The bacterial and archaeal communities and their dynamics from start-up to stable biogas formation were investigated using a novel anaerobic digester system designed for efficient digestion of lignocellulosic biomass. The lab-scale reactor systems each consisted of an up-flow anaerobic solid-state reactor (UASS) connected to an anaerobic filter (AF) with recirculation of the liquid phase. Mesophilic and thermophilic digestion was carried out in parallel systems. Both reactor systems were fed with wheat straw as sole substrate at an organic loading rate of 2.5 gVS L -1 d over a time period of 218 days. Samples were taken from the effluent of UASS and AF and of digestates. Additionally, at the last sampling day, biofilm carriers from the AF were analyzed. Terminal restriction fragment length polymorphism (T-RFLP) of PCR-amplified 16S rRNA genes was applied to analyze changes in the biocoenosis structure over time. Furthermore, for the samples of the last sampling, 16S rRNA gene libraries were constructed to obtain detailed insights into the taxonomical composition of the microbial communities responsible for biogas formation at stable process conditions. The results offer a considerable higher taxonomic variety of Bacteria compared to Archaea, whereas the mesophilic communities were much more diverse than the thermophilic. Furthermore the mesophilic and thermophilic communities were entirely different – only five common OTUs were found at both temperature regimes. The fingerprinting pattern showed a clear alteration during and even after establishment of a steady-state biogas formation process.
Purpose: Monte Carlo dose calculations are considered to be the gold standard by which other techniques are compared, particularly for complex geometries with regions of electronic disequilibrium. The major disadvantage of Monte Carlo is the associated long calculation times. This necessitates limiting the number of histories and/or using interpolative techniques, potentially reducing accuracy. ProACTive is an irreducible vector space method of dose calculation with computation times significantly faster than Monte Carlo. The purpose of the work is to validate ProACTiveˈs accuracy.Method: ProACTive calculations were compared to measurement and/or EGS4/PRESTA Monte Carlo for both homogenous and heterogeneous geometries for 6MV and 18MV. Sufficient Monte Carlo histories were run to minimize statistical uncertainty. Depth dose and profile measurements were taken from an average of measurements obtained on 40 Varian linear accelerators commissioned in the last several years. Heterogeneous phantoms included a complex phantom consisting of water, aluminum and lung irradiated by a 2×2 cm2 18 MV x-ray beam as described by Mohan and Rogers (ICCR2000 Proceedings). Results: ProACTive calculation times were significantly faster than Monte Carlo run with a large number of histories. For homogenous geometries, ProACTive calculations showed good agreement with measurement for a wide range of depths and beam sizes, both on and off axis. For the ICCR2000 phantom, ProACTive and Monte Carlo showed overall good agreement. Both calculation methods showed some difference compared to measurement, especially at a density boundary. It is not clear whether the differences are real or due to uncertainty in the measurements and their interpretation for this extreme geometry. Conclusions: For the geometries tested, ProACTive shows good agreement with measurement and similar computational accuracy to Monte Carlo when the latter is run with sufficient histories to minimize statistical uncertainty. ProACTiveˈs accuracy and computational time make it a feasible clinical solution to accurate dose calculation.
Purpose: Commissioning a linear accelerator is a large task, often requiring 6 weeks or more of intensive effort. We wished to establish whether it is possible to accurately commission a linac with a greatly reduced data set, supplemented by averaged beam data taken from similar machines. Methods: We collected 6MV photon data (beam profiles and output factors) from 40 Varian linacs, and looked at the amount of variation between machines in our measured data set, and between our data and vendor-supplied ‘gold’ data. From this, we determined a limited data set that would be sufficient to characterize the photon beam fully when supplemented with averaged data from other machines. We then tested the limited data set approach by comparing a photon model in the Eclipse planning system generated with either a fully measured data set, or the limited data set supplemented with averaged data. Results: The largest amount of variability in the photon output factor data came from the smallest and largest fields in the data set. The largest variability in beam profiles was in small fields, and in wedged field profiles. In our limited data set, we reduced the number of individual fields measured by 60%, and the number of measured output factors by 80%. We estimate that these reductions could reduce commissioning time by more than 40 hours. Point comparisons of planning system dose models created from full and limited data sets gave an average difference of 0.1 +− 0.17% for open fields, and 0.2 +− 0.44% for wedged fields, with the maximum difference seen for all fields of 1.5%. Conclusion: We have demonstrated that it is possible, using an averaged data set from many accelerators, to accurately commission an accelerator beam with a greatly reduced data set.
Quantitative real-time PCR (Q-PCR) is commonly applied for the detection of certain microorganisms in environmental samples. However, some environments, like biomass-degrading biogas fermenters, are enriched with PCR-interfering substances. To study the impact of the DNA extraction protocol on the results of Q-PCR-based analysis of the methane-producing archaeal community in biogas fermenters, nine different protocols with varying cell disruption and DNA purification approaches were tested.Differences in the quantities of the isolated DNA and the purity parameters were found, with the best cell lysis efficiencies being obtained by a combined lysozyme/SDS-based lysis. When DNA was purified by sephacryl columns, the amount of DNA decreased by one log cycle but PCR inhibitors were eliminated sufficiently.In the case of detection of methanogenic Archaea, the chosen DNA isolation protocol strongly influenced the Q-PCR-based determination of 165 rDNA copy numbers. For example, with protocols including mechanical cell disruption, the 16S rDNA of Methanobacteriales were predominantly amplified (81-90% of the total 16S rDNA copy numbers), followed by the 165 rDNA of Methanomicrobiales (9-18%). In contrast, when a lysozyme/SDS-based cell lysis was applied, the 16S rDNA copy numbers determined for these two orders were the opposite (Methanomicrobiales 82-95%, Methanobacteriales 4-18%). In extreme cases, the DNA isolation method led to discrimination of some groups of methanogens (e.g. members of the Methanosaetaceae).In conclusion, for extraction of high amounts of microbial DNA with high purity from samples of biogas plants, a combined lysozyme/SDS-based cell lysis followed by a purification step with sephacryl columns is recommended. (C) 2010 Elsevier GmbH. All rights reserved.
Purpose: ProACTive™, a new dose calculation method has been developed that provides accuracy comparable or exceeding Monte Carlo calculations with computational speed gains that may exceed two orders of magnitude. Method and Materials: A transport simulation method has been developed fully utilizing computer memory and hierarchical pre-computation to produce high resolution, high quality dose computations for use in medical treatment planning. The advent of computers with Gigabytes of random access memory allows direct transport response coupling for distant finite surfaces and volumes. Coupling over large distances, with many angular finite groups minimizes ray-effects, providing consistent high accuracy dose computations through heterogeneous systems. This allows direct modeling of the forward peaked highly anisotropic scattering and transport of photons and electrons. The discrete nature of these computations allow for reverse engineering of LINAC filters, and this is accomplished using minimal wide beam depth dose and one depth (typically 10 cm) profile data. The method of invariant imbedding is employed to produce shape functions to speed computation of relatively low important scattered radiation. ProACTive™ calculations have been compared to both measurement and published Monte Carlo calculations for number of homogenous and heterogeneous geometries, including interface regions. Results: In homogenous, water equivalent geometries, agreement among ProACTive™, published Monte Carlo and measurement was excellent, typically within 1–2%. In heterogeneous geometries, similar results were obtained. On one processor ProACTive™ can run in minutes and is inherently parallelizable. Conclusion: To obtain reasonable calculation speeds, variance reduction techniques are often employed in Monte Carlo calculations resulting in degradation of accuracy due to statistical artifacts. ProACTive™ uses finite angular and energy groups accounting for in-group spectral shifts during collision epochs, providing consistent high accuracy without inherent statistical fluctuations associated with Monte Carlo. Conflict of Interest: Research Sponsored By Applied Computational Technologies, LLC
To analyze the initial clinical outcomes for breast cancer patients treated with intensity-modulated radiation therapy (IMRT) in a large integrated cancer center network. A total of 495 patients with breast cancer received IMRT following breast conserving surgery among nine cancer centers. Seven community cancer centers span a 100-mile radial distance from the two central academic sites. All nine cancer centers followed the same clinical pathway guidelines for the radiotherapeutic management of breast cancer. IMRT planning for all centers was performed at one central location, D3 Advanced Radiation Planning Service. The median IMRT prescription dose was 50 Gy followed by a boost with median dose of 10 Gy. The median breast volume was 918 cm3. The median Dose Homogeneity Index (DHI) was 93%. The median % of ipsilateral lung volume receiving >20 Gy was 4.6%. For left breast IMRT, the median % heart volume receiving more than 5% of prescription dose was 13.1. There was no statistical difference in the mean DHI, heart and lung dose between the academic and community sites. For all patients, NCI CTC Grades 0,1,2,3 for acute skin erythema was 16%, 55%, 28%, and 1%, respectively. The rates of Grade 0,1,2,3 acute skin desquamation were 75%, 20%, 4%, and 1%, respectively. There was no statistically significant difference in acute skin toxicities (>grade 2) among the academic and community cancer centers. With centralized processes, IMRT can be safely and effectively delivered in a large health system with an admixture of academic and community centers but long-term follow-up is necessary.
Purpose: To evaluate the interfractional reproducibility of respiration-induced lung tumors motion, defined by their centroids and the intrafractional target motion range.Methods and Materials: Twentythree pairs of four-dimensional/computed tomography scans were acquired for 22 patients. Gross tumor volumes were contoured, Clinical target volumes (CTVs) were generated. Geometric data for CTVs and lung volumes were extracted. The motion tracks of CTV centroids, and CTV edges along the cranio-caudal, anterior-posterior, and lateral directions were evaluated. The Pearson correlation coefficient for motion tracks along the cranio-caudal direction was determined for the entire respiratory cycle and for five phases about the end of expiration.Results: The largest motion extent was along the cranio-caudal direction. The intrafractional motion extent for five CTVs was < 0.5 cm, the largest motion range was 3.59 cm. Three CTVs with respiration-induced displacement > 0.5 cm did not exhibit the similarity of motion, and for 16 CTVs with motion > 0.5 cm the correlation coefficient was > 0.8. The lung volumes in corresponding phases for cases that demonstrated CTVs motion similarity were reproducible. No correlation between tumor size and mobility was found.Conclusion: Target motion reproducibility seems to be present in 87% of cases in our dataset. Three cases with dissimilar motion indicate that it is advisable to verify target motion during treatment. The adaptive adjustment to compensate the possible interfractional shifts in a target position should be incorporated as a routine policy for lung cancer radiotherapy. (c) 2008 Elsevier Inc.
Cone-beam CT (CBCT) allows direct imaging of the tumor volume to reposition patients with head and neck (H&N) tumors prior to treatment at the expense of increased patient dose and accelerator time. kV imaging of bony landmarks is faster at significantly lower patient dose. This study compared the two techniques to determine if kV imaging could be a suitable substitute for CBCT in patients with H&N cancers. Ten patients with H&N cancers were immobilized using a thermoplastic mask and treated using IMRT on a Varian Trilogy™ linear accelerator using daily image guidance. Each day, prior to treatment and with the patient in the treatment position, orthogonal kV radiographs were obtained and compared to reference DRRs. Bony landmark-based 2D-2D matching was performed to determine translational table (patient) shifts along the A-P, L-R, and S-I axes. After physician review and approval, the shifts were performed and the patient was treated. Once or twice per week a CBCT was obtained prior to treatment. Depending on time constraints, the CBCT was either performed in addition to the orthogonal radiographs or in place of them. Each CBCT was compared to a reference CT obtained at the time of simulation and 3D-3D matching was performed. In contradistinction to the 2D-2D matching, the 3D-3D matching used soft tissue in and around the tumor volume. On the days that CBCT was performed, the table (patient) was shifted using the 3D-3D match after physician review and approval. Comparison of the table shifts determined using either 2D-2D or 3D-3D matching was made and the statistical significance evaluated. PTV margins were calculated using the formula PTV = 2.5Σ + 0.7σ where Σ and σ are the systematic and random errors as defined by the Netherlands Cancer Institute. An average of 26.4 ± 7.8 2D-2D and 5.7 ± 1.2 3D-3D matches were made per patient. Average corrections are (L-R, A-P, S-I) (-0.11 ± .43, 0.00 ± .21, 0.01 ± .31) and (-0.03 ± .41, 0.12 ± .29, 0.04 ± .29) cm, respectively. The required PTV margins (in the absence of corrective table shifts) are (0.66, 0.33, 0.51) and (0.84, 0.55, 0.52) cm using 2D-2D or 3D-3D matching respectively. For a given direction, the 2D-2D systematic and random errors were approximately equal. Errors in the S-I direction were similar for 2D-2D and 3D-3D. In the A-P and L-R directions, the random errors computed from 3D-3D matching were similar to those obtained from the 2D-2D matching, but the 3D-3D matching derived systematic errors were 0.2 cm greater. The slightly larger systematic errors seen with 3D-3D matching using CBCT imaging of the tumor may be due to tumor changes over time not seen using bony landmarks or difficulty in delineating the tumor volume. Detailed review of each patient, especially on days in which both 2D-2D and 3D-3D matching was performed indicates that kV imaging using bony landmarks may be an acceptable substitute for CBCT imaging of patients with H&N cancers where immobilization is quite good. An imaging schedule in which CBCT is performed once or twice per week to check for gradual changes in the tumor volume, shape or position with 2D-2D matching of KV images on the other days may be sufficient. This may not be necessarily the case for other sites.
To analyze and report the initial clinical outcomes for head and neck cancer (HNC) patients (pts) treated with IMRT in a large integrated cancer center network. Between January 2002-June 2006, 604 patients with median age of 62 (range 21–101) with HNC among 13 cancer centers received definitive or adjuvant radiation therapy using IMRT for HNC. The 12 community cancer centers spanned a 70-mile radial distance from the flagship academic cancer center. 248 (41% of total) patients were treated at the academic center and 356 (59%) patients received IMRT at one of the 12 community cancer centers. 66% of HNC were of squamous cell carcinoma histology and 60% of all HNC pts received concurrent chemotherapy. 64% received definitive treatment with IMRT while 22% received adjuvant treatment with IMRT. All 13 cancer centers followed the same clinical pathway guidelines for the radiotherapeutic management of HNC which included specific details on planning target volumes (PTV) design and dose prescription for IMRT. The radiation oncologist at each site contoured the PTV on images from the planning CT scan and defined the dose prescription for each patient. Based on these contoured images, IMRT planning for all centers was performed at one central location, D3 Radiation Planning. The median dose was 66.6 Gy. During radiation treatment, all patients were evaluated on a weekly basis for any toxicities which were also assessed during follow-up visits. Outcomes were compared between the academic flagship center (n = 1) and the community cancer centers (n = 12) within the integrated cancer network. The median follow up was 9 months (range 0–4.2 years). There were 148 deaths in total thus far. There were 30 local recurrences, 35 loco-regional recurrences, and 30 distant recurrences. The median time to recurrence was 6.3 months. 15% of all patients had Grade 3–4 acute mucositis. 75% of all patients did not require any treatment breaks. 57% of patients had only Grade 1 late xerostomia. The median parotid volume receiving more than 26 Gy (V26 Gy) is 46%. When comparing outcomes between the academic center and the community centers in the integrated network, there was no statistically significant difference between survival (p = 0.14) or local, loco-regional, and distant recurrence (p = 0.47), or median time to recurrence (p = 0.24). There was also no difference in acute or late xerostomia (p = 0.46 and p = 0.17, respectively) between the academic and community centers within the network. The dosimetric data including the parotid V26 Gy were not statistically different (p = 0.44). Despite the extreme complexity of HNC IMRT, this modality can be safely and effectively delivered in a large integrated health-care network with an admixture of academic and community centers. Centralized IMRTplanning and quality assurance processes including the clinical pathways implementation can effectively standardizes treatment and can further ensure a relatively uniform quality of care despite great geographic distances between centers.
Purpose: In radiotherapy treatments of breast patients, respirations may introduce uncertainties in target and heart locations. This study is to investigate the dosimetric impacts of these uncertainties in breast radiation treatments. Method and Materials: A 4D CT scan and a conventional helical CT scan set were acquired on each of 7 left breast patients and 5 right breast patients. Using the helical CT scan, a conventional 3D conformal plan, consisting of two tangential beams, was generated per physician's evaluation and decision. The 4D CT scan set was divided into 10 phases over the respiratory cycle. On each phase, treatment target and heart were contoured. Dose distributions were generated using the same beams as in the conventional plan. Software was developed to compute the cumulative dose distribution (4D doses) from all the phases. This 4D CT image based cumulative dose distribution would be closer to that in reality with motions taken into account. Various dosimetric parameters were obtained for treatment target and heart from the conventional plan and from the 4D cumulative dose distributions and compared to deduce the motion induced dosimetric impacts in breast radiation treatments. Studies were performed for both whole and partial breast treatments. Results: For whole breast treatment, the motion induced changes in D95, Dmax, and Dmin of PTV were 0.88% ± 20%, −0.28 ± 0.65%, and −10.17% ± 47%, respectively. For left breast, the motion induced Dmax change in heart was 22% ± 48%. For partial breast treatments, the motion induced changes in V90 and Dmin of CTV were 1.6% ± 2.7% and 3% ± 4%, respectively. Conclusions: Breathing motion may cause cold spots in the whole breast treatment, and may compromise treatment quality for some patients. It may also increase heart maximum dose. However, for the partial breast treatment, the motion impact may be insignificant with properly selected margin size.Supported in part by Varian Medical Systems.
Purpose: Varian's RPM™ system for respiration induced tumor motion management allows acquisition of CT images and gated treatments under free breathing. 4DCT may not be possible because of lack availability of appropriate CT hardware or software. This study evaluated whether a breath hold CT scanning technique can be used as a substitute for a 4DCT scan. Materials and Methods: A 4DCT scan is obtained on a 4 slice GE Lightspeed™ scanner with the patient breathing freely and the respiratory period regulated using audiovisual cues from RPM™. Additional helical scans are obtained using an end inhalation or exhalation breath hold modified gating method (MGM). The PTV is drawn on the MGM scan(s) and for each of phase of the 4DCT scan. Comparison of target volume, centroid and extent of target volume is made between the MGM scan and the corresponding phase of the 4DCT scan. A treatment plan is developed using the MGM scan. Dose is recalculated using the 4DCT scan with the beam's isocenter and apertures obtained from the MGM scan. DVH comparison is made. Results: 20 patients had both a 4DCT scan and at least one MGM scan. 8 patients exhibited respiration induced target motion of >5 mm during free breathing. Maximum target motion observed was 25 mm. For 14 end inhalation scans, 9 passed, 3 passed marginally, and 2 failed the equivalency tests to the corresponding 4DCT scan. For 18 end exhalation scans, 14 passed, 4 passed marginally, and 0 failed the equivalency tests to the corresponding 4DCT scan. Conclusion: All end exhalation breath hold scans are suitable substitutes for the corresponding phase 50 4DCT scan. However only 6/18 patients exhibited sufficient (>5 mm) respiration induced target motion on which to base any conclusions about the suitability of MGM. Conflict of Interest: Research supported by Varian Medical Systems.
Purpose: To investigate the reproducibility of lung tumors motions and their characteristics during the course of the treatment. Materials and Methods: Two 4DCT scans were obtained at an interval of about three weeks with a GE‐scanner and Varian's RPM System under free breathing for 13 patients. Each respiration cycle had 10 phases. 14 GTVs and 10 lungs in all phases were contoured. Geometrical characteristics of these structures were obtained with Eclipse TPS for the motion reproducibility analysis. Results: The GTVs of the initial scans ranged from 2.0cc to 280.5cc with a median of 50.3cc. Their median relative change in the second scan was a 28% decrease. The 3D extent of the respiration‐induced motion of the GTVs' centroids in the first scan ranged from 0.34cm to 1.78cm with a median of 0.90cm. For the second scan it was 0.13cm, 1.99cm, and 0.89cm, respectively. The largest motion was in a projection on a sagittal plane. The overall displacements of the GTVs' edges exhibited same trend. These motion tracks from two scans overlapped along DICOM directions. The median change of phase 50 lung volumes in both scans relative to the tidal volume at the first scan was −12% for ipsilateral and −11% for contralateral lungs. The median tidal volume change between scans relative to the first scan volume was 8% for ipsilateral and 4% for contralateral lungs. Conclusion: Most of the patients results show reproducible patterns of motion. The hysteresis of the motion varies between scans. This might be due to GTV changes during the treatment. A large and anisotropic shape change perturbs the initial motion trajectory, however general patterns appear repetitive. The respiratory changes of lung volumes were similar. They are not indicative of the GTVs motion reproducibility.
Purpose: In IMRT treatments, the ultimate QA procedure is to carry out in‐vivo dosimetry measurement to ensure the accuracies of both patient setup and beam delivery. This study was designed to explore the use of in‐vivo diode dosimetry measurement for QA of IMRT treatments. Method and Materials: IMRT plans were generated based on a set of CT scans of a head & neck anthropomorphic phantom. Corresponding IMRT QA verification plans were also generated. Diode calibration readings (Rc) were obtained for each beam during the routine dose verification QA process. During verification, a diode was placed along the beam central axis on the surface of a flat QA phantom at the SSD specified in the QA plan. Radiation was delivered dynamically using the same dynamic MLC files that were to be used for the patient treatment. For in‐vivo measurements, the anthropomorphic phantom was setup according to the treatment plan. For each beam, a diode was placed along the central axis at the beam surface entry point. Radiation was then delivered according to the plan and the diode reading (Ri) was recorded. If both the setup and the beam delivery were correct, Ri should be in agreement with quantity Rc*fSSD within certain uncertainty (fSSD is SSD correction factor); otherwise, it would be an indication of incorrect patient setup or incorrect beam delivery. Results: It was found that the calibration diode readings followed the SSD inverse square law within an uncertainty of 0.4%. urn:x-wiley:0094-2405:media:mp7840:mp7840-math-0001 The derived in‐vivo diode readings (Rc*fSSD) were in agreement with those measured ones within 3.6% for three beams at different gantry angles, with an average difference of 1.8%. Conclusion: With a proper calibration method, diode verification can be used relatively accurately for in‐vivo measurements to check on the accuracies of patient setup and beam delivery for IMRT treatments.
Purpose: To review IMRT QA measurements from several of the 50+ institutions for which we provide IMRT treatment plans and determine if institutional, anatomic site, or measurement biases exist. Method and Materials: For each patient receiving IMRT, the treatment plan is delivered to a solid water phantom and the dose measured using a small volume ion chamber and with a single EDR film placed 1 cm above the chamber plane. Of the almost 3000 IMRT treatment plans calculated and delivered in 2004, more than 1000 random, de‐identified plans were reviewed. Ratios of chamber/calculated and film‐center/calculated doses were tabulated for six anatomic sites (breast, prostate, pelvis, head & neck, brain, and other). Film dose distributions were compared to calculations using one of several commercially available QA packages. Results: The institutions with the best results had average errors of less than ±0.5% (i.e. randomly distributed about zero) with standard deviations of 1.25–1.50%. A few centers had average errors and standard deviations approaching 3%, indicating a bias in which a systematic dose measurement error was found. Agreement between chamber and film center dose was also institution specific with the best results found for those centers that had the lowest errors compared to calculation. One institution had excellent agreement between chamber and calculation (−0.2±1.7%), but 2–3% lower film dose. Although exceptions were found, little variation in the agreement between chamber measurement and calculation occurred as a function of anatomical site. Conclusion: Since all treatment plans were calculated in one central location and many centers had excellent agreement between measurement and calculation, it is likely that the higher errors were due to measurement technique rather than errors in the dose calculation. Error was not anatomic site dependent possibly due to the purposeful placement of the ion chamber in a region of relatively uniform dose.
Purpose/Objective: To evaluate the incidence of acute skin toxicity in patients with breast cancer treated with intensity modulated radiation therapy (IMRT) following breast conserving surgery.Materials/Methods: Between February 2003 and January 2005, 506 patients with early stage breast cancer underwent breast conservation surgery and definitive breast irradiation using 2-angle tangential field IMRT. The median dose delivered to the entire breast was 50 Gy in 25 fractions. Electron beam boost to the lumpectomy cavity was delivered via enface electrons with a median dose of 10 Gy for a median total dose of 60 Gy in 30 fractions. Throughout the course of radiation treatment, all patients were evaluated on a weekly basis by the treating radiation oncologist for acute skin toxicity including erythema and desquamation which were graded using the RTOG toxicity scale.Results: The median breast volume (TV) in this cohort of patients was 894 cc (range 104–3387 cc). For all patients, the incidence of acute erythema grades 0,1,2, and 3 were 23%, 45%, 31%, and 1%, respectively. The rates of acute skin desquamation grades 0,1,2, and 3 were 81.5%, 14%, 4%, and 0.5%, respectively. The median maximum dose delivered to the TV was 55 Gy using IMRT. The median % of TV receiving more than the prescribed dose was 83%. The median % of TV receiving more than 110% and less than 95% of prescribed dose was 0% and 8%, respectively. The incidence of desquamation significantly correlated with TV (p<0.001), max dose to TV (p=0.017) and % TV receiving more than prescribed dose (p=0.016). There was no significant correlation of these dosimetric quantities or TV to skin erythematic grade.Tabled 1Correlation Analysis of Breast Volume and Dosimetric Values with Acute Skin Desquamation Toxicity for Breast IMRT Purpose/Objective: To evaluate the incidence of acute skin toxicity in patients with breast cancer treated with intensity modulated radiation therapy (IMRT) following breast conserving surgery. Materials/Methods: Between February 2003 and January 2005, 506 patients with early stage breast cancer underwent breast conservation surgery and definitive breast irradiation using 2-angle tangential field IMRT. The median dose delivered to the entire breast was 50 Gy in 25 fractions. Electron beam boost to the lumpectomy cavity was delivered via enface electrons with a median dose of 10 Gy for a median total dose of 60 Gy in 30 fractions. Throughout the course of radiation treatment, all patients were evaluated on a weekly basis by the treating radiation oncologist for acute skin toxicity including erythema and desquamation which were graded using the RTOG toxicity scale. Results: The median breast volume (TV) in this cohort of patients was 894 cc (range 104–3387 cc). For all patients, the incidence of acute erythema grades 0,1,2, and 3 were 23%, 45%, 31%, and 1%, respectively. The rates of acute skin desquamation grades 0,1,2, and 3 were 81.5%, 14%, 4%, and 0.5%, respectively. The median maximum dose delivered to the TV was 55 Gy using IMRT. The median % of TV receiving more than the prescribed dose was 83%. The median % of TV receiving more than 110% and less than 95% of prescribed dose was 0% and 8%, respectively. The incidence of desquamation significantly correlated with TV (p<0.001), max dose to TV (p=0.017) and % TV receiving more than prescribed dose (p=0.016). There was no significant correlation of these dosimetric quantities or TV to skin erythematic grade.
Purpose/Objective: Limited data exists for dose-volume relationship of parotid gland when patients receive chemoradiation. The purpose of this study is to evaluate the relationship between parotid dose and severity of acute and "early" late xerostomia for patients receiving chemoradiation for head and neck cancers. Materials/Methods: 333 patients with head and neck cancer (HNC) were treated with intensity modulated radiation therapy (IMRT). Of these, 209 patients (63%) were treated with concurrent chemotherapy & radiation and 124 (37%) were treated with radiation alone. All patients underwent a simulation procedure simulated for IMRT treatment planning in a Uni-frame® head immobilization system (MED-TEC Corp, Orange City, IA) and centrally planned on Varian Eclipse (version 6.5) in a distributed cancer network. The superficial lobe of the parotid gland was contoured and the dose volume histogram for parotid tissue was evaluated using the Eclipse planning system. The mean dose to the parotid gland were obtained. Patients were evaluated during treatment for acute xerostomia using the RTOG toxicity scoring system as well as in follow up after completion of treatment for evaluation of late xerostomia. The maximum scores for the early and late toxicities were used for this study. Patients were divided into two groups: group 1 with patients with mean parotid dose less than 26 Gy and group 2 with patients with mean parotid dose greater than 26 Gy. A non-parametric correlation and Chi square analysis was performed to determine the relationship between these two groups with the grade of acute and late xerostomia for patients treated using IMRT with and without chemotherapy. The median follow up after completion of radiation treatment is 8 months. Results: The median mean parotid dose for HNC patients treated with IMRT with and without chemotherapy is 26.5 and 25 Gy, respectively (p=NS). For all patients with mean parotid dose less than 26 Gy, rate of Grade 2 and 3 acute salivary toxicity were 20% and 3% compared to 33% and 9%, respectively, for patients with mean parotid dose greater than 26 Gy (p=0.005). The rates of Grade 2 and 3 late salivary toxicity for all patients with mean parotid dose < 26 Gy was 8 and 0%, respectively, compared to 23% and 5% for patients with mean parotid dose > 26 Gy (p <0.0001). The grade 2 and 3 acute salivary for toxicities for patients receiving IMRT alone was 16 and 3%, respectively, while 27 and 6%, respectively for patients receiving IMRT and chemotherapy (p<0.0001). For patients with mean parotid dose < 26 Gy, the grade 3 acute and late salivary toxicity was 0 and 0% for patients who were treated with IMRT alone in contrast to 9% and 0%,respectively for patients receiving IMRT and chemotherapy(p=0.001). For patients with mean parotid dose greater than 26 Gy, the Grade 3 acute and late salivary toxicity was 3 and 6%,respectively, for patients treated with IMRT alone compared to 32% and 4%, respectively, for patients receiving chemotherapy and IMRT (p=0.02). Conclusions: This study suggests that distinct dose volume relationships exists for patients treated with chemoradiation versus radiation alone using IMRT for HNC. Patients who received IMRT and chemotherapy had significantly increased acute and late salivary toxicity regardless of the mean parotid dose. A more detailed characterization of this relationship and evaluation of the NTCP is underway with an expanded cohort of patients in order to establish appropriate parotid dose-volume constraints for patients treated with chemoradiation using IMRT.
Purpose/Objective: Acute mucositis is a common acute toxicity for patients treated with radiation therapy for head and neck cancer (HNC) and is significantly increased when combined with chemotherapy. The purpose of this study is to evaluate the correlation between the dose to the oral cavity and the severity of acute mucositis in HNC patients treated with chemotherapy and IMRT. Materials/Methods: Between April 2002 through September 2004, 70 patients with HNC were treated with IMRT with 5–7 fields using dynamic multileaf collimators. All patients also received combination chemotherapy. Patients underwent a simulation procedure for IMRT treatment planning in a Uni-frame® head immobilization system (MED-TEC Corp, Orange City, IA) and centrally planned on Varian Eclipse (version 6.5) in a distributed cancer network. For each patient, the oral cavity was contoured and the dose volume histogram was evaluated using the Eclipse planning system. The median dose delivered to the primary site was 70 Gy. Throughout radiation treatment, all patients were evaluated on a weekly basis by the radiation oncologist to evaluate acute mucositis using the RTOG toxicity scale. The maximum toxicity score was used for this study. Using SPSS 12.0, a non-parametric correlation analysis was performed between the acute mucositis grade and the percent volume of oral cavity receiving doses higher than 15, 30, 40, 45, 50 Gy (V15,V30,V40,V45,V50). Results: The rates of acute mucositis grades 0, 1, 2, and 3 were 6%, 27%, 51% and 16%, respectively. There was no grade 4 or 5 acute mucositis. The median V15, V30, V40, V45, and V50 were 69%, 61%, 30%, 19% and 10%, respectively. There was a statistically significant correlation between acute mucositis grade (p<0.05) and the V15, 30,40,45 (Table 1) while V50 marginal significance (p=0.06). Conclusions: Dose and volume to the oral cavity significantly correlates to the grade of acute mucositis in patients treated with HNC and chemotherapy. The rates of grade 3–4 of mucositis in this study compares favorably to recent clinical trial data (RTOG 91-11) in patients treated with conventional radiation techniques (43% vs. 16%). Further investigation is warranted to explore the dose volume relationship parameters and normal tissue complication probability (NTCP) for oral cavity. Once found, dose volume constraints could be used for IMRT inverse planning to further reduce the incidence of acute mucositis when chemotherapy is used in conjunction with IMRT. Tabled 1Correlation Analysis of Percent Volume of Oral Cavity Receiving More Than 15,30,40,45,50 Gy with Grade of Acute Oral Mucositis