A novel approach to infectious disease control and radiotherapy risk management.

BACKGROUND: Infectious disease outbreaks have always presented challenges to the operation of healthcare systems. In particular, the treatment of cancer patients within Radiation Oncology often cannot be delayed or compromised due to infection control measures. Therefore, there is a need for a strategic approach to simultaneously managing infection control and radiotherapy risks. PURPOSE: To develop a systematic risk management method that uses mathematical models to design mitigation efforts for control of an infectious disease outbreak, while ensuring safe delivery of radiotherapy. METHODS: A two-stage failure mode and effect analysis (FMEA) approach is proposed to modify radiotherapy workflow during an infectious disease outbreak. In stage 1, an Infection Control FMEA (IC-FMEA) is conducted, where risks are evaluated based on environmental parameters, clinical interactions, and modeling of infection risk. occupancy risk index (ORI) is defined as a metric for infection transmission risk level in each room, based on the degree of occupancy. ORI, in combination with ventilation rate per person (Rp ), is used to provide a broad infection risk assessment of workspaces. For detailed IC-FMEA of clinical processes, infection control failure mode (ICFM) is defined to be any instance of disease transmission within the clinic. Infection risk priority number (IRPN) has been formulated as a function of time, distance, and degree of protective measures. Infection control measures are then systematically integrated into the workflow. Since the workflow is perturbed by infection control measures, there is a possibility of introducing new radiotherapy failure modes or increased likelihood of existing failure modes. Therefore, in stage 2, a conventional radiotherapy FMEA (RT-FMEA) should be performed on the adjusted workflow. RESULTS: The COVID-19 pandemic was used to illustrate stage 1 IC-FMEA. ORI and Rp values were calculated for various workspaces within a clinic. A deep inspiration breath hold (DIBH) CT simulation was used as an example to demonstrate detailed IC-FMEA with ICFM identification and IRPN evaluation. A total of 90 ICFMs were identified in the DIBH simulation process. The calculated IRPN values were found to be progressively decreasing for workflows with minimal, moderate, and enhanced levels of protective measures. CONCLUSION: The framework developed in this work provides tools for radiotherapy clinics to systematically assess risk and adjust workflows during the evolving circumstances of any infectious disease outbreak.

Fuzzy analytic hierarchy process-based risk priority number for risk assessments of commissioning process of a ring gantry LINAC.

PURPOSE: We propose a fuzzy analytic hierarchy process (AHP)-based risk priority number (RPN) method in failure modes and effects analysis (FMEA) to overcome the shortcomings of traditional RPN-based FMEA. Our research group has previously published the FMEA to mitigate the failure modes (FMs) for the commissioning process of a ring gantry LINAC. However, inter-relationships among FMs were observed in high ranked FMs due to a heavy reliance on imaging system. METHODS: Fuzzy AHP was applied to determine relative weights of risk impacts based on inter-relationships among FMs. Since the time sequence dependency is a major factor for risk factors, a hierarchical structure of AHP was used to reflect the directional impacts such as causal influence and feedback loop. Two fuzzy weighted RPNs, called (RPNW and FRPNW , were calculated depending on the input values of severity (S), occurrence (O), and probability of not being detected (D) from the evaluators. The RPNW used numerical values, whereas the fuzzy values were used for FRPNW . Both RPNs were calculated by multiplying the weighted O, S, and D using the fuzzy AHP method. RESULTS: The differences between the two fuzzy RPN rankings are due to inherent fuzzy uncertainty and deviations in O, S, and D values submitted by the evaluators. Considering all results of traditional and fuzzy-based FMEA, the two most highly ranked FMs were identified: errors in determining the non-isocentric SSD and SSD from MV images because of the unique features of the ring gantry LINAC. CONCLUSION: This study has demonstrated the feasibility of the use of a fuzzy AHP-based RPN to perform comprehensive analysis and prioritization of FMs. The risk analysis using fuzzy AHP can be improved and/or refined based on the department's specific workflow and clinical preferences taking various priority weighting approaches into account.

A detailed process map for clinical workflow of a new biology-guided radiotherapy (BgRT) machine.

PURPOSE: Biology-guided radiotherapy (BgRT) is a new external beam radiation therapy modality combining PET-CT with a linear accelerator that has the potential to track and treat one or more tumors in real-time. The use of PET and radiopharmaceutical tracers introduces new processes that are different from the existing treatment processes. In this study, we have developed a process map for the clinical implementation of a prototype BgRT machine. METHODS: A team of 13 members from various radiation therapy disciplines at our institution participated in developing a prospective process map for a prototype BgRT machine. The methodology provided by the AAPM TG 100 report was followed. In particular, the steps unique to the BgRT workflow, using hypofractionated stereotactic body radiation therapy with fluorodeoxyglucose radiolabeled with fluorine-18 (FDG) to guide beam delivery, were analyzed. RESULTS: The multi-disciplinary team in the department of radiation oncology at our institution developed a prospective process map for the clinical BgRT workflow. By focusing on the appropriate level of detail, 15 major subprocesses, 133 steps, and 248 substeps were identified and the process map was agreed upon as being useful, implementable, and manageable. Seventy-four steps from nine subprocesses, 55.6% of the whole process, were analyzed to be the BgRT unique steps. They originate mainly from: (1) acquiring multiple PET images at the BgRT machine with separate patient visits, (2) creating a unique biological treatment volume for BgRT plan (PTVBgRT ), and (3) BgRT plan optimization and treatment delivery using PET images. CONCLUSION: Using BgRT to irradiate multiple metastases in the same session will impact clinical workflow, thus a graphical process map depicting the new clinical workflow with an appropriate level of detail is critical for efficient, safe, and high-quality care. The prospective process map will guide the successful setup and use of the new BgRT system.

Is Halcyon feasible for single thoracic or lumbar vertebral segment SBRT?

PURPOSE: Halcyon linear accelerators employ intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) techniques. The Halcyon offers translational, but not rotational, couch correction, which only allows a 3 degrees of freedom (3-DOF) correction. In contrast, the TrueBeam (TB) linear accelerator offers full 6-DOF corrections. This study aims to evaluate the difference in treatment plan quality for single thoracic or lumbar vertebral segment SBRT between the Halcyon and TB linear accelerators. In addition, this study will also investigate the effect of patient rotational setup errors on the final plan quality. METHODS: We analyzed 20 patients with a single-level spine metastasis located between the T7 and L5 vertebrae near the spinal canal. The median planning target volume was 52.0 cm3 (17.9-138.7 cm3 ). The median tumor diameter in the axial plane was 4.6 cm (range 1.7-6.8 cm), in the sagittal plane was 3.3 cm (range 2-5 cm). The prescription doses were either 12-16 Gy in 1 fraction or 18-24 Gy in 3 fractions. All patients were treated on the TB linear accelerator with a 2.5 mm Multi-Leaf Collimator (MLC) leaf width. Treatment plans were retrospectively created for the Halcyon, which has a 5 mm effective MLC leaf width. The 20 patients had a total of 50 treatments. Analysis of the 50 cone beam computed tomography (CBCT) scans showed average rotational setup errors of 0.6°, 1.2°, and 0.8° in pitch, yaw, and roll, respectively. Rotational error in roll was not considered in this study, as the original TB plans used a coplanar volumetric modulated arc therapy (VMAT) technique, and each 1° of roll will contribute an error of 1/360. If a plan has 3 arcs, the contribution from errors in roll will be < 0.1%. To simulate different patient setup errors, for each patient, 12 CT image datasets were generated in Velocity AI with different rotational combinations at a pitch and yaw of 1°, 2°, and 3°, respectively. We recalculated both the TB and Halcyon plans on these rotated images.  The dosimetric plan quality was evaluated based on the percent tumor coverage, the Conformity Index (CI), Gradient Index (GI), Homogeneity index (HI), the maximum dose to the cord/cauda, and the volume of the cord/cauda receiving 8, 10, and 12 Gy (V8Gy, V10Gy and V12Gy). Paired t-tests were performed between the original and rotated plans with a significance level of 0.05. RESULTS: The Eclipse based VMAT plans on Halcyon achieved a similar target coverage (92.3 ± 3.0% vs. 92.4 ± 3.3%, p = 0.82) and CI (1.0 ± 0.1 vs. 1.1 ± 0.2, p = 0.12) compared to the TB plans. The Gradient index of Halcyon is higher (3.96 ±0.8) than TB (3.85 ±0.7), but not statistically significant. The maximum dose to the spinal cord/cauda was comparable (11.1 ± 2.8 Gy vs. 11.4 ± 3.6 Gy, p = 0.39), as were the V8Gy, V10Gy and V12Gy to the cord/cauda. The dosimetric influence of patient rotational setup error was statistically insignificant for rotations of up to 1° pitch/yaw (with similar target coverage, CI, max cord/cauda dose and V8Gy, V10Gy, V12Gy for cord/cauda). The total number of monitor units (MUs) for Halcyon (4998 ± 1688) was comparable to that of TB (5463 ± 2155) (p = 0.09). CONCLUSIONS: The Halcyon VMAT plans for a single thoracic or lumbar spine metastasis were dosimetrically comparable to the TB plans. Patient rotation within 1° in the pitch and yaw directions, if corrected by translation, resulted in insignificant dosimetric effects. The Halcyon linear accelerator is an acceptable alternative to TB for the treatment of single thoracic or lumbar spinal level metastasis, but users need to be cautious about the patient rotational setup error.  It is advisable to select patients appropriately, including only those with the thoracic or lumbar spine involvement and keeping at least 2 mm separation between the target and the cord/cauda. More margin is needed if the distance between the isocenter and cord/cauda is larger. It is advisable to place the planning isocenter close to the spinal canal to further mitigate the rotational error. SUMMARY: We simulated various scenarios of patient setup errors with different rotational combinations of pitch and yaw with 1°, 2°, and 3°, respectively. Rotation was corrected with translation only to mimic the Halcyon treatment scenario. Using the Halcyon for treating a tumor in a single thoracic or lumbar vertebral segment is feasible, but caution should be noted in patients requiring rotational corrections of > 1° in the absence of 6-DOF correction capabilities.

Assessment of deep inspiration breath hold technique setup reproducibility using mega voltage imaging for left breast cancer radiation therapy-integrated network study.

We evaluated daily setup reproducibility of deep inspiration breath hold (DIBH) using mega voltage (MV) imaging for left breast cancer radiation therapy. Analysis of 109 left breast cancer patients across UPMC Hillman Cancer Center network treated using DIBH technique with daily MV imaging was done. Patient characteristics, MV imaging procedure used and inter-fraction directional shifts were collected. For the statistical analyses, we separated all patients into 2 groups in each of the following 3 categories; (1) obese (BMI ≥ 30) vs nonobese, (2) mastectomy vs lumpectomy, (3) internal mammary node (IMN) treatment vs no IMN treatment. The group mean inter-fraction directional shifts were as following: (1) 0.7 mm (superior), 0.8 mm (inferior); (2) 0.65 mm (left), 0.64 mm (right); (3) 0.89 mm (anterior), 0.83 mm (posterior). Also, any directional shift ≥ 2 mm, ≥ 3 mm, ≥ 4 mm, ≥ 5 mm, ≥ 10 mm was found to be 52.9%, 37.6%, 30.9%, 21.9%, 3.7% of total fractions, respectively. In the stratified analysis, obese patients had larger directional shifts (p < 0.05) and highly associated with number of fractions for ≥ 5 mm in any directional shift compared to nonobese patients (29% vs 17%; p = 0.04). DIBH setup for left breast cancer treatment at our large cancer center network was reproducible with any mean directional shifts less than 1.0 mm using MV imaging. Daily imaging would be more beneficial for obese patients compared to nonobese patients.

Early clinical experience with varian halcyon V2 linear accelerator: Dual-isocenter IMRT planning and delivery with portal dosimetry for gynecological cancer treatments.

PURPOSE: Varian Halcyon linear accelerator version 2 (The Halcyon 2.0) was recently released with new upgraded features. The aim of this study was to report our clinical experience with Halcyon 2.0 for a dual-isocenter intensity-modulated radiation therapy (IMRT) planning and delivery for gynecological cancer patients and examine the feasibility of in vivo portal dosimetry. METHODS: Twelve gynecological cancer patients were treated with extended-field IMRT technique using two isocenters on Halcyon 2.0 to treat pelvis and pelvic/or para-aortic nodes region. The prescription dose was 45 Gy in 25 fractions (fxs) with simultaneous integrated boost (SIB) dose of 55 or 57.5 Gy in 25 fxs to involved nodes. All treatment plans, pretreatment patient-specific QA and treatment delivery records including daily in vivo portal dosimetry were retrospectively reviewed. For in vivo daily portal dosimetry analysis, each fraction was compared to the reference baseline (1st fraction) using gamma analysis criteria of 4 %/4 mm with 90% of total pixels in the portal image planar dose. RESULTS: All 12 extended-field IMRT plans met the planning criteria and delivered as planned (a total of 300 fractions). Conformity Index (CI) for the primary target was achieved with the range of 0.99-1.14. For organs at risks, most were well within the dose volume criteria. Treatment delivery time was from 5.0 to 6.5 min. Interfractional in vivo dose variation exceeded gamma analysis threshold for 8 fractions out of total 300 (2.7%). These eight fractions were found to have a relatively large difference in small bowel filling and SSD change at the isocenter compared to the baseline. CONCLUSION: Halcyon 2.0 is effective to create complex extended-field IMRT plans using two isocenters with efficient delivery. Also Halcyon in vivo dosimetry is feasible for daily treatment monitoring for organ motion, internal or external anatomy, and body weight which could further lead to adaptive radiation therapy.

A 3D correction method for predicting the readings of a PinPoint chamber on the CyberKnife® M6™ machine.

The use of small fields in radiation therapy techniques has increased substantially in particular in stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). However, as field size reduces further still, the response of the detector changes more rapidly with field size, and the effects of measurement uncertainties become increasingly significant due to the lack of lateral charged particle equilibrium, spectral changes as a function of field size, detector choice, and subsequent perturbations of the charged particle fluence. This work presents a novel 3D dose volume-to-point correction method to predict the readings of a 0.015 cc PinPoint chamber (PTW 31014) for both small static-fields and composite-field dosimetry formed by fixed cones on the CyberKnife® M6™ machine. A 3D correction matrix is introduced to link the 3D dose distribution to the response of the PinPoint chamber in water. The parameters of the correction matrix are determined by modeling its 3D dose response in circular fields created using the 12 fixed cones (5 mm-60 mm) on a CyberKnife® M6™ machine. A penalized least-square optimization problem is defined by fitting the calculated detector reading to the experimental measurement data to generate the optimal correction matrix; the simulated annealing algorithm is used to solve the inverse optimization problem. All the experimental measurements are acquired for every 2 mm chamber shift in the horizontal planes for each field size. The 3D dose distributions for the measurements are calculated using the Monte Carlo calculation with the MultiPlan® treatment planning system (Accuray Inc., Sunnyvale, CA, USA). The performance evaluation of the 3D conversion matrix is carried out by comparing the predictions of the output factors (OFs), off-axis ratios (OARs) and percentage depth dose (PDD) data to the experimental measurement data. The discrepancy of the measurement and the prediction data for composite fields is also performed for clinical SRS plans. The optimization algorithm used for generating the optimal correction factors is stable, and the resulting correction factors were smooth in the spatial domain. The measurement and prediction of OFs agree closely with percentage differences of less than 1.9% for all the 12 cones. The discrepancies between the prediction and the measurement PDD readings at 50 mm and 80 mm depth are 1.7% and 1.9%, respectively. The percentage differences of OARs between measurement and prediction data are less than 2% in the low dose gradient region, and 2%/1 mm discrepancies are observed within the high dose gradient regions. The differences between the measurement and prediction data for all the CyberKnife based SRS plans are less than 1%. These results demonstrate the existence and efficiency of the novel 3D correction method for small field dosimetry. The 3D correction matrix links the 3D dose distribution and the reading of the PinPoint chamber. The comparison between the predicted reading and the measurement data for static small fields (OFs, OARs and PDDs) yield discrepancies within 2% for low dose gradient regions and 2%/1 mm for high dose gradient regions; the discrepancies between the predicted and the measurement data are less than 1% for all the SRS plans. The 3D correction method provides an access to evaluate the clinical measurement data and can be applied to non-standard composite fields intensity modulated radiation therapy point dose verification.

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases.

Toxicities Following Stereotactic Ablative Radiotherapy Treatment of Locally-Recurrent and Previously Irradiated Head and Neck Squamous Cell Carcinoma.

Stereotactic ablative radiotherapy (SABR) with concomitant cetuximab is an effective treatment option for previously irradiated, locally recurrent squamous cell carcinoma of the head and neck. Its local control and overall survival are similar to those of other available treatment options. Each retreatment depends heavily on the prior treatment and every patient is a special case. Based on the experience of our institution and previously published studies, for patients who receive concomitant cetuximab with a median prior radiation therapy dose of 70Gy, we recommend a total dose of 40-44Gy delivered in 5 fractions on alternating days over 1-2 weeks. However, Grade 2 or 3 toxicities are not uncommon. Therefore, in this review, we also report a pilot study that applies a normal tissue complication probability dose-response model to estimate the probability of toxicities in locally recurrent squamous cell carcinoma of the head and neck reirradiated with SABR. Although this dose-response model includes concurrent targeted therapy and no comparable model yet exists for SABR without it, complication rates without concurrent biological therapy or chemotherapy should be no higher than those described here.

Treatment Plan Technique and Quality for Single-Isocenter Stereotactic Ablative Radiotherapy of Multiple Lung Lesions with Volumetric-Modulated Arc Therapy or Intensity-Modulated Radiosurgery.

The aim of this study is to provide a practical approach to the planning technique and evaluation of plan quality for the multi-lesion, single-isocenter stereotactic ablative radiotherapy (SABR) of the lung. Eleven patients with two or more lung lesions underwent single-isocenter volumetric-modulated arc therapy (VMAT) radiosurgery or IMRS. All plans were normalized to the target maximum dose. For each plan, all targets were treated to the same dose. Plan conformity and dose gradient were maximized with dose-control tuning structures surrounding targets. For comparison, multi-isocenter plans were retrospectively created for four patients. Conformity index (CI), homogeneity index (HI), gradient index (GI), and gradient distance (GD) were calculated for each plan. V5, V10, and V20 of the lung and organs at risk (OARs) were collected. Treatment time and total monitor units (MUs) were also recorded. One patient had four lesions and the remainder had two lesions. Six patients received VMAT and five patients received intensity-modulated radiosurgery (IMRS). For those treated with VMAT, two patients received 3-arc VMAT and four received 2-arc VMAT. For those treated with IMRS, two patients were treated with 10 and 11 beams, respectively, and the rest received 12 beams. Prescription doses ranged from 30 to 54 Gy in three to five fractions. The median prescribed isodose line was 84% (range: 80-86%). The median maximum dose was 57.1 Gy (range: 35.7-65.1 Gy). The mean combined PTV was 49.57 cm(3) (range: 14.90-87.38 cm(3)). For single-isocenter plans, the median CI was 1.15 (range: 0.97-1.53). The median HI was 1.19 (range: 1.16-1.28). The median GI was 4.60 (range: 4.16-7.37). The median maximum radiation dose (Dmax) to total lung was 55.6 Gy (range: 35.7-62.0 Gy). The median mean radiation dose to the lung (Dmean) was 4.2 Gy (range: 1.1-9.3 Gy). The median lung V5 was 18.7% (range: 3.8-41.3%). There was no significant difference in CI, HI, GI, GD, V5, V10, and V20 (lung, heart, trachea, esophagus, and spinal cord) between single-isocenter and multi-isocenter plans. This multi-lesion, single-isocenter lung SABR planning technique demonstrated excellent plan quality and clinical efficiency and is recommended for radiosurgical treatment of two or more lung targets for well-suited patients.

Clinical implementation of tangential field intensity modulated radiation therapy (IMRT) using sliding window technique and dosimetric comparison with 3D conformal therapy (3DCRT) in breast cancer.

The purpose of this study was to evaluate the clinical implementation of tangential field IMRT using sliding window technique and to compare dosimetric parameters with 3-dimensional conformal radiation therapy (3DCRT). Twenty breast cancer patients were randomly selected for comparison of intensity modulated radiation therapy (IMRT)-based treatment plan with 3DCRT. Inverse treatment was performed using the sliding window technique, employing the Eclipse Planning System (version 7.1.59, Varian, Palo Alto, CA). The dosimetric parameters compared were V(95) (the percentage of target volume getting > or =95% of prescribed dose), V(105), V(110), and dose homogeneity index, DHI (percentage of target volume getting between 95% and 110% of prescribed dose). The mean V(95), DHI, V(105), and V(110) for target volume for IMRT vs. 3D were 90.6% (standard deviation [SD]: 3.2) vs. 91% (SD: 3.0), 87.7 (SD: 6.0) vs. 82.6 (SD: 7.8), 27.3% (SD: 20.3) vs. 49.4% (SD: 14.3), and 2.8 (SD: 5.6) vs. 8.4% (SD: 7.4), respectively. DHI was increased by 6.3% with IMRT compared to 3DCRT (p < 0.05). The reductions of V(105) and V(110) for the IMRT compared to 3DCRT were 44.7% and 66.3%, respectively (p < 0.01). The mean dose and V(30) for heart with IMRT were 2.3 (SD: 1.1) and 1.05 (SD: 1.5) respectively, which was a reduction by 6.8% and 7.9%, respectively, in comparison with 3D. Similarly, the mean dose and V(20) for the ipsilateral lung and the percentage of volume of contralateral volume lung receiving > 5% of prescribed dose with IMRT were reduced by 9.9%, 2.2%, and 35%, respectively. The mean of total monitor units used for IMRT and 3DCRT was about the same (397 vs. 387). The tangential field IMRT for intact breast using sliding window technique was successfully implemented in the clinic. We have now treated more than 1000 breast cancer patients with this technique. The dosimetric data suggest improved dose homogeneity in the breast and reduction in the dose to lung and heart for IMRT treatments, which may be of clinical value in potentially contributing to improved cosmetic results and reduced late treatment-related toxicity.

Analysis of organ motion effects on the effective fluences for liver IMRT.

An effective fluence concept was employed to make forward dose calculations to investigate the effects of a distorted fluence map on dose plans. Fluence changes caused by organ motion were calculated using Chui's algorithm (2003 Med. Phys. 30 1736). In two test cases with various fluence maps, the effects of motion were simulated using a maximal displacement from 5 mm to 25 mm; 108 fluence maps that were calculated from 16 IMRT plans for eight liver cancer patients were analyzed and compared with and without gating. Fluoroscopic measurements were made of a moving diaphragm in this study. Fluence changes associated with superior-inferior organ motion, perpendicular to the moving MLC, were also examined. The effects of motion on the fluence maps were evaluated from both the fluence differences between static and motion and the chi function. The maximum displacements of the organs in all of these cases were analyzed and correlated with the change in fluence generated from the liver IMRT plans. The dosimetric effects on the target coverage were evaluated for each plan. The results indicate that, for the same fluence map, the mean fluence intensity error or the percentage of the fluence points that have an unacceptable error is linearly related to the extent of motion. For different fluence maps, the degree to which the fluence is distorted by motion is strongly related to the product of the motion extent and the fluence gradient in the direction of diaphragm motion. For eight liver patients and 16 IMRT plans in this work (with gated technique, motion extent from 0.5 cm to 1.0 cm; without gated technique, motion extent from 0.9 cm to 1.8 cm), the fluence modulations are mild, such that the respiratory motion of each patient did not strongly affect the CTV coverage. The mean dose error is 1.5% for free motion (0.9-1.8 cm) and is around 1% for gated motion (0.5-1 cm).

Early clinical outcome with concurrent chemotherapy and extended-field, intensity-modulated radiotherapy for cervical cancer.

PURPOSE: To assess the early clinical outcomes with concurrent cisplatin and extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix. METHODS AND MATERIALS: Thirty-six patients with Stage IB2-IVA cervical cancer treated with EF-IMRT were evaluated. The pelvic lymph nodes were involved in 19 patients, and of these 19 patients, 10 also had para-aortic nodal disease. The treatment volume included the cervix, uterus, parametria, presacral space, upper vagina, and pelvic, common iliac, and para-aortic nodes to the superior border of L1. Patients were assessed for acute toxicities according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. All late toxicities were scored with the Radiation Therapy Oncology Group late toxicity score. RESULTS: All patients completed the prescribed course of EF-IMRT. All but 2 patients received brachytherapy. Median length of treatment was 53 days. The median follow-up was 18 months. Acute Grade > or = 3 gastrointestinal, genitourinary, and myelotoxicity were seen in 1, 1, and 10 patients, respectively. Thirty-four patients had complete response to treatment. Of these 34 patients, 11 developed recurrences. The first site of recurrence was in-field in 2 patients (pelvis in 1, pelvis and para-aortic in 1) and distant in 9 patients. The 2-year actuarial locoregional control, disease-free survival, overall survival, and Grade > or = 3 toxicity rates for the entire cohort were 80%, 51%, 65%, and 10%, respectively. CONCLUSION: Extended-field IMRT with concurrent chemotherapy was tolerated well, with acceptable acute and early late toxicities. The locoregional control rate was good, with distant metastases being the predominant mode of failure. We are continuing to accrue a larger number of patients and longer follow-up data to further extend our initial observations with this approach.

The potential nephrotoxic effects of intensity modulated radiotherapy delivered to the para-aortic area of women with gynecologic malignancies: preliminary results.

OBJECTIVE: To assess kidney function via creatinine clearance before and after radiotherapy in gynecologic cancer patients treated to the para-aortic (PA) area via Intensity Modulated Radiotherapy (IMRT). METHODS: Twenty-three patients underwent IMRT to the para-aortic area, were followed for at least 5 months, and had the necessary laboratory data to calculate creatinine clearance. Various patient-related factors and radiotherapy-treatment related factors were analyzed to determine their association with changes in CrCl. RESULTS: Median follow-up was 10.9 months (range, 5-19 months). Median patient age was 51.7 years (range, 22-78). The average initial CrCl was noted to be 109.23 mL/min (range, 38.64-188.38) before radiotherapy and decreased to 90.00 mL/min (29.31-175.61) after radiotherapy (P = 0.004). Although 17 patients had a decrease in their CrCl, 6 were found to have a slight elevation. Five factors were associated with a decrement in CrCl greater than the average decrease (17.6%): presence of hydronephrosis, age <50, no history of cisplatin treatment, a BED to gross adenopathy exceeding mean BED, and salvage treatment of PA node recurrence. Subgroup analysis revealed that the only statistically significant change within the group of patient and/or treatment-related factors was between patients who were <50-year-old and patients who were > or =50 years of age (P = 0.03). No patient exhibited clinical signs of radiation-induced nephropathy. CONCLUSION: With a median follow-up of 10.9 months, the estimated CrCl decreased by 17.6% after IMRT to the para-aortic area +/- cisplatin chemotherapy. The greatest decrease in CrCl occurred in patients who had a history of hydronephrosis. Subgroup analysis revealed that the decline in CrCl was significantly greater for patients younger than 50 years of age. Interestingly, a greater decline in CrCl was noted for those patients who did not have a history of cisplatin treatment. Our preliminary results indicate that IMRT +/- cisplatin chemotherapy to the para-aortic area of women is safe and is not associated with any clinical sequelae of renal toxicity despite a small decrement in CrCl in most, but not all patients.

Feasibility of concurrent cisplatin and extended field radiation therapy (EFRT) using intensity-modulated radiotherapy (IMRT) for carcinoma of the cervix.

OBJECTIVES: To assess the acute tolerance of delivering concurrent cisplatin and extended field radiotherapy (EFRT) using intensity-modulated radiotherapy technique (IMRT) for cancer of the cervix. METHODS: All patients receiving definitive treatment for cervical cancer were treated with EFRT using IMRT technique and concurrent cisplatin. The treatment volume included the cervix, uterus, parametria, presacral space, upper vagina, pelvic, common iliac, and paraaortic nodes to the top of L1. All regions received 45 Gy (25 fractions) with a simultaneous boost to involved nodes (55 Gy/25 fractions). Patients were assessed weekly for toxicity and response. RESULTS: Twenty-two consecutive patients underwent treatment. All patients completed the prescribed course of EFRT. Median treatment length was 39.5 days (range 36-53). Treatment breaks of 2 and 3 days were required for bone marrow toxicity in 2 patients. The final week of chemotherapy was held in 2 patients because of neutropenia. No patient suffered acute or subacute grade 3 or 4 GI or GU toxicity. CONCLUSION: In this clinical study, an IMRT technique was used to successfully deliver EFRT with concurrent chemosensitization for cervical cancer. The technique was associated with an acceptable acute toxicity without significant treatment protraction. This new role for IMRT merits further evaluation with larger patient numbers and longer follow-up.