J. Cho

Patterns of Care in Elderly Head-and-Neck Cancer Radiation Oncology Patients: A Single-Center Cohort Study

PURPOSEnTo compare the patterns of care for elderly head-and-neck cancer patients with those of younger patients.nnnMETHODS AND MATERIALSnA retrospective review was conducted of all new mucosal head-and-neck cancer referrals to radiation oncology between July 1, 2003 and December 31, 2007 at our institution. The clinical characteristics, treatment pattern, tolerance, and outcomes were compared between the elderly (aged ≥75 years) and younger (aged <75 years) cohorts.nnnRESULTSnA total of 2,312 patients, including 452 (20%) elderly and 1,860 (80%) younger patients, were studied. The elderly patients were more likely to be women (36% vs. 27%, p <.01) and to have other malignancies (23% vs. 13%, p <.01), Stage I or II disease (38% vs. 32%, p <.01), and N0 status (56% vs. 42%, p <.01). Treatment was less often curative in intent (79% vs. 93%, p <.01). For the 1,487 patients who received definitive radiotherapy (RT), no differences were found between the elderly (n = 238) and younger (n = 1,249) patients in treatment interruption, completion, or treatment-related death. Within the subset of 760 patients who received intensified treatment (concurrent chemoradiotherapy or hyperfractionated accelerated RT), no difference was seen between the elderly (n = 46) and younger (n = 714) patients in treatment interruption, completion, or treatment-related death. After a median follow-up of 2.5 years, the 2-year cause-specific survival rate after definitive RT was 72% (range, 65-78%) for the elderly vs. 86% (range, 84-88%) for the younger patients (p <.01).nnnCONCLUSIONnElderly head-and-neck cancer patients exhibited different clinical characteristics and experienced different patterns of care from younger patients. Although age itself was an adverse predictor of cause-specific survival, its effect was modest. Elderly patients selected for definitive RT or intensified RT showed no evidence of impaired treatment tolerance.

Effect of Image-Guidance Frequency on Geometric Accuracy and Setup Margins in Radiotherapy for Locally Advanced Lung Cancer

PURPOSEnTo assess the relative effectiveness of five image-guidance (IG) frequencies on reducing patient positioning inaccuracies and setup margins for locally advanced lung cancer patients.nnnMETHODS AND MATERIALSnDaily cone-beam computed tomography data for 100 patients (4,237 scans) were analyzed. Subsequently, four less-than-daily IG protocols were simulated using these data (no IG, first 5-day IG, weekly IG, and alternate-day IG). The frequency and magnitude of residual setup error were determined. The less-than-daily IG protocols were compared against the daily IG, the assumed reference standard. Finally, the population-based setup margins were calculated.nnnRESULTSnWith the less-than-daily IG protocols, 20-43% of fractions incurred residual setup errors ≥ 5 mm; daily IG reduced this to 6%. With the exception of the first 5-day IG, reductions in systematic error (∑) occurred as the imaging frequency increased and only daily IG provided notable random error (σ) reductions (∑ = 1.5-2.2 mm, σ = 2.5-3.7 mm; ∑ = 1.8-2.6 mm, σ = 2.5-3.7 mm; and ∑ = 0.7-1.0 mm, σ = 1.7-2.0 mm for no IG, first 5-day IG, and daily IG, respectively. An overall significant difference in the mean setup error was present between the first 5-day IG and daily IG (p < .0001). The derived setup margins were 5-9 mm for less-than-daily IG and were 3-4 mm with daily IG.nnnCONCLUSIONnDaily cone-beam computed tomography substantially reduced the setup error and could permit setup margin reduction and lead to a reduction in normal tissue toxicity for patients undergoing conventionally fractionated lung radiotherapy. Using first 5-day cone-beam computed tomography was suboptimal for lung patients, given the inability to reduce the random error and the potential for the systematic error to increase throughout the treatment course.

Practical Considerations Arising from the Implementation of Lung Stereotactic Body Radiation Therapy (SBRT) at a Comprehensive Cancer Center

Introduction: With the anticipation of improved outcomes, especially for patients with early-stage non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has been rapidly introduced into the thoracic radiation oncology community. Although at first glance lung SBRT might seem methodologically similar to conventional radiotherapy, there are important differences in its execution that require particular consideration. The objective of this paper is to highlight these and other issues to contribute to the safe and effective diffusion of lung SBRT. We discuss practical challenges that have been encountered in the implementation of lung SBRT at a single, large institution and emphasize the importance of a systematic approach to the design of lung SBRT services. Methods: Specific technical and clinical components that were identified as being important during the development of lung SBRT at Princess Margaret Hospital are described. The clinical system that evolved from these is outlined. Results: Using this clinical framework the practical topics addressed include: patient assessment, simulation and treatment planning, tumor and organ at risk delineation, trial set up before treatment, on-line image-guidance, and patient follow-up. Conclusions: The potential gain in therapeutic ratio that is theoretically possible with lung SBRT can only be realized if the tumor is adequately irradiated and normal tissue spared. A discussion of the component parts of lung SBRT is presented. It is a complex process and specific challenges need to be overcome to effect the satisfactory transition of lung SBRT into routine practice.

Phase I Trial of Radiation With Concurrent and Consolidation Pemetrexed and Cisplatin in Patients With Unresectable Stage IIIA/B Non–Small-Cell Lung Cancer

PURPOSEnTo evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC).nnnMETHODS AND MATERIALSnEligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m(2) on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m(2) Days 1-3 for Dose Levels 1-3; 20 mg/m(2) Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m(2), 75 mg/m(2)) 21 days apart, after concurrent therapy.nnnRESULTSnBetween January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%.nnnCONCLUSIONSnFull systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.

Clinical outcomes of extensive stage small cell lung carcinoma patients treated with consolidative thoracic radiotherapy.

UNLABELLEDnThe purpose of this review was to determine the effect of consolidative thoracic radiotherapy (TRT) in patients with extensive stage small cell lung cancer (ES-SCLC) with minimal metastatic disease. Locoregional failure, distant failure and OS were 39%, 74% and 14% respectively at 2 years. No patients experienced clinical pneumonitis. Consolidative TRT is well tolerated in selected patients with ES-SCLC.nnnOBJECTIVESnTo determine the rates of loco-regional (LR) failure and toxicity in extensive-stage small cell lung carcinoma (ES-SCLC) patients treated with consolidative thoracic radiotherapy (TRT).nnnMETHODSnA retrospective review was conducted on SCLC patients treated from January 2005 to July 2009. Patients with ES-SCLC who received consolidative TRT ≥30Gy were identified. Sites of disease failure, toxicity Common Terminology Criteria for Adverse Events version 3.0, incidence, and cause of treatment delays and vital status were determined. The cumulative LR and distant failure rates were calculated. Progression-free and overall survivals (OS) were determined by the Kaplan-Meier method.nnnRESULTSnThree hundred thirty-six patients were identified with a diagnosis of SCLC and 215 patients had ES-SCLC. Nineteen (9%) patients were identified as receiving ≥30Gy consolidative TRT. Of this subgroup, the median age was 60 years (range 47 years to 82 years) and the median follow-up was 13 months (range 8 months to 32 months). Consolidative TRT was 40Gy/15 fractions (n = 16), 45Gy/30 fractions delivered twice daily (n = 2) and 36Gy/12 fractions (n = 1). Chemotherapy was sequential (n = 11) or concurrent (n = 8) with consolidative TRT. The incidence of LR failure was 26% and 39% at 1 and 2 years, respectively. The incidence of distant failure was 58% and 74% at 1 and 2 years, respectively. The median OS was 14 months. The 1-year and 2-year OS was 58% and 14%, respectively. No patients experienced clinical pneumonitis requiring treatment.nnnCONCLUSIONSnConsolidative TRT controlled LR disease in most patients with minimal acute toxicity, though distant failure remained a significant problem.

Volumetric Image Guidance Using Carina vs Spine as Registration Landmarks for Conventionally Fractionated Lung Radiotherapy

PURPOSEnTo compare the relative accuracy of 2 image guided radiation therapy methods using carina vs spine as landmarks and then to identify which landmark is superior relative to tumor coverage.nnnMETHODS AND MATERIALSnFor 98 lung patients, 2596 daily image-guidance cone-beam computed tomography scans were analyzed. Tattoos were used for initial patient alignment; then, spine and carina registrations were performed independently. A separate analysis assessed the adequacy of gross tumor volume, internal target volume, and planning target volume coverage on cone-beam computed tomography using the initial, middle, and final fractions of radiation therapy. Coverage was recorded for primary tumor (T), nodes (N), and combined target (T+N). Three scenarios were compared: tattoos alignment, spine registration, and carina registration.nnnRESULTSnSpine and carina registrations identified setup errors ≥ 5 mm in 35% and 46% of fractions, respectively. The mean vector difference between spine and carina matching had a magnitude of 3.3 mm. Spine and carina improved combined target coverage, compared with tattoos, in 50% and 34% (spine) to 54% and 46% (carina) of the first and final fractions, respectively. Carina matching showed greater combined target coverage in 17% and 23% of fractions for the first and final fractions, respectively; with spine matching, this was only observed in 4% (first) and 6% (final) of fractions. Carina matching provided superior nodes coverage at the end of radiation compared with spine matching (P=.0006), without compromising primary tumor coverage.nnnCONCLUSIONnFrequent patient setup errors occur in locally advanced lung cancer patients. Spine and carina registrations improved combined target coverage throughout the treatment course, but carina matching provided superior combined target coverage.

Outcome following IMRT for T2 glottic cancer: the potential impact of image-guidance protocols on local control

ObjectiveThis study aims to report on the outcome of intensity-modulated radiation therapy (IMRT) for T2 glottic cancer and the impact of changes in image-guidance protocol on local control. The result is compared to a historical cohort treated to the same dose with parallel-opposed pairs radiotherapy (POP).MethodsPatients with T2N0M0 glottic cancers who received primary radiotherapy (60xa0Gy/25 fractions/5xa0weeks) between July 1, 2003 and March 30, 2010 were included. The gross tumor volume (GTV) was delineated according to endoscopy/radiology. The clinical target volume (CTV) for POP encompassed the whole larynx with 60xa0Gy. IMRT generally treated partial laryngeal volumes comprising two CTVs: CTV1 (GTV+ 0.3∼0.5xa0cm, receiving 60xa0Gy) and CTV2 (GTV+ ≥1.0xa0cm, receiving 50xa0Gy). Planning target volumes (PTVs) were CTVs+ 0.5xa0cm. Local control (LC) in the IMRT cohort were stratified by image-guidance protocols: matching to bone vertebrae (IMRT-bone, treated prior to 2008) or to laryngeal tissue (IMRT-laryngeal_tissue, treated after 2008), and compared to the POP cohort.ResultsSeventy IMRT (44 IMRT-bone and 26 IMRT-laryngeal_tissue) and 48 POP patients were identified. The 3-year LC was 81xa0% (95xa0% CI 65–90) for the POP and 77xa0% (95xa0% CI 64–85) for the IMRT cohorts (pu2009=u20090.52). The IMRT-bone cohort had decreased LC compared with IMRT-laryngeal_tissue (69 vs. 91xa0%, pu2009=u20090.03). A trend towards increasing local failure for IMRT-bone vs. IMRT-laryngeal_tissue remained after adjusting for various tumor factors.ConclusionsThis modest cohort study demonstrates a comparable LC with IMRT for T2 glottic cancers compared to our historical POP cohort. It adds clinical evidence to previous technical observations that have hypothesized a potential impact of laryngeal_tissue movement independent of bone_vertebrae, when partial laryngeal irradiation is contemplated.

Classification and Reporting of Late Radiographic Changes After Lung Stereotactic Body Radiotherapy: Proposing a New System.

UNLABELLEDnRadiation-induced parenchymal lung changes after stereotactic body radiotherapy are common, and can obscure the primary tumor site. In this study we propose a structured radiographic reporting tool for characterization of these changes, pilot its feasibility in a group of radiation oncologists, and test the interrater agreement. We could demonstrate the applicability of the scale, with a fair to moderate agreement.nnnBACKGROUNDnThe purpose of the study was to design and pilot a synoptic scale for characterization of late radiographic changes after lung stereotactic body radiotherapy (SBRT).nnnPATIENTS AND METHODSnA participatory design process involving 6 radiation oncologists and 2 thoracic radiologists was used in the scales design. Seventy-seven early-stage non-small-cell lung cancer patients who were treated with SBRT were included, and after treatment their serial computed tomography (CT) images were scored by 6 radiation oncologists. Gwets First-order Agreement Coefficient (AC1) and a leave-one-out (LOO) analysis was used to assess interrater reliability and variability among raters, respectively.nnnRESULTSnThe scale reports on 5 independent categories including tumor in primary site, tumor in involved lobe, consolidation, volume loss, and ground-glass or interstitial changes. At each time point, each category is reported as increased, stable, decreased, obscured, or not present, compared with the previous. The total number of rated images for the pilot ranged from 450 at 6 months to 84 at 48 months. The primary tumor site was scored as obscured in 38% to 40% of ratings from 12 months onward; 3% to 5% of primary tumors were scored as increased. Consolidation, volume loss, and ground-glass or interstitial changes were increasingly marked as stable with time. At 24 months, AC1 was 0.28 (LOO, 0.22-0.42), 0.47 (LOO, 0.39-0.72), 0.45 (LOO, 0.42-0.50), 0.21 (LOO, 0.15-0.26), and 0.25 (LOO, 0.20-0.38) for the 5 categories listed, respectively.nnnCONCLUSIONnIn a population of clinicians, this scale could be implemented to characterize evolving lung changes after SBRT, and had fair to moderate interrater agreement. Obscured tumor site is a common challenge of follow-up CT imaging, and new imaging techniques should be explored. This scale provides a tool for communicating changes after SBRT.

Refining UICC TNM Stage and Prognostic Groups for HPV-Related Oropharyngeal Carcinomas

Purpose/Objective(s): The current TNM staging for oropharyngeal cancer (OPC) was designed empirically for HPV-unrelated [HPV(-)] disease. Emerging evidence suggests it is unsuited for HPV-related [HPV(+)] OPC. This study refines stage grouping for HPV(+) OPC patients and proposes additional prognostic risk groups within the guidelines of the UICC/AJCC TNM framework. Materials/Methods: We retrospectively analyzed a prospectively assembled OPC cohort treated with primary radiotherapy with or without chemotherapy from 2000-2010. Overall survival (OS) was compared among the current TNM stages (I-IV) for HPV(+) and HPV(-) patients separately. Recursive partitioning analysis (RPA) with ordinal T and N elements derived new RPA-stages objectively. Cox regression calculated relative mortality risk (RMR) to derive additional RMR-stages. The performance of RPAand RMR-stages was assessed against current UICC stages in predicting OS based on 4 widely accepted criteria: hazard consistency within each stage level; hazard discrimination between stage levels; outcome prediction, and sample size balance. Prognostic risk groups were further derived by RPA combining T-, N-classification, age, and smoking pack-years (PY). Results: A total of 810 HPV ascertained (by p16 staining) non-metastatic OPCs were identified, including 573 HPV(+) (UICC stage I: 8; II: 25; III: 79; IV: 461) and 237 HPV(-) (I: 8; II: 31; III: 38; IV: 160) OPC. Median follow up was 5.1 years. Reduced 3-year OS with higher UICC TNM stage was evident for HPV(-) (88, 67, 62, and 39% respectively, p=0.003). However, OS was similar within HPV(+) (88, 87, 81, and 80% respectively, p=0.712). RPA and RMR methods were applied to the HPV(+) cohort to refine current UICC stage groupings. RPA divided non-metastatic HPV(+) into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3) with corresponding 3-year OS of 88, 81, and 63%, respectively (p<0.001). M1 disease (20% OS at 3-years) was classified as RPA-stage IV. RMR also provided a valid stage grouping scheme (not shown) but was more cumbersome compared to RPA-stage. RPA-stage and RMR-stage were the two best stage groupings while UICC stages performed least well. Prognostic risk grouping by RPA sub-divided all HPV(+) into: group I (T13N0-N2c _<=20 PY), group IIA (T1-3N0-N2c_>20 PY), group IIB (T4 or N3, age <=70), group III (T4 or N3, age >70), and group IV (M1 disease), with corresponding 3-year OS of 93, 74, 67, 44, and 20% respectively. Conclusions: This large cohort study confirms that current UICC TNM stage is unsuited for HPV(+) OPC although acceptable for HPV(-). A refined RPA-based TNM stage grouping significantly improved survival prediction performance for HPV(+) OPC. Prognostic risk groupings are further enhanced by incorporating non-anatomical factors. The result should be validated in an independent dataset.