 or greater by the linear quadric model, choosing an &alpha, /&beta, value of 10 [bed10(LQ) &ge, 100]. Qualifying Statements &#9632, Because of the increased risk of treatment-related adverse events associated with centrally located tumours, consideration of tumour size and proximity to critical central structures is required when determining the dose and fractionation. &#9632, Examples of dose&ndash, fractionation schemes used in the included studies have been provided. &#9632, Based on the current evidence and the opinion of the authors, radiation doses at bed10(LQ) greater than 146 might significantly increase toxicity and should be avoided. &#9632, Determination of the radiation bed by the linear quadratic model has limitations for the extreme hypofractionated schemes used in sbrt.

The analyses of the retrospective database of the International Association for the Study of Lung Cancer (IASLC), consisting of more than 81,000 evaluable patients diagnosed with lung cancer between 1990 and 2000, formed the basis of recommendations to the Union for International Cancer Control and the American Joint Committee on Cancer for the revision of the sixth edition of the tumor, node, and metastasis (TNM) classification of lung cancer. However, despite the large number of patients, not all descriptors could be validated. This prompted a new collection of retrospective and prospective data to overcome the limitations of the original retrospective database. The new IASLC database has information on 94,708 new patients diagnosed of lung cancer between 1999 and 2010. They originated from 35 sources in 16 countries, and 4,667 were submitted via the online electronic data capture system. Europe contributed 46,560 patients, Asia: 41,705, North America: 4,660, Australia: 1,593, and South America: 190. After exclusions, 77,156 (70,967 with nonsmall cell lung cancer and 6,189 with small cell lung cancer) remained for analysis. This database will be analyzed according to established objectives for the T, the N, and the M components to inform the eighth edition of the TNM classification of lung cancer due to be published in 2016. The IASLC hopes for the continuing contribution of our partners around the world to improve the classification of anatomical extent of disease, but also to create prognostic groups in a parallel project of the IASLC Staging and Prognostic Factors Committee.

Purpose To determine the current use of brachytherapy, characteristics of the brachytherapy workforce, and barriers to development and maintenance of brachytherapy programs across Canada. Methods and Materials A survey was designed to inquire about the use of brachytherapy and was sent to all Canadian radiation oncologists. Results Of the 116 respondents, we identified 80 radiation oncologists from 33 of 41 responding centers who currently or in the past have practiced brachytherapy. Responses were received from 30% overall and 80% of provinces. Approximately 58% of the respondents treat in one site with brachytherapy, whereas 12% treat in three or more sites. Gynecologic (GYN) and genitourinary are the most commonly treated sites (49% of respondents). For all sites, there was a large range in the number of patients treated with brachytherapy by each radiation oncologist per year (i.e., cervix: 1–50). Approximately 49% of the respondents have discontinued practicing brachytherapy for a certain site, most commonly head and neck (28%), GYN (25%), and bronchus (24%). The most common reasons include reassignment or lack of a local program. The most common reasons why brachytherapy is not used for sites other than GYN and prostate include lack of infrastructure and insufficient training of radiation oncologists rather than insufficient patient numbers or lack of evidence for a benefit of brachytherapy. Conclusions Within its limitations, our study suggests a mismatch between demand and availability of brachytherapy programs across Canada. In light of finite resources, a rational approach to investment in brachytherapy is needed and this must be based on a formal audit of brachytherapy demand and use.

Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma.Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis.There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p0.0001).A recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2.

Introduction: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM. Methods: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical MO (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases. Results: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggest a possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1). Conclusions: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Patients with early-stage non-small-cell lung cancer (NSCLC) who are unable to undergo surgery can be offered radiation therapy (RT). Previously, conventional RT was offered; however, newer techniques such as stereotactic body RT (SBRT) have become available. The objective of the present systematic review was to investigate the effectiveness of RT with curative intent in patients with early-stage medically inoperable NSCLC. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing stereotactic RT with curative intent compared with observation or other types of RT for early-stage, medically inoperable, NSCLC. Comparisons of radiation dosing or fractionation schedules for SBRT were included. We include 4 systematic reviews and 52 observational studies. The evidence suggests that SBRT compared with observation or other forms of RT, such as accelerated hypofractionated RT, 3-dimensional conformal RT, conventional fractionated RT, external beam RT, proton beam therapy, and carbon ion therapy, could have similar or improved results in survival or local control, with similar or fewer adverse effects. Evidence also suggests that local tumor control and survival were associated with the biologically effective dose (BED) for SBRT. Several studies suggested a cutoff of approximately 100 BED correlated significantly with patient outcomes. The presented evidence suggests that SBRT compared with other forms of RT is a reasonable treatment option for patients with medically inoperable early-stage NSCLC.

Introduction Stage classification provides a consistent language to describe the anatomic extent of disease and is therefore a critical tool in caring for patients. The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer developed proposals for revision of the classification of lung cancer for the eighth edition of the tumor, node, and metastasis (TNM) classification, which takes effect in 2017. Methods An international database of 94,708 patients with lung cancer diagnosed in 1999–2010 was assembled. This article describes the process and statistical methods used to refine the lung cancer stage classification. Results Extensive analysis allowed definition of tumor, node, and metastasis categories and stage groupings that demonstrated consistent discrimination overall and within multiple different patient cohorts (e.g., clinical or pathologic stage, R0 or R-any resection status, geographic region). Additional analyses provided evidence of applicability over time, across a spectrum of geographic regions, histologic types, evaluative approaches, and follow-up intervals. Conclusions An extensive analysis has produced stage classification proposals for lung cancer with a robust degree of discriminatory consistency and general applicability. Nevertheless, external validation is encouraged to identify areas of strength and weakness; a sound validation should have discriminatory ability and be based on an independent data set of adequate size and sufficient follow-up with enough patients for each subgroup.

Purpose To describe the outcomes of peer review across all 14 cancer centers in Ontario. Methods and Materials We identified all peer-reviewed, curative treatment plans delivered in Ontario within a 3-month study period from 2013 to 2014 using a provincial cancer treatment database and collected additional data on the peer-review outcomes. Results Considerable variation was found in the proportion of peer-reviewed plans across the centers (average 70.2%, range 40.8%-99.2%). During the study period, 5561 curative plans underwent peer review. Of those, 184 plans (3.3%) had changes recommended. Of the 184 plans, the changes were major (defined as requiring repeat planning or having a major effect on planning or clinical outcomes, or both) in 40.2% and minor in 47.8%. For the remaining 12.0%, data were missing. The proportions of recommended changes varied among disease sites (0.0%-7.0%). The disease sites with the most recommended changes to treatment plans after peer review and with the greatest potential for benefit were the esophagus (7.0%), uterus (6.7%), upper limb (6.3%), cervix and lower limb (both 6.0%), head and neck and bilateral lung (both 5.9%), right supraclavicular lymph nodes (5.7%), rectum (5.3%), and spine (5.0%). Although the heart is an organ at risk in left-sided breast treatment plans, the proportions of recommended changes did not significantly differ between the left breast treatment plans (3.0%, 95% confidence interval 2.0%-4.5%) and right breast treatment plans (2.4%, 95% confidence interval 1.5%-3.8%). The recommended changes were more frequently made when peer review occurred before radiation therapy (3.8%) than during treatment (1.4%-2.8%; P =.0048). The proportion of plans with recommended changes was not significantly associated with patient volume ( P =.23), peer-review performance ( P =.36), or center academic status ( P =.75). Conclusions Peer review of treatment plans directly affects the quality of care by identifying important clinical and planning changes. Provincial strategies are underway to optimize its conduct in radiation oncology.

The aim of this overview was to assess the utility of various imaging technologies (fluoroscopy, ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography) for the treatment planning of high dose rate brachytherapy for cervical cancer. Reviews and primary studies comparing different imaging technologies used during high dose rate brachytherapy for cervical cancer and published from 1988 to 2008 were sought by searching MEDLINE and EMBASE databases, the Cochrane Library, personal files and reference lists of identified studies, and by contacting experts. Study selection, study quality assessment and data extraction were carried out in duplicate. Twelve studies met the inclusion criteria. No systematic reviews or randomised controlled studies (RCTs) were located. The validity assessment revealed that the quality of the existing studies is very variable. This is the first systematic review in the area of imaging technologies for cervix brachytherapy. No RCTs have been located and it is possible that an RCT is not the optimal methodology to assess imaging technologies. However, in this area there is a need for more prospective studies and for studies that consider the expertise of the operators in their design. The studies found supported the use of three-dimensional imaging as opposed to the traditional two-dimensional imaging. However, apart from the effectiveness of visualising tumours and surrounding tissues, the utility of imaging technologies in clinical practice is determined by other contextual factors, such as their availability, accessibility and ease of use.

Aims Brachytherapy is a standard therapy for cervical cancer; it allows for the delivery of a high dose of radiation to the tumour while sparing the surrounding healthy tissues. With this document, the Brachytherapy Cervical Cancer Expert Working Group (BCCEWG) aimed to provide advice on organisational and technical aspects of the delivery of brachytherapy services in Ontario, Canada. Materials and methods We sought technical documents, practice guidelines and standards through an environmental scan of internet resources, an iterative search of the literature on MEDLINE and EMBASE, and a search of reference lists of included documents. Results We identified 20 guidance documents authored by 10 organisations; 11 documents were identified through the environmental scan, five through the literature search and four from reference lists. The recommendations included in this document were developed by the BCCEWG through the selection and review of the evidence and informal consensus. Conclusions These organisational recommendations aim to set the stage for high-quality delivery of brachytherapy for cervical cancer services in the province of Ontario, Canada. They address the characteristics of the practice setting, including facilities, equipment, delivery suite, imaging technologies, treatment planning and dosimetry; the practice team, including team members, roles, training, team caseload/volumes and qualifications; and the quality assurance domain, including documentation, audit, safety and quality control.

This review summarizes recent updates on the role and timing of radiotherapy (RT). Multidisciplinary case discussion and careful case selection before any treatment modality can avoid morbidity and mortality. Advances in RT technology include proton treatment, respiratory gating, immobilization, forward planning, intensity-modulated radiation (IMRT), volumetric-modulated arc therapy (VMAT), tomotherapy, image-guided radiation treatment (IGRT) and on-treatment cone-beam computerized axial tomography scan (CBCT). These allow decreased doses to organ at risk such as brachial plexus, ribs, spinal cord, contralateral esophagus (CE), lung, heart, and adjacent liver. We used mesothelioma and thymoma as an example to illustrate improvements in RT techniques in past decade.

Introduction It can be difficult to distinguish between a second primary and a metastasis in patients with lung cancer who have more than one pulmonary site of cancer. Methods A systematic review of the literature was conducted by a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee to develop recommendations to identify second primary lung cancers. The process entailed review of knowledge relating to the mechanism of metastasis, determination of clonality, and outcomes of patients with resected tumors. Results It is easier to determine that two tumors are different than that they are the same; finding similarities does not establish that they are the same. For example, most second primary lung cancers are of the same histotype. Few criteria are reliable by themselves; these include different histologic cancer types or matching DNA breakpoints by sequencing and a comprehensive histologic assessment of resected specimens. Characteristics that are suggestive but associated with potential misclassification include the presence or absence of biomarkers, imaging characteristics, and the presence or absence of nodal involvement. Conclusions Clinical and pathologic (i.e., after resection) criteria are presented to identify two foci as separate primary lung cancers versus a metastasis. Few features are definitive; many commonly used characteristics are suggestive but associated with a substantial rate of misclassification. Careful review by a multidisciplinary tumor board, considering all available information, is recommended.

The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition.

For nearly 40 years, there was no generally accepted staging system for malignant pleural mesothelioma. In 1994, members of the International Mesothelioma Interest Group, in collaboration with the International Association for the Study of Lung Cancer, proposed a TNM staging system based on analyses of outcomes in retrospective surgical series and small clinical trials. Subsequently accepted by the American Joint Commission on Cancer and the Union for International Cancer Control for the sixth editions of their staging manuals, this system has since been the international staging standard. However, it has significant limitations, particularly with respect to clinical staging and to the categories for lymph node staging. Here we provide an overview of the development of the International Association for the Study of Lung Cancer malignant pleural mesothelioma staging database, which was designed to address these limitations through the development of a large international data set. Analyses of this database, described in papers linked to this overview, are being used to inform revisions in the eighth editions of the American Joint Commission on Cancer and Union for International Cancer Control staging systems. ispartof: Journal of Thoracic Oncology vol:11 issue:12 pages:2082-2088 ispartof: location:United States status: published

Introduction Small cell lung cancer (SCLC) is commonly classified as either limited or extensive, but the Union for International Cancer Control TNM Classification of Malignant Tumours seventh edition (2009) recommended tumor, node, and metastasis (TNM) staging based on analysis of the International Association for the Study of Lung Cancer (IASLC) database. Methods Survival analyses were performed for clinically and pathologically staged patients presenting with SCLC from 1999 through 2010. Prognosis was compared in relation to the TNM seventh edition staging to serve as validation and analyzed in relation to proposed changes to the T descriptors found in the eighth edition. Results There were 5002 patients: 4848 patients with clinical and 582 with pathological stages. Among these, 428 had both. Survival differences were confirmed for T and N categories and maintained in relation to proposed revisions to T descriptors for seventh edition TNM categories and proposed changes in the eighth edition. There were also survival differences, notably at 12 months, in patients with brain-only single-site metastasis (SSM) compared to SSM at other sites, and SSM without a pleural effusion showed a better prognosis than other patients in the M1b category. Conclusion We confirm the prognostic value of clinical and pathological TNM staging in patients with SCLC, and recommend continued usage for SCLC in relation to proposed changes to T, N, and M descriptors for NSCLC in the eighth edition. However, for M descriptors, it remains uncertain whether survival differences in patients with SSM in the brain simply reflect better treatment options rather than better survival based on anatomic extent of disease.

Introduction: The current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition. Methods: Data elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded. An electronic data capture system was established to facilitate data submission. Results: A total of 3519 cases were submitted to the database. Of those eligible for T-component analysis, 509 cases had only clinical staging, 836 cases had only surgical staging, and 642 cases had both available. Survival was examined for T categories according to the current seventh edition staging system. There was clear separation between all clinically staged categories except T1a versus T1b (hazard ratio = 0.99, p = 0.95) and T3 versus T4 (hazard ratio = 1.22, p = 0.09), although the numbers of T4 cases were small. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category; no current descriptors were shifted or eliminated. Tumor thickness and nodular or rindlike morphology were significantly associated with survival. Conclusions: A recommendation to collapse both clinical and pathological T1a and T1b into a T1 classification will be made for the eighth edition staging system. Simple measurement of pleural thickness has prognostic significance and should be examined further with a view to incorporation into future staging. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Introduction Separate tumor nodules with the same histologic appearance occur in the lungs in a small proportion of patients with primary lung cancer. This article addresses how such tumors can be classified to inform the eighth edition of the anatomic classification of lung cancer. Separate tumor nodules should be distinguished from second primary lung cancer, multifocal ground glass/lepidic tumors, and pneumonic-type lung cancer, which are addressed in separate analyses. Methods Survival of patients with separate tumor nodules in the International Association for the Study of Lung Cancer database were analyzed. This was compared with a systematic literature review. Results Survival of clinically staged patients decreased according to the location of the separate tumor nodule relative to the index tumor (same lobe > same side > other side) in N0 and N-any cohorts (all M0 except possible other-side nodules). However, there was also a decrease in the proportion of patients resected; among only surgically resected or among nonresected patients no survival differences were noted. There were no survival differences between patients with same-lobe nodules and those with other T3 tumors, between patients with same-side nodules and those with T4 tumors, and patients with other-side nodules and those with other M1a tumors. The data correlated with those identified in a literature review. Conclusions Tumors with same-lobe separate tumor nodules (with the same histologic appearance) are recommended to be classified as T3, same-side nodules as T4, and other-side nodules as M1a. Thus, there is no recommended change between the seventh and eighth edition of the TNM classification of lung cancer.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23&ndash, 25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer.

Limited literature is available regarding treatment strategies for three concurrent potentially curable malignancies, and only one case of primary breast cancer with bilateral primary lung cancers has been reported. There is no literature available on approaches to radiation treatment planning and delivery in this challenging scenario. We report a case of a 66-year-old female who underwent partial mastectomy and sentinel node biopsy for left-sided breast cancer, pT1cN1(mic). Metastatic work-up revealed bilateral primary lung cancers, biopsy-proven, each Stage cT1N0. Distinguishing synchronous primary tumours from metastatic disease can be challenging. The histological examination suggested three distinct primaries and each was potentially curable. Devising a treatment strategy required balancing the incremental benefits with the toxicity of combining each of the treatments. Stereotactic ablative radiotherapy was the treatment of choice for the patient's lung primaries, as she was deemed a high-risk surgical candidate. Tangential whole breast radiotherapy with regional nodal irradiation was deemed appropriate for her breast cancer. Treatment for all three sites was planned concurrently, taking into account any potential overlap of dose in the composite plan. Each lung lesion was treated with 48 Gy in 4 fractions with stereotactic ablative radiotherapy using volumetric modulated arc therapy technique. The breast and supraclavicular regions were treated with 50 Gy in 25 daily fractions using a field-in-field technique. Optimal clinical outcomes for patients with multiple primary cancers require optimal definitive management. In this unique case of triple primaries, curative-intent radiotherapy to both lungs, the left breast and regional nodes was planned to be given concurrently and treatment was successfully delivered without significant toxicity.

In contemporary high-dose-rate brachytherapy treatment of superficial tumors, catheters are placed in a wax mould. The creation of current wax models is a difficult and time consuming proces.The irradiation plan can only be computed post-construction and requires a second CT scan. In case no satisfactory dose plan can be created, the mould is discarded and the process is repeated. The objective of this work was to develop an automated method to replace suboptimal wax moulding. We developed a method to design and manufacture moulds that guarantee to yield satisfactory dosimetry. A 3D-printed mould with channels for the catheters designed from the patient’s CT and mounted on a patient-specific thermoplastic mesh mask. The mould planner was implemented as an open-source module in the 3D Slicer platform. Series of test moulds were created to accommodate standard brachytherapy catheters of 1.70mm diameter. A calibration object was used to conclude that tunnels with a diameter of 2.25mm, minimum 12mm radius of curvature, and 1.0mm open channel gave the best fit for this printer/catheter combination. Moulds were created from the CT scan of thermoplastic mesh masks of actual patients. The patient-specific moulds have been visually verified to fit on the thermoplastic meshes. The masks were visually shown to fit onto the thermoplastic meshes, next the resulting dosimetry will have to be compared with treatment plans and dosimetry achieved with conventional wax moulds in order to validate our 3D printed moulds.