A Clinical Consensus Approach to Developing a New Funding Model for Radiation Services in Ontario.

In 2021, Ontario Health (Cancer Care Ontario) introduced a quality-based procedure model for the funding of radiation treatment (RT) in Ontario. This model ties reimbursement to patient care activities, ensuring equity and transparency in funding. Over 200 RT interprofessionals (oncologists, therapists and physicists) participated on 22 expert panels to establish or identify 288 evidence-based RT protocols and 672 quality expectations (QEs) to optimally deliver RT, which eventually led to the micro-costing of all protocols. Iterative review is required to ensure updated techniques and identify evolving standards of care, thereby providing the highest quality of RT care to Ontarians.

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.

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).

Assessment of function and quality of life in a phase II multi-institutional clinical trial of fractionated simultaneous in-field boost radiotherapy for patients with 1-3 metastases.

We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1-3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30 Gy/10) + simultaneous FSRT, (60 Gy/10). Median overall follow-up and survival was 5.4 months, 6 month actuarial intra-lesional control was 78 %; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to <27) ranged from 26 to 38 % for KPS, 32-59 % for FACT-Br and 0-16 % for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (≤6 months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. The effects on function and quality of life of this integrated treatment of WBRT + simultaneous FSRT were similar to other published series combining WBRT + radiosurgery.

CyberKnife for inoperable renal tumors: Canadian pioneering experience.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is currently under study regarding its clinical application in management of patients with kidney tumors. CyberKnife can accurately deliver ablative tumor radiation doses while preserving kidney function. We report Canada's first use of CyberKnife SABR system in treating primary kidney tumors. MATERIALS AND METHODS: Between January 2011 and February 2012, we treated three patients with renal tumors using CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient had a recurrent tumor after two previous radiofrequency ablation treatments. Platinum seed fiducials were used for real time tumor tracking. Magnetic resonance imaging registration was used for tumor delineation in all cases. The patients were followed with regular renal scans and renal function tests. RESULTS: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy in 3 fractions was delivered. The post treatment follow up times were 15 months, 13 months and 12 months. Local control was obtained in all three patients. No acute or chronic toxicity was reported. Kidney functions remained unaffected after treatment. CONCLUSION: CyberKnife is technically feasible for treatment of medically inoperable renal tumors or tumors in a solitary kidney.

Ablative vs. Non-Ablative Radiotherapy in Palliating Locally Advanced Pancreatic Cancer: A Single Institution Experience and a Systematic Review of 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.

Cancer Clinic Redesign: Opportunities for Resource Optimization.

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.

Pan-Canadian consensus recommendations for proton beam therapy access in Canada.

PURPOSE: 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. MATERIALS AND METHODS: A modified Delphiprocess 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. RESULTS: Fourconsensus 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. CONCLUSION: A pan-Canadian consensus-building approach was successful in creating an evidence-based, peer-reviewed suite of recommendations thatsupportapplication of consistent clinical criteria to inform treatment options, facility set-up and access to high quality proton therapy.

Validating impact of pretreatment tumor growth rate on outcome of early-stage lung cancer treated with stereotactic body radiation therapy.

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.

Adrenal oligometastasis cured with stereotactic ablative radiotherapy.

Stereotactic ablative radiotherapy (SABR) has emerged as an effective, noninvasive alternative to surgery in patients with oligometastatic disease. Historically, select patients with adrenal oligometastases have been treated with adrenalectomies which can offer durable local control and reasonable survival rates. SABR is a promising noninvasive treatment alternative to surgery capable of delivering ablative doses of radiation to the tumor with the goal of achieving durable local control of adrenal metastases. We report on a case of a patient who underwent initial surgical resection for a locally advanced lung adenocarcinoma and subsequently developed an early, biopsy-proven, oligometastatic recurrence in the adrenal gland. He underwent chemotherapy and SABR using CyberKnife to the adrenal metastasis and is in remission 7 years after treatment with no late toxicity. Fractionated SABR is an attractive noninvasive alternative to surgery for adrenal metastases. This case demonstrates that select patients with adrenal oligometastases, can achieve long-term remission and even cure following SABR.

Clinical Specialist Radiation Therapist in Palliative Radiation Therapy: Report of an Orientation, Training, and Support Program.

INTRODUCTION: A clinical specialist radiation therapist (CSRT) position in palliative radiation therapy (RT) was created at our institution. Herein, we report the details of the CSRT's orientation, training, and support program. METHODS: We performed an audit and needs assessment of palliative RT services at our centre. This identified opportunities for improvement that could be facilitated by the CSRT. We defined the CSRT job description including priority responsibilities: (1) optimizing palliative RT services for outpatients and developing a rapid access palliative RT program, (2) optimizing palliative RT services for inpatients at our institution, (3) improving links to community physicians and hospitals caring for patients with advanced cancers. We formed a core resource team to provide ongoing support and to design and implement the orientation and training program. The program involved training in clerical and administrative systems as well as treatment planning and physics training relevant to palliative RT. Clinical placements at several hospitals were arranged in both inpatient and outpatient settings. The CSRT worked with radiation and medical oncologists, palliative care specialists, nurse practitioners, hospitalists, and social workers. RESULTS: Through clinical placements and self-directed learning, the CSRT gained knowledge and competencies in patient care coordination, history taking and physical examination, clinical oncology practice including the evidence-based use of palliative RT and symptom control measures, treatment planning, communication, patient advocacy, and advance care planning. We provided practice resources including office space and a planning station, educational opportunities including workshops in palliative and psychosocial care, and research opportunities including methodologic and research ethics training. DISCUSSION: To our knowledge, this is the first detailed report of its kind for an advanced practice radiation therapy role. We hope our report will inform the design and implementation of programs elsewhere to help prepare individuals for similar roles in palliative RT. CONCLUSION: The CSRT in palliative RT at our institution underwent a comprehensive orientation and training program. Institutions with similar CSRT positions are encouraged to report the details of their own programs.

Anemia is a poor prognostic factor for stage I non-small cell lung cancer (NSCLC) patients treated with Stereotactic Body Radiation Therapy (SBRT).

•This study reports on the prognostic ability of haematological parameters for the largest known biopsy-proven stage-I medically inoperable cohort treated with SBRT.•After SBRT, the median values of Hb, ALC, ANC and TPC declined whereas the NLR and the PLR increased as compared to pre-SBRT.•Anemia along with other parameters was found to be a poor prognostic factor for local control despite treatment with SBRT to doses of >100 Gy BED10.•Simple and minimally invasive methods like a peripheral blood sample can provide prognostic information even for stage-I NSCLC patients.•Patient, tumor and treatment factors along with molecular markers should be used to create risk stratification models that can guide therapy.

Radiation dose mapping and anastomotic complications after trimodality therapy for esophageal cancers.

BACKGROUND AND PURPOSE: There is conflicting evidence with respect to the correlation between neoadjuvant chemoradiation and anastomotic complications following trimodality therapy in patients with esophageal cancer. We aimed to analyze the relationship between their dosimetry and any resulting anastomotic complications. MATERIALS AND METHODS: The medical records of 51 consecutive patients who underwent trimodality therapy between 2007 and 2014 were retrospectively reviewed. We analyzed the differences in the mean dose received by regions of the esophagus relative to the landmark of the azygous vein and the stomach to correlate the development of an anastomotic complication using nonparametric rank-sum tests. RESULTS: Anastomotic leakage and stricture rates were 12% and 22%, respectively. Patients with anastomotic complications received a statistically significant higher mean dose to the esophagus at the level of the azygous vein (0.0 cm) and lower (up to -2.7 cm) (28.4-42.2 Gy vs. 10.3-27.6 Gy, p < 0.04). There were no differences noted in mean gastric doses. Median follow up time was 30.9 months. Median overall survival and disease free survival of our patient cohort was 34.4 months and 22.5 months, respectively. The development of an anastomotic complication did not affect survival outcomes. CONCLUSION: Patients who experienced anastomotic complication after trimodality therapy for esophageal cancer were more likely to have received a higher mean esophageal dose around the proximity of the azygous vein, where intrathoracic anastomoses most commonly occur. Communication between surgical and radiation oncologists regarding the anastomotic location may be an important consideration in planning for trimodality therapy in reducing potential anastomotic complications.

A Phase II Multi-institutional Clinical Trial Assessing Fractionated Simultaneous In-Field Boost Radiotherapy for Brain Oligometastases.

Purpose/Objective Published preclinical and phase I clinical trial data suggest that fractionated lesional radiotherapy with 60 Gy in 10 fractions can serve as an alternative approach to single fraction radiosurgical boost for brain oligometastases.  Methods and Materials A phase II clinical trial (NCT01543542) of a total of 60 Gy in 10 fractions of lesional (one to three) radiotherapy (given simultaneously with whole-brain helical tomotherapy with 30 Gy in 10 fractions) was conducted at five institutions. We hypothesized that fractionated radiotherapy would be considered unsuitable if the median overall survival (OS) was degraded by two months or if six-month intracranial control (ICC) and intracranial lesion (ILC) were inferior by 10% compared with the published RTOG 9508 results. Results A total of 87 patients were enrolled over a 4.5-year accrual period. Radiological lesion and extralesional central nervous system progression were documented in 15/87 (17%) and 11/87 (13%) patients, respectively. Median OS for all patients was 5.4 months. Six-month actuarial estimates of ICC and ILC were 78% and 89%, respectively. However, only the ILC estimate achieved statistical significance (p=0.02), demonstrating non-inferiority to the a priori historical controls (OS: p=0.09, ICC=0.31). Two patients developed suspected asymptomatic radionecrosis. Conclusions The phase II estimates of ILC were demonstrated to be non-inferior to the results of the RTOG 9508.

Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non-Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial.

PURPOSE: Patients with centrally located early-stage non-small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS: Medically inoperable patients with biopsy-proven, positron emission tomography-staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS: One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION: The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

Radical Treatment of Stage II Non-small-cell Lung Cancer With Nonsurgical Approaches: A Multi-institution Report of Outcomes.

INTRODUCTION: 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. We examined outcomes in this defined patient group. METHODS: We reviewed the records of patients with stage II NSCLC treated nonsurgically with curative intent from 2002 to 2012 across 3 academic cancer centers. Data collected included demographics, comorbidities, staging, treatments, and survival. The primary endpoint was overall survival (OS). We assessed factors associated with treatment choice and OS. RESULTS: A total of 158 patients were included: the median age was 74 years (range, 50-91 years), 44% were female, and 68% had a performance status of 0 to 1. The stage II groupings of the patients were T2b-T3 N0 in 55% and N1 in 45%. The most common reasons for inoperability were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median, 60 Gy [range, 48-75 Gy]). Seventy-three percent received RT alone; 24% received concurrent and 3% sequential chemoradiotherapy (CRT). In multivariate analyses, CRT was less likely in older patients (≥ 70 years) (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.70; P = .006) and in patients with higher (> 5) Charlson comorbidity scores (OR, 0.34; 95% CI, 0.13-0.90; P = .03) or normal (< 10 × 109/L) white blood cell counts (OR, 0.26; 95% CI, 0.09-0.73; P = .01). At the time of our analysis, 74% have died. The median OS was 22.9 months (range, 17.1-26.6 months). Patients who had undergone CRT had a significantly longer median OS than those receiving RT alone (39.1 vs. 20.5 months; P = .0019), confirmed in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21-0.69; P = .001). CONCLUSION: Nonsurgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared with RT alone. A randomized trial may be warranted.

Age-not Charlson Co-morbidity Index-predicts for mortality after stereotactic ablative radiotherapy for medically inoperable stage I non-small cell lung cancer.

PURPOSE: In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). METHODS: Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50-60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0-1, 2-3, 4-9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed. RESULTS: The median survival was 4.4 years and the median follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7-12 had an increased hazard of death on univariate analysis HR 2.45 (1.15-5.22 95%CI, p = 0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04-4.84 95%CI, p = 0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30-2.90) but not on multivariate analysis. On formalized testing - with either continuous or categorical variables- all three survival models yielded similar coefficients of effect. CONCLUSION: We identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

Quantitative texture analysis on pre-treatment computed tomography predicts local recurrence in stage I non-small cell lung cancer following stereotactic radiation therapy.

BACKGROUND: The prediction of local recurrence (LR) of stage I non-small cell lung cancer (NSCLC) after definitive stereotactic body radiotherapy (SBRT) remains elusive. The purpose of this study was to assess whether quantitative imaging features on pre-treatment computed tomography (CT) can predict LR beyond 18 (18F) fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT maximum standard uptake value (SUVmax). METHODS: This retrospective study evaluated 36 patients with 37 stage I NSCLC who had local tumor control (LC; n=19) and (LR; n=18). Textural features were extracted on pre-treatment CT. Mann-Whitney U tests were used to compare LC and LR groups. Receiver-operating characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated with LR as outcome. RESULTS: Gray-level correlation and sum variance were greater in the LR group, compared with the LC group (P=0.02 and P=0.04, respectively). Gray-level difference variance was lower in the LR group (P=0.004). The logistic regression model generated using gray-level correlation and difference variance features resulted in AUC (SE) 0.77 (0.08) (P=0.0007). The addition of 18F-FDG PET/CT SUVmax did not improve the AUC (P=0.75). CONCLUSIONS: CT textural features were found to be predictors of LR of early stage NSCLC on baseline CT prior to SBRT.

Approach to the non-operative management of patients with stage II non-small cell lung cancer (NSCLC): A survey of Canadian medical and radiation oncologists.

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.

Treatment of metastatic liver tumors using stereotactic ablative radiotherapy.

The prognosis of patients with metastatic liver disease remains dismal with a median survival of only 6-12 mo. As 80%-90% of patients are not candidates for surgical therapy, there is a need for effective non-surgical therapies that would improve outcomes in these patients. The body of evidence related to the use of stereotactic ablative radiotherapy (SABR) in metastatic liver disease has substantially grown and evolved over the past decade. This review summarizes the current evidence supporting liver SABR with particular attention given to patient selection, target delineation, organ at risk dose volume constraints, response evaluation imaging and the various SABR techniques for delivering ablative radiotherapy to the liver. Even though it is unclear what dose-fractionation scheme, delivery system, concomitant therapy or patient selection strategy yields the optimum liver SABR outcomes, clear and growing evidence is available that SABR is a safe and effective therapy for the treatment of oligometastatic liver disease.

Pretreatment [18F]-fluoro-2-deoxy-glucose positron emission tomography maximum standardized uptake value as predictor of distant metastasis in early-stage non-small cell lung cancer treated with definitive radiation therapy: rethinking the role of positron emission tomography in personalizing treatment based on risk status.

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.