Intensity-modulated Radiation Therapy for Anal Cancer: Results From a Multi-Institutional Retrospective Cohort Study.

OBJECTIVES: To assess toxicity and efficacy of intensity-modulated radiation therapy (IMRT) for anal cancer. METHODS: Records of 152 patients were reviewed retrospectively from multiple institutions. Data on disease control and toxicity were collected as well as patient and treatment characteristics. Acute (<6 mo) and late (≥6 mo) severe toxicity (grade ≥3) were graded. Four patients were excluded due to the presence of metastatic disease or stage TX. Late toxicity data were available for 120 patients. RESULTS: Median cumulative IMRT dose was 51.25 Gy (median, 28 fractions). All but 2 patients received chemotherapy. With median follow-up of 26.8 months, local control at 3 years was 87%, worse for patients with T3-T4 than T1-T2 disease on univariate analysis (79% vs. 90%; P=0.04). Regional control, distant control, and overall survival were 97%, 91%, and 87%, respectively, at 3 years. Nodal status was associated with regional control, distant control, and overall survival (P<0.01 for each). Most common severe acute toxicity was hematologic (41%), skin (20%), and gastrointestinal tract (11%). Two grade 5 toxicities occurred (hematologic and gastrointestinal tract). Severe late toxicity affected skin (1%) and gastrointestinal tract (3%). CONCLUSIONS: IMRT with chemotherapy resulted in excellent local control. Although T stage predicted worse local control, most T3-T4 disease was controlled with IMRT. Nodal status predicted regional and distant control and overall survival. Severe toxicity was acceptable.

Stereotactic body radiation therapy (SBRT) for lung malignancies: preliminary toxicity results using a flattening filter-free linear accelerator operating at 2400 monitor units per minute.

BACKGROUND: Flattening filter-free (FFF) linear accelerators (linacs) are capable of delivering dose rates more than 4-times higher than conventional linacs during SBRT treatments, causing some to speculate whether the higher dose rate leads to increased toxicity owing to radiobiological dose rate effects. Despite wide clinical use of this emerging technology, clinical toxicity data for FFF SBRT are lacking. In this retrospective study, we report the acute and late toxicities observed in our lung radiosurgery experience using a FFF linac operating at 2400 MU/min. METHODS: We reviewed all flattening filter-free (FFF) lung SBRT cases treated at our institution from August 2010 through July 2012. Patients were eligible for inclusion if they had at least one clinical assessment at least 30 days following SBRT. Pulmonary, cardiac, dermatologic, neurologic, and gastrointestinal treatment related toxicities were scored according to CTCAE version 4.0. Toxicity observed within 90 days of SBRT was categorized as acute, whereas toxicity observed more than 90 days from SBRT was categorized as late. Factors thought to influence risk of toxicity were examined to assess relationship to grade > =2 toxicity. RESULTS: Sixty-four patients with >30 day follow up were eligible for inclusion. All patients were treated using 10 MV unflattened photons beams with intensity modulated radiation therapy (IMRT) inverse planning. Median SBRT dose was 48 Gy in 4 fractions (range: 30-60 Gy in 3-5 fractions). Six patients (9%) experienced > = grade 2 acute pulmonary toxicity; no non-pulmonary acute toxicities were observed. In a subset of 49 patients with greater than 90 day follow up (median 11.5 months), 11 pulmonary and three nerve related grade > =2 late toxicities were recorded. Pulmonary toxicities comprised six grade 2, three grade 3, and one each grade 4 and 5 events. Nerve related events were rare and included two cases of grade 2 chest wall pain and one grade 3 brachial plexopathy which spontaneously resolved. No grade > =2 late gastrointestinal, skin, or cardiac toxicities were observed. Tumor size, biologically effective dose (BED10, assuming α/ß of 10), and tumor location (central vs peripheral) were not significantly associated with grade > =2 toxicity. CONCLUSIONS: In this early clinical experience, lung SBRT using a FFF linac operating at 2400 MU/min yields minimal acute toxicity. Preliminary results of late treatment related toxicity suggest reasonable rates of grade > =2 toxicities. Further assessment of late effects and confirmation of the clinical efficacy of FFF SBRT is warranted.

Effects of flattening filter-free and volumetric-modulated arc therapy delivery on treatment efficiency.

Flattening filter-free (FFF) beams are available on an increasing number of commercial linear accelerators. FFF beams have higher dose rates than flattened beams of equivalent energy which can lead to increased efficiency of treatment delivery, especially in conjunction with increased FFF beam energy and arc-based delivery configurations. The purpose of this study is to quantify and assess the implications of improved treatment efficiency for several FFF delivery options on common types of linac applicable radiotherapy. Eleven characteristic cases representative of a variety of clinical treatment sites and prescription doses were selected from our patient population. Treatment plans were generated for a Varian TrueBeam linear accelerator. For each case, a reference plan was created using DMLC IMRT with 6MV flat beams. From the same initial objectives, plans were generated using DMLC IMRT and volumetric-modulated arc therapy (VMAT) with 6 MV FFF and 10 MV FFF beams (max. dose rates of 1400 and 2400 MU/min, respectively). The plans were delivered to a phantom; beam-on time, total treatment delivery time, monitor units (MUs), and integral dose were recorded. For plans with low dose fractionations (1.8-2.0 & 3.85 Gy/fraction), mean beam-on time difference between reference plan and most efficient FFF plan was 0.56 min (41.09% decrease); mean treatment delivery time difference between the reference plan and most efficient FFF plan was 1.54 min (range: 0.31-3.56 min), a relative improvement of 46.1% (range: 29.2%-59.2%). For plans with high dose fractionations (16-20 Gy/fraction), mean beam-on time difference was 6.79 min (74.9% decrease); mean treatment delivery time difference was 8.99 min (range: 5.40-13.05 min), a relative improvement of 71.1% (range: 53.4%- 82.4%). 10 MV FFF VMAT beams generated the most efficient plan, except in the spine SBRT case. The distribution of monitor unit counts did not vary by plan type. In cases where respiratory motion management would be applicable, 10 MV FFF DMLC IMRT reduced beam-on time/field to less than 12 sec. FFF beams significantly reduced treatment delivery time. For radiosurgical doses, the efficiency improvement for FFF beams was clinically significant. For conventional fractionation, a large improvement in relative treatment delivery time was observed, but the absolute time savings were not likely to be of clinical value. In cases that benefit from respiratory motion management, beam-on/field was reduced to a time for which most patients can comfortably maintain deep inspiratory breath hold.

Flattening filter-free linac improves treatment delivery efficiency in stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) employs precision target tracking and image-guidance techniques to deliver ablative doses of radiation to localized malignancies; however, treatment with conventional photon beams requires lengthy treatment and immobilization times. The use of flattening filter-free (FFF) beams operating at higher dose rates can shorten beam-on time, and we hypothesize that it will shorten overall treatment delivery time. A total of 111 lung and liver SBRT cases treated at our institution from July 2008 to July 2011 were reviewed and 99 cases with complete data were identified. Treatment delivery times for cases treated with a FFF linac versus a conventional dose rate linac were compared. The frequency and type of intrafraction image guidance was also collected and compared between groups. Three hundred and ninety-one individual SBRT fractions from 99 treatment plans were examined; 36 plans were treated with a FFF linac. In the FFF cohort, the mean (± standard deviation) treatment time (time elapsed from beam-on until treatment end) and patient's immobilization time (time from first alignment image until treatment end) was 11.44 (± 6.3) and 21.08 (± 6.8) minutes compared to 32.94 (± 14.8) and 47.05 (± 17.6) minutes for the conventional cohort (p < 0.01 for all values). Intrafraction-computed tomography (CT) was used more often in the conventional cohort (84% vs. 25%; p < 0.05), but use of orthogonal X-ray imaging remained the same (16% vs. 19%). For lung and liver SBRT, a FFF linac reduces treatment and immobilization time by more than 50% compared to a conventional linac. In addition, treatment with a FFF linac is associated with less physician-ordered image guidance, which contributes to further improvement in treatment delivery efficiency.

Plan quality and treatment planning technique for single isocenter cranial radiosurgery with volumetric modulated arc therapy.

PURPOSE: To demonstrate plan quality and provide a practical, systematic approach to the treatment planning technique for single isocenter cranial radiosurgery with volumetric modulated arc therapy (VMAT; RapidArc, Varian Medical systems, Palo Alto, CA). METHODS AND MATERIALS: Fifteen patients with 1 or more brain metastases underwent single isocenter VMAT radiosurgery. All plans were normalized to deliver 100% of the prescription dose to 99%-100% of the target volume. All targets per plan were treated to the same dose. Plans were created with dose control tuning structures surrounding targets to maximize conformity and dose gradient. Plan quality was evaluated by calculation of conformity index (CI = 100% isodose volume/target volume) and homogeneity index (HI = maximum dose/prescription dose) scores for each target and a Paddick gradient index (GI = 50% isodose volume/100% isodose volume) score for each plan. RESULTS: The median number of targets per patient was 2 (range, 1-5). The median number of non-coplanar arcs utilized per plan was 2 (range, 1- 4). Single target plans were created with 1 or 2 non-coplanar arcs while multitarget plans utilized 2 to 4 non-coplanar arcs. Prescription doses ranged from 5-16 Gy in 1-5 fractions. The mean conformity index was 1.12 (± SD, 0.13) and the mean HI was 1.44 (± SD, 0.11) for all targets. The mean GI per plan was 3.34 (± SD, 0.42). CONCLUSIONS: We have outlined a practical approach to cranial radiosurgery treatment planning using the single isocenter VMAT platform. One or 2 arc single isocenter plans are often adequate for treatment of single targets, while 2-4 arcs may be more advantageous for multiple targets. Given the high plan quality and extreme clinical efficiency, this single isocenter VMAT approach will continue to become more prevalent for linac-based radiosurgical treatment of 1 or more intracranial targets and will likely replace multiple isocenter techniques.

Dosimetric analysis of imaging changes following pulmonary stereotactic body radiation therapy.

INTRODUCTION: The aim of this study was to determine whether late patterns of pulmonary fibrosis are related to specific radiation doses administered during thoracic stereotactic body radiation therapy (SBRT). METHODS: The records of all patients treated with SBRT for either pulmonary metastases or inoperable primary lung tumours at the University of Alabama at Birmingham from November 2005 to July 2008 were reviewed. Patients selected for analysis had diagnostic chest computed tomography (CT) scans acquired at least 180 days after completion of therapy. CT scans acquired at follow-up were co-registered with the original treatment planning CT scans for 12 eligible patients (17 lesions), and late-occurring pulmonary imaging abnormalities (IAs) were contoured. Dosimetric parameters analysed include D(80) , D(90) , V(18) and V(prescription dose) of the IA and V(14) and V(18) of the lung. RESULTS: Late pulmonary IAs were identified in 11 treated areas from nine patients. Late IAs could not be identified in six treated areas from three patients secondary to emphysema, tumour progression and severe atelectasis, respectively. The mean doses to 80% (D(80) ) and 90% (D(90) ) of the IAs were 18.4 and 14.5 Gy, respectively (ranges: 5.6-27.8 and 3.3-22.4 Gy). On average, 79.4% (range: 45.6-97.5%) of the IA received at least 18 Gy, while an average of 19.3% (range: 0.2-42.2%) received the prescription dose. On average, only 4.2% (range: 1.1-7.8%) of the lungs received 18 Gy. CONCLUSION: Imaging abnormalities consistent with pulmonary fibrosis are common after SBRT and are well approximated by the 18 Gy isodose distribution. The clinical ramification of these findings should be evaluated in future studies.

Improved clinical efficiency in CNS stereotactic radiosurgery using a flattening filter free linear accelerator.

Linear accelerator (linac) based CNS stereotactic radiosurgery (SRS) requires significant time resources. We hypothesized that CNS SRS using a flattening filter free (FFF) linac would reduce treatment time and improve clinical efficiency. A FFF linac was recently commissioned for CNS radiosurgery at the University of Alabama at Birmingham. The efficiency of this linac for CNS SRS was retrospectively reviewed. Beam on time (BOT), time in room (TIR), and clinical dose rate (CDR) were calculated using an integrated treatment planning, record, and verification software platform and are proposed as surrogates for treatment efficiency. Twenty-seven eligible CNS SRS cases consisting of 1-5 fractions of 5 Gy or more per fraction were reviewed. Mean BOT was 1:21 (minutes:seconds; range: 00:36-2:52) and mean TIR was 10:42 (minutes:seconds; range: 6:05-22:56). The mean CDR was 1820 MU/ min (range: 872-2396). On regression analysis the number of alignment images, treatment arcs, targets, monitor units, and presence of intra-fraction imaging were factors significantly (p < 0.05) associated with prolonged TIR. Use of FFF mode in CNS SRS more than triples the CDR and results in shortened BOT and TIR compared to treatment at conventional dose rates. Reduction in clinical treatment times may translate to better target localization due to reduced opportunity for intrafraction motion. Linac-based CNS SRS can be completed in a normal time slot with a high output FFF linac.