Participation and Functional Independence in Adults With Recessive Spastic Ataxia of Charlevoix-Saguenay.

Background. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a progressive disorder where upper and lower extremities motor performances may bring participation restriction. Purpose. To document participation in adults with ARSAC and explore associations with motor performances. Method. Twenty-eight participants took part in the study. Participation was assessed using the LIFE-H. Motor performance was assessed using several outcomes including the SARA, LEMOCOT, Berg Balance Scale, 10-Meter Walk Test, and Finger-to-nose Test. Findings. Participation was significantly lower in the wheelchair user subgroup. Also, for 29 activities out of 77, at least 15% of participants reported severely disrupted participation. Participation was correlated with upper and lower limbs coordination, walking ability, balance, disease severity, and fine dexterity (Spearman r = .41-0.85, p < .03). Implications. Results showed significant participation restrictions and suggest that interventions aiming to improve or compensate upper and lower limbs functions could help to decrease disease burden.

Optimizing treatment sequencing of chemotherapy for patients with rectal cancer: The KIR randomized phase II trial.

BACKGROUND: Randomized studies have shown low compliance to adjuvant chemotherapy in rectal cancer patients receiving preoperative chemotherapy and external beam radiation (CT/EBRT) with total mesorectal excision. We hypothesize that giving neoadjuvant CT before local treatment would improve CT compliance. METHODS: Between 2010-2017, 180 patients were randomized (2:1) to either Arm A (AA) with FOLFOX x6 cycles prior to high dose rate brachytherapy (HDRBT) and surgery plus adjuvant FOLFOX x6 cycles, or Arm B (AB), with neoadjuvant HDRBT with surgery and adjuvant FOLFOX x12 cycles. The primary endpoint was CT compliance to ≥85% of full-dose CT for the first six cycles. Secondary endpoints were ypT0N0, five-year disease free survival (DFS), local control and overall survival (OS). RESULTS: Patients were randomized to either AA (n = 120, median age (MA) 62 years) or AB (n = 60, MA 63 years). 175/180 patients completed HDRBT as planned (97.2%). In AA, two patients expired during CT; three patients post-randomization received short course EBRT because of progression under CT (n = 2, AA) or personal preference (n = 1, AB). ypT0N0 was 31% in AA and 28% in AB (p = 0.7). CT Compliance was 80% in AA and 53% in AB (p = 0.0002). Acute G3/G4 toxicity was 35.8% in AA and 27.6% in AB (p = 0.23). With a median follow-up of 48.5 months (IQR 33-72), the five-year DFS was 72.3% with AA and 68.3% with AB (p = 0.74), the five-year OS 83.8% for AA and 82.2% for AB (p = 0.53), and the five-year local recurrence was 6.3% for AA and 5.8% for AB (p = 0.71). CONCLUSION: We confirmed improved compliance to neoadjuvant CT in this study. Although there is no statistical difference in ypT0N0 rate, local recurrence, and DFS between the two arms, a trend towards favourable oncological outcomes is observed.

Development and validation of a disease severity index for ataxia of Charlevoix-Saguenay.

OBJECTIVE: To develop a disease-specific severity index for adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) (DSI-ARSACS) that considers the 3 components (pyramidal, cerebellar, neuropathic) of the disease, and to document its content validity, internal consistency, and construct validity. METHODS: The Beta DSI-ARSACS (17 items) was developed based on literature review and expert inputs and then administered to 26 participants. Items reduction was based on Cronbach α and desirable criteria. Performance measures were administered to assess the construct validity of the final version of the DSI-ARSACS. RESULTS: The final DSI-ARSACS have 8 items that can be easily performed during usual medical follow-up. The mean score was 19.6 ± 8.1 (range 6.0-35.5) and the Cronbach α was 0.912. The DSI-ARSACS score increased with disease stage and age (p ≤ 0.001) and was closely correlated with other measures assessing similar construct (9-Hole Peg Test, 10-Meter Walk Test, Scale for the Assessment and Rating of Ataxia, Berg Balance Scale, Barthel Index) (r s = 0.75-0.95, p < 0.01). A moderate but not significant correlation was found with the 6-Minute Walk test (r s = -0.611, p = 0.108). CONCLUSIONS: The DSI-ARSACS is a valid measure of disease severity for the adult ARSACS population that is able to distinguish between patients with different clinical profiles. Further documentation of metrologic properties is necessary, but these first results are promising.

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial.

IMPORTANCE: Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important. OBJECTIVE: To conduct a phase 2 study to evaluate the safety and feasibility of using magnetic resonance imaging (MRI) criteria to select patients with "good prognosis" rectal tumors for primary surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective nonrandomized phase 2 study at 12 high-volume colorectal surgery centers across Canada. From September 30, 2014, to October 21, 2016, a total of 82 patients were recruited for the study. Participants were patients newly diagnosed as having rectal cancer with MRI-predicted good prognosis rectal cancer. The MRI criteria for good prognosis tumors included distance to the mesorectal fascia greater than 1 mm; definite T2, T2/early T3, or definite T3 with less than 5 mm of extramural depth of invasion; and absent or equivocal extramural venous invasion. INTERVENTIONS: Patients with rectal cancer with MRI-predicted good prognosis tumors underwent primary surgery. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a positive circumferential resection margin (CRM) rate. Assuming a 10% baseline probability of a positive CRM, a sample size of 75 was estimated to yield a 95% CI of ±6.7%. RESULTS: Eighty-two patients (74% male) participated in the study. The median age at the time of surgery was 66 years (range, 37-89 years). Based on MRI, most tumors were midrectal (65% [n = 53]), T2/early T3 (60% [n = 49]), with no suspicious lymph nodes (63% [n = 52]). On final pathology, 91% (n = 75) of tumors were T2 or greater, 29% (n = 24) were node positive, and 59% (n = 48) were stage II or III. The positive CRM rate was 4 of 82 (4.9%; 95% CI, 0.2%-9.6%). CONCLUSIONS AND RELEVANCE: The use of MRI criteria to select patients with good prognosis rectal cancer for primary surgery results in a low rate of positive CRM and suggests that CRT may not be necessary for all patients with stage II and III rectal cancer. TRIAL REGISTRATION: ISRCTN.com identifier: ISRCTN05107772.

Radiation Therapy-Induced Dysfunction in Cardiovascular Implantable Electronic Devices.

PURPOSE: The prevalence of patients with cardiovascular implantable electronic devices (CIEDs) who receive radiation treatment for cancer is increasing. External beam radiation therapy (RT) can affect the electronic components. This study aimed to evaluate the incidence and predictors of new onset CIED dysfunction in patients treated with RT. METHODS AND MATERIALS: We retrospectively analyzed data from 230 patients with CIEDs who received radiation treatment at the Radiation Oncology Center of CHU de Québec - Université Laval between February 2007 and November 2013. The reviewed data included baseline characteristics, CIEDs, and RT treatment specifications. Patients with CIEDs were analyzed before, during, and at the end of radiation treatment. High- and low-energy photon or electron beam radiation from linear accelerators, orthovoltage machines, and high-dose rate brachytherapy delivery were used. Abnormal events could be one of the following: total or partial deprogramming of the CIED parameters, onset of new symptoms, or new arrhythmia. RESULTS: This study is based on one of the largest cohorts. A total of 18 events in 16 patients (7.8%) were recorded. Of the 18 events, 16 had at least part of the radiation treatment delivered with photo neutrons producing high-energy RT (neutron producing RT). Only 2 abnormal events occurred during non-neutron producing RT. Both the prescription dose and the dose estimated at the location of the pacemaker were correlated with the probability of an abnormal event (P = .0006 and P = .003, respectively). Among the 16 patients, clinical symptoms were noted in only 1 patient (6.3%). CONCLUSIONS: CIED malfunctions are relatively uncommon and do not seem to be life threatening. We recommend limiting the dose at the CIED and avoid neutron-producing RT to reduce the risk of CIED malfunction.

From motor performance to participation: a quantitative descriptive study in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

BACKGROUND: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a recessive neurological disorder with cerebellar, pyramidal and neuropathic features. Natural history data are urgently needed to increase trial readiness. This study aimed to describe the clinical phenotype including dexterity, coordination, strength, mobility, balance, disease severity, participation, and quality of life observed in adults with ARSACS homozygous for the c.8844delT mutation. METHODS: Cross-sectional study with comparisons between disease stages and with reference values. Outcome measures included Standardized Finger-to-Nose Test, Grip/pinch strength, LEMOCOT, Six-Minute Walk Test, 10-Meter Walk Test, Berg Balance Scale, Spastic Paraplegia Rating Scale, Scale for the Assessment and Rating of Ataxia, LIFE-H, and SF-12. RESULTS: Twenty-eight participants were recruited with a mean age of 38.1 years. The majority presented with lower limb coordination and fine dexterity scores below three standard deviations compare to reference values, scored under predicted values for mobility measures and were at increased risk of fall. Participants at an earlier disease stage performed better than the others, but individual variability was observed. CONCLUSIONS: Results showed overall impaired motor performances and, even in a genetically homogeneous ARSACS population, an individual variability within disease stages. This study lays the foundation for a longitudinal study using quantified measurements.

An exploratory natural history of ataxia of Charlevoix-Saguenay: A 2-year follow-up.

OBJECTIVE: To document the decline of upper and lower limb functions, mobility, and independence in daily living activities in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) over a 2-year period. METHODS: An exploratory longitudinal design was used. Nineteen participants were assessed on 2 occasions 2 years apart. Assessments included the Standardized Finger Nose Test, Nine-Hole Peg Test, Lower Extremity Motor Coordination Test, Berg Balance Scale, 10-m walk test (10mWT), 6-minute walk test (6MWT), Scale for the Assessment and Rating of Ataxia (SARA), and Barthel Index. RESULTS: A significant decline was observed between baseline and follow-up for lower limb coordination, balance, walking abilities (10mWT and 6MWT), and overall disease severity (SARA). All differences were beyond measurement error documented in ARSACS. Results showed no significant decline for upper limb coordination and fine dexterity performance. CONCLUSION: Although ARSACS is a slow, progressive disease, results showed that mobility, balance, and lower limb performance significantly decreased over the 2-year period and that selected outcome measures were able to capture this decline beyond measurement errors.

Assessing mobility and balance in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay population: Validity and reliability of four outcome measures.

OBJECTIVE: To assess the construct validity of the 10-Meter Walk Test (10mWT), Six-Minute Walk Test (6MWT), Berg Balance Scale (BERG), and Timed Up and Go (TUG) in adults with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), in addition to the interrater reliability of the 10mWT and 6MWT. METHODS: Reliability was determined using the intraclass correlation coefficient (ICC). Validity was determined first by correlating the 10mWT, 6MWT, BERG, and TUG with participant's age, lower limb coordination, and disease severity, and then by assessing their capacity to distinguish between participants based on sex and disease stages. RESULTS: Interrater reliability of the 10mWT at both comfortable and maximum speed as well as the 6MWT is excellent (ICC = 0.97-0.99). Construct validity of the four tests was confirmed, as showed by the high correlations with age, lower limb coordination, and overall disease severity (ρ = 0.64-0.97). CONCLUSIONS: The four tests assessed for their metrological properties in this study showed to be valid instruments to use in the ARSACS population. The 10mWT and 6MWT are also highly reliable. BERG and TUG reliability will need to be assess in a future study.

Validity and Reliability of Outcome Measures Assessing Dexterity, Coordination, and Upper Limb Strength in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

OBJECTIVE: To document in adults affected by autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) the intra- and interrater reliability, standard error of measurement, agreement, minimal detectable change, and construct validity of the 9-Hole Peg Test (NHPT), the Standardized Finger-to-Nose Test (SFNT), and grip strength. DESIGN: Metrologic study. SETTING: Neuromuscular rehabilitation clinic. PARTICIPANTS: Genetically confirmed adult patients with ARSACS (N=42; 21 women; mean age, 38.6y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Intra- and interrater reliability was determined using the intraclass correlation coefficient (ICC). Construct validity was determined by assessing the capacity of the NHPT, the SFNT, and grip strength to distinguish between participants based on sex, mobility stages, and age groups, and on performance on the Archimedes spiral and fast alternating hand movements tests. RESULTS: All 3 tests have shown excellent reliability (ICC=.90-.98). However, the limit of agreement was influenced by the participant's performance on the NHPT, and the minimal detectable change was very different for both hands (right=9.7 vs left=28.0). Construct validity was confirmed for the SFNT and NHPT, but it was not demonstrated for grip strength. CONCLUSIONS: Given the metrologic properties assessed in this study, the SFNT is an excellent measure to assess upper limb coordination, whereas the NHPT must be used with caution. The grip strength is reliable but does not seem to reflect disease severity.

Validity and reliability of the LEMOCOT in the adult ARSACS population: A measure of lower limb coordination.

OBJECTIVE: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neuromuscular disease leading to several impairments, including decrease of lower limb coordination. The Lower Extremity Motor Coordination Test (LEMOCOT) is an outcome measure recently developed for stroke population. The aim of this study was to document: 1) intra- and interrater reliability; 2) the standard error of measurement and minimal detectable change; and 3) the construct validity of the measurements obtained with the LEMOCOT in the adult ARSACS population. RESULTS: The LEMOCOT has shown a good intra- and interrater reliability with an intraclass correlation coefficient ranging from 0.92 to 0.97 for both dominant and non-dominant side. The construct validity (hypothesis testing) is satisfying where LEMOCOT's score negatively correlated with participants' age (r=-0.74) and the score of the Scale for the Assessment and Rating of Ataxia (r=-0.86) and positively correlated with the balance and mobility tests (r=0.82 with the Berg Balance Scale, r=0.61 with the Six-Minute Walk Test, r=0.57 with the 10-Meter Walk Test). The LEMOCOT was also able to distinguish between patients according to disease stages. CONCLUSION: The LEMOCOT is a valid and reliable tool to assess lower limb coordination in the ARSACS population for whom the lack of coordination is a common symptom.

Radiotherapy-Induced Cardiac Implantable Electronic Device Dysfunction in Patients With Cancer.

Radiotherapy can affect the electronic components of a cardiac implantable electronic device (CIED) resulting in malfunction and/or damage. We sought to assess the incidence, predictors, and clinical impact of CIED dysfunction (CIED-D) after radiotherapy for cancer treatment. Clinical characteristics, cancer, different types of CIEDs, and radiation dose were evaluated. The investigation identified 230 patients, mean age 78 ± 8 years and 70% were men. A total of 199 patients had pacemakers (59% dual chamber), 21 (9%) cardioverter-defibrillators, and 10 (4%) resynchronizators or defibrillators. The left pectoral (n = 192, 83%) was the most common CIED location. Sixteen patients (7%) experienced 18 events of CIED-D after radiotherapy. Reset to backup pacing mode was the most common encountered dysfunction, and only 1 (6%) patient of those with CIED-D experienced symptoms of atrioventricular dyssynchrony. Those who had CIED-D tended to have a shorter device age at the time of radiotherapy compared to those who did not (2.5 ± 1.5 vs 3.8 ± 3.4 years, p = 0.09). The total dose prescribed to the tumor was significantly greater among those who had CIED-D (66 ± 30 vs 42 ± 23 Gy, p <0.0001). Multivariate logistic regression analysis identified the total dose prescribed to the tumor as the only independent predictor for CIED-D (odds ratio 1.19 for each increase in 5 Gy, 95% confidence interval 1.08 to 1.31, p = 0.0005). In conclusion, in this large population of patients with CIEDs undergoing radiotherapy for cancer treatment, the occurrence of newly diagnosed CIED-D was 7%, and the reset to backup pacing mode was the most common encountered dysfunction. The total dose prescribed to the tumor was a predictor of CIED-D. Importantly, although the unpredictability of CIEDs under radiotherapy is still an issue, none of our patients experienced significant symptoms, life-threatening arrhythmias, or conduction disorders.

Long-term quality of life in early-stage non-small cell lung cancer patients treated with robotic stereotactic ablative radiation therapy.

PURPOSE: The purpose of this study was to prospectively evaluate the quality of life (QoL) and pulmonary function of patients with early-stage non-small cell lung cancer treated with robotic stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: Eligible patients all had histologically confirmed stage I non-small cell lung cancer and were not surgical candidates because of poor pulmonary function, comorbidities, or refusal of surgery. SABR was delivered at a median dose of 60 Gy in 3 fractions for peripheral tumors and 50 Gy in 4 or 5 fractions for central tumors. QoL was scored using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) and Lung Cancer-13 questionnaires. Pulmonary function tests (PFTs) included forced expiratory volume in 1 second (FEV1) and lung diffusion capacity. Changes over time in QoL scores and PFTs were tested with nonparametric tests for longitudinal data. Local control, survival, and toxicities are also presented. RESULTS: From January 2010 to May 2013, 45 patients were enrolled. Median follow-up was 41 months. QLQ-C30 mean baseline scores for global QoL and physical functioning were 66 ± 20% and 73 ± 22%. Multilevel analyses showed no statistically and clinically significant (10-point change) deterioration in any of the QoL scores after SABR. Mean baseline FEV1 was 1.39 ± 0.51 L, and mean lung diffusion capacity was 63 ± 25% of predicted. We saw no significant change in PFTs at any time point. At 3 years, local control, disease-free survival, and overall survival were, respectively, 94%, 67%, and 75%. CONCLUSIONS: In nonsurgical patients with multiple comorbidities, lung SABR achieves long-term local control while maintaining QoL and pulmonary function.

Excellent Cancer Outcomes Following Patient-adapted Robotic Lung SBRT But a Case for Caution in Idiopathic Pulmonary Fibrosis.

The aim of this study is to report outcomes and prognostic factors for early stage non-small cell lung cancer treated with patient-adapted Cyberknife stereotactic body radiotherapy. A retrospective analysis of 150 patients with T1-2N0 non-small cell lung cancer treated with stereotactic body radiotherapy was conducted. An algorithm based on tumor and patient's characteristics was used to orient patients towards soft tissue (Xsight Lung), fiducials or adjacent bone (Xsight Spine) tracking. Median biological effective dose without correction for tissue inhomogeneities was 180 Gy10 for peripheral tumors and 113 Gy10 for central tumors. Median follow-up was 22 months. Actuarial 2 years local control, overall survival and disease-specific survival were respectively 96%, 87% and 95%. Every 1 cm increase in tumor diameter was associated with a relative risk for regional or distant relapse of 2 (95%CI = 1.2-3.6, p = 0.009). With doses ≥132 Gy10 and <132 Gy10, local control was 98% vs. 82% (p = 0.07), disease-specific survival 97% vs. 78% (p = 0.02) and overall survival 93% vs. 76% (p = 0.01), respectively. Better disease-specific survival and a trend for better overall survival was observed for peripheral vs. central tumors (96% vs. 79%, p = 0.05 and 92% vs. 74%, p = 0.08, respectively). A higher Charlson comordibity score (≥4) predicted lower overall survival (79% vs. 98%, p = 0.01). Toxicities included 3 patients with idiopathic pulmonary fibrosis who developed grade 5 pneumonitis and 2 patients with grade 3 pneumonitis. We therefore report excellent local control and disease-specific survival following patient-adapted Cyberknife lung stereotactic body radiotherapy. Although toxicities were in general minimal, patients with pulmonary fibrosis might be at greater risk of severe complications. Small size, peripheral location, dose ≥ 132 Gy10 and a low Charlson co-morbidity score seem to be associated with better outcomes.

The Virtual Peg Insertion Test as an assessment of upper limb coordination in ARSACS patients: a pilot study.

OBJECTIVE: This paper introduces a novel assessment tool to provide clinicians with quantitative and more objective measures of upper limb coordination in patients suffering from Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS). The Virtual Peg Insertion Test (VPIT) involves manipulating an instrumented handle in order to move nine pegs into nine holes displayed in a virtual environment. The main outcome measures were the number of zero-crossings of the hand acceleration vector, as a measure of movement coordination and the total time required to complete the insertion of the nine pegs, as a measure of overall upper limb performance. RESULTS: 8\9 patients with ARSACS were able to complete five repetitions with the VPIT. Patients were found to be significantly less coordinated and slower than age-matched healthy subjects (p<0.01). Performance of ARSACS patients was positively correlated with the Nine-Hole Peg Test (r=0.85, p<0.01) and with age (r=0.93, p<0.01), indicative of the degenerative nature of the disease. CONCLUSION(S): This study presents preliminary results on the use of a robotics and virtual reality assessment tool with ARSACS patients. Results highlight its potential to assess impaired coordination and monitor its progression over time.

Volumetric image guidance using carina vs spine as registration landmarks for conventionally fractionated lung radiotherapy.

PURPOSE: To 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. METHODS AND MATERIALS: For 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. RESULTS: Spine 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. CONCLUSION: Frequent 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.

Functional avoidance of lung in plan optimization with an aperture-based inverse planning system.

PURPOSE: To implement SPECT-based optimization in an anatomy-based aperture inverse planning system for the functional avoidance of lung in thoracic irradiation. MATERIAL AND METHODS: SPECT information has been introduced as a voxel-by-voxel modulation of lung importance factors proportionally to the local perfusion count. Fifteen cases of lung cancer have been retrospectively analyzed by generating angle-optimized non-coplanar plans, comparing a purely anatomical approach and our functional approach. Planning target volume coverage and lung sparing have been compared. Statistical significance was assessed by a Wilcoxon matched pairs test. RESULTS: For similar target coverage, perfusion-weighted volume receiving 10 Gy was reduced by a median of 2.2% (p=0.022) and mean perfusion-weighted lung dose, by a median of 0.9 Gy (p=0.001). A separate analysis of patients with localized or non-uniform hypoperfusion could not show which would benefit more from SPECT-based treatment planning. Redirection of dose sometimes created overdosage regions in the target volume. Plans consisted of a similar number of segments and monitor units. CONCLUSIONS: Angle optimization and SPECT-based modulation of importance factors allowed for functional avoidance of the lung while preserving target coverage. The technique could be also applied to implement PET-based modulation inside the target volume, leading to a safer dose escalation.

Dose escalation in the radiotherapy of non-small-cell lung cancer with aperture-based intensity modulation and photon beam energy optimization for non-preselected patients.

PURPOSE: To verify the potential of aperture-based intensity-modulated radiotherapy (AB-IMRT) to realize dose escalation plans for non-preselected non-small-cell lung cancer (NSCLC) patients, using photon beam energy optimization. METHODS AND MATERIALS: Seven cases of NSCLC were retrospectively studied. Clinical reference plans were made at 60 Gy by an experienced dosimetrist. Dose escalation was applied to PTV2, a subvolume within the main PTV1. Escalation plans were optimized by considering beam angles (table and gantry), energy (6 and 23 MV) and weights, for an increasing dose to the PTV2, starting from 66 Gy and keeping 30 fractions. RESULTS: In five cases, doses over 78 Gy could be achieved before exceeding organs at risk (OARs) standard tolerance. Peripheral overdosages, as well as lung and spinal cord tolerance doses, limited escalation. Means+/-SD V(95%) parameters were (97.3+/-0.9)% for PTV1s and (96.7+/-2.2)% for PTV2s. Doses to OARs were also maintained at acceptable levels. Optimized plans made use of both low- and high-energy beams and had a similar number of monitor units compared to the 60 Gy clinical plans. CONCLUSIONS: The AB-IMRT system can successfully realize dose escalation for a sizeable number of cases. Plans produced contained few large segments, and are applicable to a wide range of tumor volumes and locations.