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Background: Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity., Methods: Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain., Results: At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P = 0.029., Conclusion: Modern radiation therapy can significantly improve long-term PRO., Trial Registration: Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively., (© 2021. The Author(s).)

Purpose: To evaluate alterations in pulmonary function indices after helical tomotherapy and explore potential associations with biologically corrected dosimetric parameters., Patients and Methods: In 64 patients with inoperable locally advanced non-small cell lung cancer, pulmonary function tests before and within 6 months after radiotherapy were evaluated retrospectively. In the case of concurrent chemotherapy a total dose of 67.2 Gy was delivered, otherwise 70.5 Gy was provided. In 44 patients, late pulmonary function changes (≥6 months after radiotherapy) could also be assessed., Results: In the entire patient group, there were significant declines in forced expiratory volume in 1s (FEV 1 ) (average change -4.1% predicted; P = 0.007), in forced vital capacity (FVC) (-4.9% predicted; P = 0.002), total lung capacity (TLC) (-5.8% predicted; P = 0.0016) and DL CO (diffusing capacity of the lung for carbon monoxide corrected for hemoglobin level) (-8.6% predicted; P < 0.001) during the first 6 months. Corresponding FEV 1 , FVC, TLC and DL CO declines in the subgroup with late measurements (after 11.3 months on average) were -5.7, -7.4, -7.0, -9.8% predicted. A multivariate analysis including V 5   Gy , V 10   Gy , V 20   Gy , V 40   Gy , V 60   Gy , mean lung dose (MLD), gross tumor volume (GTV) and planning target volume (PTV) as potential covariates showed that GTV was the most consistent contributor, being significant for ∆FEV 1 (P = 0.003), ∆FVC (P = 0.003), ∆TLC (P = 0.001) and ∆DL CO (P = 0.01). V 5   Gy or V 10   Gy did not contribute to any of the lung function changes., Conclusions: The decline in pulmonary function indices after helical tomotherapy was of similar magnitude to that observed in studies reporting the effect of conformal radiotherapy on lung function. Diffusion capacity was the parameter showing the largest decrease following radiation therapy as compared to baseline and correlated with gross tumor volume. None of the alterations in pulmonary function tests were associated with the lung volume receiving low-dose radiation.

Background: A 2-level factorial pilot study was conducted in 2007 just before starting a randomized clinical trial comparing tomotherapy and conventional radiotherapy (CR) to reduce cardiac and pulmonary adverse effects in breast cancer, considering tumor laterality (left/right), target volume (with/without nodal irradiation), surgery (tumorectomy/mastectomy), and patient position (prone/supine). The study was revisited using a penalty score based on the recently developed mean absolute dose deviation (MADD)., Methods: Eight patients with a unique combination of laterality, nodal coverage, and surgery underwent dual tomotherapy and CR treatment planning in both prone and supine positions, providing 32 distinct combinations. The penalty score was applied using the weighted sum of the MADDs. The Lenth method for unreplicated 2-level factorial design was used in the analysis., Results: The Lenth analysis identified nodal irradiation as the active main effect penalizing the dosimetry by 1.14 Gy (P = 0.001). Other significant effects were left laterality (0.94 Gy), mastectomy (0.61 Gy), and interactions between left mastectomy (0.89 Gy) and prone mastectomy (0.71 Gy), with P-values between 0.005 and 0.05. Tomotherapy provided a small reduction in penalty (reduction of 0.54 Gy) through interaction with nodal irradiation (P = 0.080). Some effects approached significance with P-values > 0.05 and ≤ 0.10 for interactions of prone × mastectomy × left (0.60 Gy), nodal irradiation × mastectomy (0.59 Gy), and prone × left (0.55 Gy) and the main effect prone (0.52 Gy)., Conclusions: The historical dosimetric analysis previously revealed the feasibility of tomotherapy, but a conclusion could not be made. The MADD-based score is promising, and a new analysis highlights the impact of factors and hierarchy of priorities that need to be addressed if major gains are to be attained.

Background: The diagnosis and treatment of head and neck carcinoma of unknown primary (CUP) have changed with the introduction of fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT and intensity-modulated radiotherapy (IMRT), with potential implications for outcome., Methods: We conducted a retrospective analysis of 80 patients with head and neck CUP who were PET-staged and treated with curative intention using IMRT between 2006 and 2016 in the Netherlands Cancer Institute. Patient, tumor, and treatment demographics were recorded and oncologic outcomes were analyzed., Results: Local control was 100% in mucosal irradiated patients. Regional control was 90%. Ten patients developed distant metastases, which were associated with N3, extracapsular extension (ECE) and lower neck positive lymph nodes. Overall survival (OS) at 5 years was 62% and disease-specific survival was 78%. ECE, N3 neck, multiple levels of positive lymph nodes, and positive lymph nodes in the lower neck were associated with worse prognosis., Conclusion: Locoregional outcome of head and neck CUP managed with modern techniques is good. Future research needs to focus on reducing toxicity and patients prone for distant metastasis., (© 2017 Wiley Periodicals, Inc.)

Background and Purpose: Dynamic Wave Arc (DWA) is a system-specific noncoplanar arc technique that combines synchronized gantry-ring rotation with D-MLC optimization. This paper presents the clinical workflow, quality assurance program, and reports the geometric and dosimetric results of the first patient cohort treated with DWA., Methods and Materials: The RayStation TPS was clinically integrated on the Vero SBRT platform for DWA treatments. The first 15 patients treated with DWA represent a broad range of treatment sites: breast boost, prostate, lung SBRT and bone metastases, which allowed us to explore the potentials and assess the limitations of the current DWA site-specific template solution. For the DWA verification a variety of QA equipment was used, from 3D diode array to an anthropomorphic end-to-end phantom. The geometric accuracy of each arc was verified with an independent orthogonal fluoroscopy method., Results: The average beam-on delivery time was 3min, ranging from 1.22min to 8.82min. All patient QAs passed our institutional clinical criteria of gamma index. For both EBT3 film and Delta4 measurements, DWA planned versus delivered dose distributions presented an average agreement above 97%. An overall mean gantry-ring geometric deviation of -0.03°±0.46° and 0.18°±0.26° was obtained, respectively., Conclusion: For the first time, DWA has been translated into the clinic and used to treat various treatment sides. DWA has been successfully added to the noncoplanar rotational IMRT techniques arsenal, allowing additional flexibility in dose shaping while preserving dosimetrically robust delivery., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Dynamic Wave Arc (DWA) is a clinical approach designed to maximize the versatility of Vero SBRT system by synchronizing the gantry-ring noncoplanar movement with D-MLC optimization. The purpose of this study was to verify the delivery accuracy of DWA approach and to evaluate the potential dosimetric benefits., Methods: DWA is an extended form of VMAT with a continuous varying ring position. The main difference in the optimization modules of VMAT and DWA is during the angular spacing, where the DWA algorithm does not consider the gantry spacing, but only the Euclidian norm of the ring and gantry angle. A preclinical version of RayStation v4.6 (RaySearch Laboratories, Sweden) was used to create patient specific wave arc trajectories for 31 patients with various anatomical tumor regions (prostate, oligometatstatic cases, centrally-located non-small cell lung cancer (NSCLC) and locally advanced pancreatic cancer-LAPC). DWA was benchmarked against the current clinical approaches and coplanar VMAT. Each plan was evaluated with regards to dose distribution, modulation complexity (MCS), monitor units and treatment time efficiency. The delivery accuracy was evaluated using a 2D diode array that takes in consideration the multi-dimensionality of DWA during dose reconstruction., Results: In centrally-located NSCLC cases, DWA improved the low dose spillage with 20 %, while the target coverage was increased with 17 % compared to 3D CRT. The structures that significantly benefited from using DWA were proximal bronchus and esophagus, with the maximal dose being reduced by 17 % and 24 %, respectively. For prostate and LAPC, neither technique seemed clearly superior to the other; however, DWA reduced with more than 65 % of the delivery time over IMRT. A steeper dose gradient outside the target was observed for all treatment sites (p < 0.01) with DWA. Except the oligometastatic cases, where the DWA-MCSs indicate a higher modulation, both DWA and VMAT modalities provide plans of similar complexity. The average ɣ (3 % /3 mm) passing rate for DWA plans was 99.2 ± 1 % (range from 96.8 to 100 %)., Conclusions: DWA proven to be a fully functional treatment technique, allowing additional flexibility in dose shaping, while preserving dosimetrically robust delivery and treatment times comparable with coplanar VMAT.

Purpose: To investigate the feasibility of a novel dedicated treatment planning solution, to automatically target multiple brain metastases with a single isocenter and multiple inversely-optimized dynamic conformal arcs (DCA), and to benchmark it against the well-established multiple isocenter DCA (MIDCA) and volumetric modulated arc therapy (VMAT) approaches., Material and Methods: Ten previously treated patients were randomly selected, each representing a variable number of lesions ranging between 1 to 8. The original MIDCA treatments were replanned with both VMAT and the novel brain metastases tool. The plans were compared by means of Paddick conformity (CI) and gradient index (GI), and the volumes receiving 10 Gy (V10) and 12 Gy (V12)., Results: The brain metastases software tool generated plans with similar CI (0.65 ± 0.08) as both established treatment techniques while improving the gradient (mean GI = 3.9 ± 1.4). The normal tissue exposure in terms of V10 (48.5 ± 35.9 cc) and V12 (36.3 ± 27.1 cc) compared similarly to the MIDCA technique and surpassed VMAT plans., Conclusions: The automated brain metastases planning algorithm software is an optimization of DCA radiosurgery by increasing delivery efficiency to the level of VMAT approaches. Improving dose gradients and normal tissue sparing over VMAT, revives DCA as the paradigm for linac-based stereotactic radiosurgery of multiple brain metastases.

Purpose: The purpose of this study was to define an independent verification method based on on-board orthogonal fluoroscopy to determine the geometric accuracy of synchronized gantry-ring (G/R) rotations during dynamic wave arc (DWA) delivery available on the Vero system., Methods and Materials: A verification method for DWA was developed to calculate O-ring-gantry (G/R) positional information from ball-bearing positions retrieved from fluoroscopic images of a cubic phantom acquired during DWA delivery. Different noncoplanar trajectories were generated in order to investigate the influence of path complexity on delivery accuracy. The G/R positions detected from the fluoroscopy images (DetPositions) were benchmarked against the G/R angulations retrieved from the control points (CP) of the DWA RT plan and the DWA log files recorded by the treatment console during DWA delivery (LogActed). The G/R rotational accuracy was quantified as the mean absolute deviation ± standard deviation. The maximum G/R absolute deviation was calculated as the maximum 3-dimensional distance between the CP and the closest DetPositions., Results: In the CP versus DetPositions comparison, an overall mean G/R deviation of 0.13°/0.16° ± 0.16°/0.16° was obtained, with a maximum G/R deviation of 0.6°/0.2°. For the LogActed versus DetPositions evaluation, the overall mean deviation was 0.08°/0.15° ± 0.10°/0.10° with a maximum G/R of 0.3°/0.4°. The largest decoupled deviations registered for gantry and ring were 0.6° and 0.4° respectively. No directional dependence was observed between clockwise and counterclockwise rotations. Doubling the dose resulted in a double number of detected points around each CP, and an angular deviation reduction in all cases., Conclusions: An independent geometric quality assurance approach was developed for DWA delivery verification and was successfully applied on diverse trajectories. Results showed that the Vero system is capable of following complex G/R trajectories with maximum deviations during DWA below 0.6°., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Today it is unclear which technique for delivery of an additional boost after whole breast radiotherapy for breast conserved patients should be state of the art. We present a dosimetric comparison of different non-invasive treatment techniques for additional boost delivery., Methods: For 10 different tumor bed localizations, 7 different non-invasive treatment plans were made. Dosimetric comparison of PTV-coverage and dose to organs at risk was performed., Results: The Vero system achieved an excellent PTV-coverage and at the same time could minimize the dose to the organs at risk with an average near-maximum-dose (D2) to the heart of 0.9 Gy and the average volume of ipsilateral lung receiving 5 Gy (V5) of 1.5%. The TomoTherapy modalities delivered an average D2 to the heart of 0.9 Gy for the rotational and of 2.3 Gy for the static modality and an average V5 to the ipsilateral lung of 7.3% and 2.9% respectively. A rotational technique offers an adequate conformity at the cost of more low dose spread and a larger build-up area. In most cases a 2-field technique showed acceptable PTV-coverage, but a bad conformity. Electrons often delivered a worse PTV-coverage than photons, with the planning requirements achieved only in 2 patients and with an average D2 to the heart of 2.8 Gy and an average V5 to the ipsilateral lung of 5.8%., Conclusions: We present advices which can be used as guidelines for the selection of the best individualized treatment.

Background: Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB) compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast., Methods: For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed., Results: PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001). There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04). The dose to the organs at risk (OAR) was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient., Conclusions: SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine.

Background: The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients., Methods: The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described., Results: There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1., Conclusions: Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.

Purpose: This study evaluated the ability of helical tomotherapy to spare the function of the parotid glands in patients with head-and-neck cancer by analyzing dose-volume histograms, salivary gland scintigraphy, and quality of life assessment., Methods and Materials: Data from 76 consecutive patients treated with helical tomotherapy (Hi-Art Tomotherapy) at the University Hospital Brussel were analyzed. During planning, priority was given to planning target volume (PTV) coverage: ≥ 95% of the dose must be delivered to ≥ 95% of the PTV. Elective nodal regions received 54 Gy (1.8 Gy/fraction). A dose of 70.5 Gy (2.35 Gy/fraction) was prescribed to the primary tumor and pathologic lymph nodes (simultaneous integrated boost scheme). Objective scoring of salivary excretion was performed by salivary gland scintigraphy. Subjective scoring of salivary gland function was evaluated by the European Organization for Research and Treatment of Cancer quality of life questionnaires Quality of Life Questionnaire-C30 (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35 (H&N35)., Results: Analysis of dose-volume histograms (DVHs) showed excellent coverage of the PTV. The volume of PTV receiving 95% of the prescribed dose (V95%) was 99.4 (range, 96.3-99.9). DVH analysis of parotid gland showed a median value of the mean parotid dose of 32.1 Gy (range, 17.5-70.3 Gy). The median parotid volume receiving a dose <26 Gy was 51.2%. Quality of life evaluation demonstrated an initial deterioration of almost all scales and items in QLQ-C30 and QLQ-H&N35. Most items improved in time, and some reached baseline values 18 months after treatment., Conclusion: DVH analysis, scintigraphic evaluation of parotid function, and quality of life assessment of our patient group showed that helical tomotherapy makes it possible to preserve parotid gland function without compromising disease control. We recommend mean parotid doses of <34 Gy and doses <26 Gy to a maximum 47% of the parotid volume as planning goals. Intensity-modulated radiotherapy should be considered as standard treatment in patients with head-and-neck cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: HybridArc is a novel treatment technique blending aperture-enhanced optimized arcs with discrete IMRT-elements, allowing selection of arcs with a set of static IMRT-beams. This study compared this new technique to helical Tomotherapy, and RapidArc, in preoperative radiotherapy of rectal cancer., Material and Methods: Twelve rectal cancer patients treated consecutively with Tomotherapy Hi-Art II system were simulated with HybridArc and RapidArc. Treatment plans were designed to deliver homogeneous dose of 46.0Gy to mesorectum and draining lymph nodes, with a simultaneous-integrated-boost to the primary tumor up to a total dose of 55.2Gy. Planning objectives were 95% of prescribed dose to 95% of PTVs, while minimizing the volume of small bowel receiving more than 15Gy (V15) and the mean bladder dose. Dose gradient towards simultaneous-integrated-boost (GI), calculated by dividing the volume receiving more then 52.4Gy (95% of PTV55.2Gy)to the volume of PTV55.2Gy, was kept below 1.5. Mean beam-on time and amount of MUs were also analyzed., Results: PTV swere adequately covered by all plans. Significant advantage was found for Tomotherapy in sparing small bowel (V15 = 112.7cm(3)SD73.4cm(3)) compared to RapidArc (133.4cm(3)SD75.3cm(3)) and HybridArc (143.7cm(3)SD74.4cm(3)) (p < 0.01). The mean bladder dose was better with RapidArc (20.6GySD2.2Gy) compared to HybridArc (24.2Gy SD4.3Gy) and Tomotherapy (23.0GySD4.7Gy) (p < 0.01). The mean beam-on time was significantly lower (p < 0.01) for HybridArc (2.7min SD0.8) and RapidArc (2.5min SD0.5) compared to Tomotherapy (11.0min SD0.7). The total amount of MUs was significantly (p < 0.01) lower for RapidArc (547SD44)compared to HybridArc (949 SD153)., Conclusions: HybridArc is a feasible solution for preoperative RT with a simultaneous-integrated-boost in rectal cancer patients. It achieved similar PTV coverage with significant lower beam-on time, but less efficient in sparing small bowel and bladder compared to Tomotherapy and RapidArc. The added value of HybridArc is that the treatment modality can be implemented on every LINAC equipped with Dynamic-Conform-Arc and IMRT treatment techniques, while maintaining the same QA-schemes.

Purpose: The addition of concomitant chemotherapy to preoperative radiotherapy is considered the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control (LC), but has no impact on survival or the incidence of distant metastases. In addition, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively, preoperative helical tomotherapy with a simultaneous integrated boost (SIB)., Methods and Materials: A total of 108 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. Patients with an anticipated circumferential resection margin (CRM) of less than 2 mm, based on magnetic resonance imaging, received a SIB to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0., Results: A total of 102 patients presented with cT3-4 tumors; 57 patients entered the boost group and 51 the no-boost group. One patient in the no-boost group developed a radio-hypersensitivity reaction, resulting in a complete tumor remission, a Grade 3 acute and Grade 5 late enteritis. No other Grade ≥3 acute toxicities occurred. With a median follow-up of 32 months, Grade ≥3 late gastrointestinal and urinary toxicity were observed in 6% and 4% of the patients, respectively. The actuarial 2-year LC, progression-free survival and overall survival were 98%, 79%, and 93%., Conclusions: Preoperative helical tomotherapy displays a favorable acute toxicity profile in patients with cT3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and resulted in a promising LC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Complete metastasectomy provides a real chance for long-term survival in patients with oligometastatic colorectal cancer (CRC). For inoperable patients, we evaluated in this study intensity-modulated and image-guided radiotherapy (IMRT-IGRT) by helical tomotherapy., Methods: Twenty-four CRC patients with ≤ 5 metastases were enrolled, receiving a dose of 50 Gy in fractions of 5 Gy. No limitations concerning dimension or localization of the metastases were imposed. Whole body PET-CT was performed at baseline and 3 months after the initiation of RT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0., Results: A total of 53 metastases were treated. Seventeen patients (71%) received previously ≥ 1 line of chemotherapy for metastatic disease, displaying residual (n = 7) or progressive (n = 10) metabolic active oligometastatic disease at time of inclusion. Most common sites were the lung, liver and lymphnodes. One patient (4%) experienced grade 3 dysphagia. Twenty-two patients were evaluated by post-treatment PET-CT. Twelve patients achieved a complete (n = 6) or partial (n = 6) metabolic response, resulting in an overall metabolic response rate of 55%. At a median follow-up of 10 months, 7 patients (29%) are in remission, of which 5 received previous chemotherapy with residual oligometastatic disease at time of inclusion. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 14% and 78%., Conclusions: Helical tomotherapy delivering 10 fractions of 5 Gy resulted in a metabolic response rate of 55%, and appeared to be attractive as consolidation of inoperable oligometastatic disease after effective chemotherapy., Trial Registration: Eudract 2008-008300-40; NCT00807313.

Purpose: To assess the predictive or comparative value of volumetric changes, measured on daily megavoltage computed tomography during radiotherapy for lung cancer., Patients and Methods: We included 80 patients with locally advanced non-small-cell lung cancer treated with image-guided intensity-modulated radiotherapy. The radiotherapy was combined with concurrent chemotherapy, combined with induction chemotherapy, or given as primary treatment. Patients entered two parallel studies with moderately hypofractionated radiotherapy. Tumor volume contouring was done on the daily acquired images. A regression coefficient was derived from the volumetric changes on megavoltage computed tomography, and its predictive value was validated. Logarithmic or polynomial fits were applied to the intratreatment changes to compare the different treatment schedules radiobiologically., Results: Regardless of the treatment type, a high regression coefficient during radiotherapy predicted for a significantly prolonged cause-specific local progression free-survival (p = 0.05). Significant differences were found in the response during radiotherapy. The significant difference in volumetric treatment response between radiotherapy with concurrent chemotherapy and radiotherapy plus induction chemotherapy translated to a superior long-term local progression-free survival for concurrent chemotherapy (p = 0.03). An enhancement ratio of 1.3 was measured for the used platinum/taxane doublet in comparison with radiotherapy alone., Conclusion: Contouring on daily megavoltage computed tomography images during radiotherapy enabled us to predict the efficacy of a given treatment. The significant differences in volumetric response between treatment strategies makes it a possible tool for future schedule comparison., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To assess the internal organ motion of the cervix and uterus by megavoltage computed tomography (MVCT) during intensity-modulated radiotherapy (IMRT)., Methods and Materials: Ten patients with Stage IIB-IVA cervical cancer underwent daily MVCT imaging. Internal organ motion was evaluated on 150 pretreatment MVCT images by measuring shifts in their boundaries between the MVCT and kilovoltage (kV) planning CT scan in the anterior, posterior, left and right lateral, and superior and inferior direction. Additional intrafractional patient movement was evaluated on 50 posttreatment MVCT images., Results: Measured cervical motion (mean +/- SD) was 0.4 +/- 10.1 mm in the anterior, -3.0 +/- 6.9 mm in the posterior direction, -3.5 +/- 4.9 mm in the left and 0.2 +/- 4.5 mm in the right lateral direction, 2.2 +/- 8.0 mm in the superior and 0.5 +/- 5.0 mm in the inferior direction. Compared to the cervix, larger uterine motion was observed. Patient movement during treatment was limited to 1.1 +/- 1.3 mm, -0.3 +/- 1.6 mm, and 0.2 +/- 2.3 mm in anteroposterior, laterolateral and superoinferior direction respectively., Conclusions: MVCT imaging can be used to study patient setup accuracy and cervical and uterine motion during IMRT. This data may be used to refine treatment margins., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To prospectively assess the feasibility, toxicity, and local control of a class solution protocol of moderately hypofractionated tomotherapy in Stage III, inoperable, locally advanced non-small-cell lung cancer patients., Methods and Materials: Eligible patients were treated according to a uniform class solution (70.5 Gy in 30 fractions) with fixed constraints and priorities using helical tomotherapy. Toxicity monitoring was performed using the Radiation Therapy Oncology Group criteria and the National Cancer Institute Common Terminology Criteria and Adverse Events (CTCAE) version 3.0. Pulmonary function tests were performed at the start and repeated at 3 months after treatment., Results: Our class solution resulted in a deliverable plan in all 40 consecutive patients. Acute Grade 3 lung toxicity was seen in 10% of patients. Two patients died during acute follow-up with pulmonary toxicity. Correlations were found between changes in pulmonary function test results and mean lung dose or the lung volume receiving 20 Gy (V(20)). The correlation was strongest for lung diffusion capacity for carbon monoxide. A V(20) of >27% and >32% were predictive for Grades 2 and 3 acute lung toxicity respectively (p < 0.05). Late Grade 3 toxicity was exclusively pulmonary, with an incidence of 16%. Overall Grade 3 lung toxicity correlated with a mean lung dose of >18 Gy and a median lung dose of >5 Gy (p < 0.05). Median survival was 17 months, and the 1-year and 2-year local progression-free survivals were 66% and 50%, respectively., Conclusion: The current class solution using moderately hypofractionated helical tomotherapy in patients with locally advanced non-small-cell lung cancer is feasible. Toxicity was acceptable and in line with other reports on intensity-modulated radiotherapy. The local progression-free survival was encouraging considering the unselected population., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: Preoperative (chemo)radiotherapy is considered to be standard of care in locally advanced rectal cancer, but is associated with significant small-bowel toxicity. The aim of this study was to explore to what extent helical tomotherapy and daily megavolt (MV) CT imaging may reduce the irradiated volume of small bowel., Methods and Materials: A 3D-conformal radiotherapy (3D-CRT) plan with CTV-PTV margins adjusted for laser-skin marks (15, 15, and 10 mm for X, Y, and Z directions, respectively) was compared with helical tomotherapy (IMRT) using the same CTV-PTV margins, and to helical tomotherapy with margins adapted to daily MV-CT imaging (IMRT/IGRT; 8, 11, 7, and 10 mm for X, Y(ant), Y(post) and Z resp.) for 11 consecutive patients. The planning goals were to prescribe 43.7 Gy to 95% of the PTV, while minimizing the volume of small bowel receiving more than 15 Gy (V(15 SB))., Results: The mean PTV was reduced from 1857.4 +/- 256.6 cc to 1462.0 +/- 222.3 cc, when the CTV-PTV margins were adapted from laser-skin marks to daily MV-CT imaging (p < 0.01). The V(15 SB) decreased from 160.7 +/- 102.9 cc to 110.9 +/- 74.0 cc with IMRT and to 81.4 +/- 53.9 cc with IMRT/IGRT (p < 0.01). The normal tissue complication probability (NTCP) for developing Grade 2+ diarrhea was reduced from 39.5% to 26.5% with IMRT and to 18.0% with IMRT/IGRT (p < 0.01)., Conclusion: The combination of helical tomotherapy and daily MV-CT imaging significantly decreases the irradiated volume of small bowel and its NTCP.

Purpose: To explore the efficacy and toxicity profile of helical tomotherapy in the preoperative treatment of patients with rectal cancer., Patients and Methods: Twenty-four patients with T3/T4 rectal cancer were included in this nonrandomized noncontrolled study. A dose of 46 Gy in daily fractions of 2 Gy was delivered to the presacral space and perineum if an abdominoperineal resection was deemed necessary. This dose was increased by a simultaneous integrated boost to 55.2 Gy when the circumferential resection margin was less than 2 mm on magnetic resonance imaging. Acute toxicity was evaluated weekly. Metabolic response was determined in the fifth week after the end of radiotherapy by means of fluorodeoxyglucose-positron emission tomography scan. A metabolic response was defined as a decrease in maximal standardized uptake value of more than 36%., Results: The mean volume of small bowel receiving more than 15 Gy and mean bladder dose were 227 ml and 20.8 Gy in the no-boost group and 141 ml and 21.5 Gy in the boost group. Only 1 patient developed Grade 3 enteritis. No other Grade 3 or 4 toxicities were observed. Two patients developed an anastomotic leak within 30 days after surgery. The metabolic response rate was 45% in the no-boost group compared with 77% in the boost group. All except 1 patient underwent an R0 resection., Conclusions: Helical tomotherapy may decrease gastrointestinal toxicity in the preoperative radiotherapy of patients with rectal cancer. A simultaneous integrated radiation boost seems to result in a high metabolic response rate without excessive toxicity.