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Purpose: To investigate the feasibility of modeling Stage III lung cancer tumor and node positions from anatomical surrogates. Methods and Materials: To localize their centroids, the primary tumor and lymph nodes from 16 Stage III lung cancer patients were contoured in 10 equal-phase planning four-dimensional (4D) computed tomography (CT) image sets. The centroids of anatomical respiratory surrogates (carina, xyphoid, nipples, mid-sternum) in each image set were also localized. The correlations between target and surrogate positions were determined, and ordinary least-squares (OLS) and partial least-squares (PLS) regression models based on a subset of respiratory phases (three to eight randomly selected) were created to predict the target positions in the remaining images. The three-phase image sets that provided the best predictive information were used to create models based on either the carina alone or all surrogates. Results: The surrogate most correlated with target motion varied widely. Depending on the number of phases used to build the models, mean OLS and PLS errors were 1.0 to 1.4 mm and 0.8 to 1.0 mm, respectively. Models trained on the 0%, 40%, and 80% respiration phases had mean (± standard deviation) PLS errors of 0.8 ± 0.5 mm and 1.1 ± 1.1 mm for models based on all surrogates and carina alone, respectively. For target coordinates with motion >5 mm, the mean three-phase PLS error based on all surrogates was 1.1 mm. Conclusions: Our results establish the feasibility of inferring primary tumor and nodal motion from anatomical surrogates in 4D CT scans of Stage III lung cancer. Using inferential modeling to decrease the processing time of 4D CT scans may facilitate incorporation of patient-specific treatment margins. [Copyright &y& Elsevier]

Purpose: Respiratory-gated radiotherapy allows for the reduction of the toxicity associated with concomitant chemoradiotherapy, but the smaller fields used could increase the risk of missing the target. A prospective study was performed to evaluate the dosimetric consequences of time-trend changes in patients with lung cancer who were treated with concomitant chemoradiotherapy. Methods and Materials: A total of 24 lung cancer patients eligible for chemoradiotherapy and gated delivery underwent four-dimensional computed tomography (4D-CT) after 15 fractions. This scan was co-registered with the initial planning 4D-CT and a new planning target volume (PTV) was generated on the basis of the tumor visualized after 15 fractions. Coverage of the repeat PTV was evaluated by applying the original plan to the second scan and recalculating the dose. Plan modification was triggered by a 5% reduction in the PTV included within the 95% isodose volume or an unacceptable increase in the critical organ dose. Results: Of the 21 evaluable patients, 15 had an average reduction in the PTV of 8% after 30 Gy. The PTV increased in the remaining 6 patients, but the increase was >20% in only 1 patient. In the latter patient, disease progression was observed, and repeat planning was required. The plans created using the new PTV were acceptable in all the other patients. Conclusion: The role of adaptive radiotherapy appears limited when respiratory-gated radiotherapy is used to reduce the toxicity related to concomitant chemoradiotherapy. The use of more conformal treatment techniques might provide the rationale for repeat imaging as a method to identify patients at risk of dosimetric miss. [Copyright &y& Elsevier]

Purpose: The motion of mediastinal lymph nodes may undermine local control with involved-field radiotherapy. We studied patterns of nodal and tumor motion in 41 patients with lung cancer. Methods and Materials: Four-dimensional (4D) computed tomography planning scans were retrospectively evaluated to identify patients with clearly visible mediastinal lymph nodes. One hundred nodes from 14 patients with Stage I and 27 patients with Stage III were manually contoured in all 4D computed tomography respiratory phases. Motion was derived from changes in the nodal center-of-mass position. Primary tumors were also delineated in all phases for 16 patients with Stage III disease. Statistical analysis included a multivariate mixed-effects model of grouped data. Results: Average 3D nodal motion during quiet breathing was 0.68 cm (range, 0.17–1.64 cm); 77% moved greater than 0.5 cm, and 10% moved greater than 1.0 cm. Motion was greatest in the lower mediastinum (p = 0.002), and nodes measuring 2 cm or greater in diameter showed motion similar to that in smaller nodes. In 11 of 16 patients studied, at least one node moved more than the corresponding primary tumor. No association between 3D primary tumor motion and nodal motion was observed. For mobile primary tumors, phase offsets between the primary tumor and nodes of two or more and three or more phases were observed for 33% and 12% of nodes, respectively. Conclusions: Mediastinal nodal motion is common, with phase offsets seen between the primary tumor and different nodes in the same patient. Patient-specific information is needed to ensure geometric coverage, and adaptive strategies based solely on the primary tumor may be misleading. [Copyright &y& Elsevier]

OBJECTIVE To investigate the effect of smoking on the outcome in a cohort of men treated for localized prostate cancer at one institution with a uniform protocol of radical external beam radiotherapy (EBRT). PATIENTS AND METHODS The study was a retrospective review of 434 patients with cT1-T4 N0m0 prostate cancer treated with curative intent with EBRT (66 Gy in 33 fractions) between 1990 and 1999. Univariate and multivariate Cox regression analyses were used to estimate the risk associated with smoking on biochemical failure (American Society for Therapeutic Radiology and Oncology definition), local failure, distant failure, overall and disease-specific survival. RESULTS The median follow-up was 70.3 months. A smoking history was obtained in 96% of cases; 16.8% were current smokers, 54.4% previous smokers and 28.8% non-smokers. Current smokers presented at a younger median age, by 3.6 years ( P = 0.06). There were no differences in clinical T stage, Gleason score or prostate-specific antigen level amongst the three patient groups. Smoking conferred a higher risk of developing metastatic disease in both current smokers (hazard ratio 5.24; 95% confidence interval 1.75–15.72) and previous smokers (2.90, 1.09–7.67). There were also increases in risk, although not quite significant, for biochemical failure (1.49, 0.88–2.40) and overall survival (1.72, 0.94–3.15). CONCLUSIONS After curative treatment with EBRT, a history of smoking was associated with a greater risk of developing metastatic disease. Smoking status was not associated with worse disease on presentation. [ABSTRACT FROM AUTHOR]

Simple Summary: The very poor prognosis and the absence of radical treatment options in cases of unresectable "locally advanced pancreatic cancer (LAPC)" focus its management on palliation. An "overall survival (OS)" benefit has been shown with new systemic therapy agents; however, not all patients are good candidates for systemic treatments at diagnosis, and LAPC is often associated with a high symptom burden that greatly impacts patients' quality of life. Studying dose optimization of radiation as an option for local progression cessation is therefore necessary. Research in this setting as opposed to other treatment sites is under-represented in the literature and the guidelines are based on very scarce data. We aim to present the outcomes of "stereotactic body radiotherapy (SBRT)" (ablative radiotherapy) vs. non-ablative radiotherapy through our patient population and the available data in the literature. We studied the dose–local control (LC) relationship in ablative vs. non-ablative radiotherapy in a non-radical treatment setting of "locally advanced pancreatic cancer (LAPC)" by comparing our patients (n = 89) treated with SBRT on the CyberKnife unit vs. conventional radiation between January 2005 and January 2021, and by reviewing the literature. A systematic search was performed leveraging Medline for references on SBRT use in pancreatic cancer without date terms or language restrictions. A total of 3702 references were identified and the search was then repeated in Embase and the Cochrane database. Ultimately, 12 studies were eligible for inclusion, which either compared SBRT to conventional radiation, or SBRT use in dose escalation for primary LAPC in a non-neoadjuvant setting. Our cohort's median overall survival was 152 days (CI 95%, 118–185); including 371 days (CI 95%, 230–511) vs. 126 days (CI 95%, 90–161) favoring SBRT, p = 0.004. The median time to local progression was 170 days (48–923) for SBRT vs. 107 days (27–489) for the non-ablative group. In our SBRT patients, no local progressions were seen with BED10 > 60 Gy. Even when palliating LAPC, SBRT should be considered as an alternative to conventional radiation, especially in patients with a low disease burden. BED10 ≥ 60–70 Gy offers better local control without increasing toxicity rates. Less local progression may provide a better quality of life to those patients who already have a short life expectancy. [ABSTRACT FROM AUTHOR]

• The first pan-Canadian recommendations created to support equitable and timely access to quality proton therapy. • Input from experts across Canada, external peer-review, and community consultation included. • 27 consensus recommendations developed for patient eligibility, program and system levels. Proton Beam Therapy (PBT) is a treatment option for select cancer patients. It is currently not available in Canada. Assessment and referral processes for out-of-country treatment for eligible patients vary by jurisdiction, leading to variability in access to this treatment for Canadian cancer patients. The purpose of this initiative was to develop a framework document to inform consistent and equitable PBT access for appropriate patients through the creation of pan-Canadian PBT access consensus recommendations. A modified Delphi process was used to develop pan-Canadian recommendations with input from 22 PBT clinical and administrative experts across all provinces, external peer-review by provincial cancer and system partners, and feedback from a targeted community consultation. This was conducted by electronic survey and live discussion. Consensus threshold was set at 70% agreement. Four consensus rounds resulted in a final set of 27 recommendations divided into three categories: patient eligibility (n = 9); program level (n = 10); and system level (n = 8). Patient eligibility included: anatomic site (n = 4), patient characteristics (n = 3), clinical efficacy (n = 2). Program level included: regulatory and staff requirements (n = 5), equipment and technologies (n = 4), quality assurance (n = 1). System level included: referral process (n = 5), costing, budget impact and quality adjusted life years (n = 2), eligible patient estimates (n = 1). Recommendations were released nationally in June 2021 and distributed to all 43 cancer programs in Canada. A pan-Canadian consensus-building approach was successful in creating an evidence-based, peer-reviewed suite of recommendations that support application of consistent clinical criteria to inform treatment options, facility set-up and access to high quality proton therapy. [ABSTRACT FROM AUTHOR]

Ambulatory cancer centers face a fluctuating patient demand and deploy specialized personnel who have variable availability. This undermines operational stability through the misalignment of resources to patient needs, resulting in overscheduled clinics, budget deficits, and wait times exceeding provincial targets. We describe the deployment of a Learning Health System framework for operational improvements within the entire ambulatory center. Known methods of value stream mapping, operations research and statistical process control were applied to achieve organizational high performance that is data-informed, agile and adaptive. We transitioned from a fixed template model by an individual physician to a caseload management by disease site model that is realigned quarterly. We adapted a block schedule model for the ambulatory oncology clinic to align the regional demand for specialized services with optimized human and physical resources. We demonstrated an improved utilization of clinical space, increased weekly consistency and improved distribution of activity across the workweek. The increased value, represented as the ratio of monthly encounters per nursing worked hours, and the increased percentage of services delivered by full-time nurses were benefits realized in our cancer system. The creation of a data-informed demand capacity model enables the application of predictive analytics and business intelligence tools that will further enhance clinical responsiveness. [ABSTRACT FROM AUTHOR]

Background: To assess correlation of pretreatment specific growth rate (SGR) value of 0.43 × 10‐2 with overall and failure‐free survival of patients with early‐stage non‐small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods: A retrospective chart review of 160 patients with pathologically confirmed stage I NSCLC treated with SBRT between June 2010 and December 2012 in a large, tertiary cancer institute was undertaken. Both diagnostic and archived planning CT were uploaded to the treatment planning system to determine tumor volume at diagnosis (GTV1) and planning time (GTV2). The time (t) between both CTs was recorded. SGR was calculated using GTV1, GTV2, and t. The median SGR (0.43 × 10‐2) from our previous data was used to group patients into low and high SGR cohorts. Log‐rank test was used to compare overall (OS) and failure‐free survivals (FFS) of SGR groups. Results: The median time interval between diagnostic and planning CT scans was 87 days. The median OS was 38 and 66 months for high and low SGR cohorts, respectively (P = 0.03). The median FFS was 27 and 55 months for high and low SGR cohorts, respectively (P = 0.005). High SGR (P < 0.05), male gender (P = <0.01), and GTV2 (P = <0.05) were associated with poorer FFS. Conclusions: High SGR was associated with poorer outcome in patients with early‐stage NSCLC treated with SBRT. SGR can be used in conjunction with other well‐known predictive factors to formulate a practical predictive model to identify subgroups of the patient at higher risk of recurrence after SBRT. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer.Methods: The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0-2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up.Findings: Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35-58), median overall survival was 30 months (95% CI 24-34) in the twice-daily group versus 25 months (21-31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95-1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50-62) in the twice-daily group and 51% (45-57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI -3·2% to 13·7%]). The most common grade 3-4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3-4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3-4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group).Interpretation: Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting.Funding: Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups). [ABSTRACT FROM AUTHOR]

Background and objectives Standard management of stage II non-small cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. The optimal non-surgical management of stage II NSCLC is undefined. We surveyed Canadian oncologists to understand current practices. Materials and methods Canadian oncologists specializing in the management of lung cancer were invited by email to complete an anonymous, online survey developed by the research team. Physician demographics were recorded. Physicians were asked to comment on their practice and make treatment choices in eight clinical scenarios of inoperable stage II NSCLC. Results Responses were received from 81/194 physicians (42% response rate), 57% medical and 42% radiation oncologists. Most physicians (90%) had a practice with at least 25% lung cancer patients and 85% were based at an academic institution. Across eight clinical patient scenarios, radical therapy was selected 79–98% of the time. Radical radiotherapy alone and concurrent chemoradiotherapy were the preferred options for these patients, while sequential chemoradiation was less favoured. Nodal status (N0 vs N1) did not influence choice of therapy (p 0.31), but the reason for patient inoperability did (p < 0.0001). There was no significant difference in choice of therapy when comparing responses between medical vs radiation oncologists, academic vs community physicians, and physicians with high vs low proportion of lung cancer patients. Conclusion Most lung cancer physicians manage inoperable stage II NSCLC patients with curative intent, but consensus on how to optimally employ radiotherapy and/or chemotherapy is lacking. Future prospective, randomized trials are warranted. [ABSTRACT FROM AUTHOR]

Background and Purpose: The purpose of this study is to review our experience with platinum fiducials in terms of feasibility of placement and detectability by both MRI and orthogonal x-ray images used in robotic SABR. Materials and Methods: 29 consecutive SABR patients (30 tumors) treated using fiducial tracking between January 2011 and February 2012 were reviewed. A total of 108 fiducials implanted in or around various tumor sites were identified. The pixel value contrast (PVC) of fiducials seen on MRI mages and treatment unit x-ray images of patients and phantoms were analysed. Results: Migration rates were similar for PS versus GS and GC (6.2%). No difference was noted between the mean PVC in cirrhotic versus non-cirrhotic liver (60.4 vs. 47.9; p = 0.074). MRI sequences for tumors in the liver and other organs revealed a mean PVC for platinum superior to that of gold (p<0.001). No PVC difference was seen between gold and platinum on analysis of the treatment unit x-rays. Conclusion: Platinum seeds provide a superior detectability in comparison to gold seeds or coils on MRI images and are detected equally well by an image guidance system using orthogonal x-rays, making them a better choice for fiducial-based CT-MRI registration. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUVmax) of the primary tumor for [(18)F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUVmax were 8.1 and 7, respectively. Progression-free survival at 2 years with SUVmax <7 was better than that of the patients with tumor SUVmax ≥7 (67% vs 51%; P=.0096). Tumors with SUVmax ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUVmax ≥7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUVmax ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUVmax) of the primary tumor for [18F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUVmax were 8.1 and 7, respectively. Progression-free survival at 2 years with SUVmax <7 was better than that of the patients with tumor SUVmax ≥7 (67% vs 51%; P=.0096). Tumors with SUVmax ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUVmax ≥7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUVmax ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes. [Copyright &y& Elsevier]

Abstract: Purpose: A new 4D in vivo dosimetry tool, RADPOS, has been used on lung cancer patients to evaluate the feasibility of using the detectors to characterize variations in patient breathing patterns as well as to monitor daily variations in dose. Methods and materials: The RADPOS system combines a MOSFET dosimeter with an electromagnetic positioning sensor for simultaneous measurement of real-time dose and spatial coordinates. Three RADPOS sensors were placed on patients’ chest and abdomen during a 4DCT and daily treatments. A fourth detector was also placed on the couch as reference. Position data were collected in real-time and total dose was read at the end of each fraction. Results: Significant deviations in surface motion have been found between the day of 4DCT and treatment fractions in 9 of 10 patients. Variations in daily dose ranged from 2.5 to 13.7cGy (2.8–14.0%) and results agreed with treatment plan values for all but three points. Conclusions: Changes in breathing motion have been found that emphasize a need for continued position monitoring. RADPOS measurements can be used to monitor such variations as well as to measure surface dose without any disruption to the treatment schedule or discomfort to patients. [Copyright &y& Elsevier]