Total Prescription Dose Research Articles

Assessing the impact of distortion correction on Gamma Knife radiosurgery for multiple metastasis: Volumetric and dosimetric analysis

IntroductionMagnetic resonance imaging (MRI) is a robust neuroimaging technique and is the preferred method for stereotactic radiosurgery (SRS) planning. However, MRI data always contain distortions caused by hardware and patient factors. Research questionCan these distortions potentially compromise the effectiveness and safety of SRS treatments? Material and methodsTwenty-six MR datasets with multiple metastatic brain tumors (METs) used for Gamma Knife radiosurgery (GKRS) were retrospectively evaluated. A commercially available software was used for distortion correction. Geometrical agreement between corrected and uncorrected tumor volumes was evaluated using MacDonald criteria, Euclidian distance, and Dice similarity coefficient (DSC). SRS plans were generated using uncorrected tumor volumes, which were assessed to determine their coverage of the corrected tumor volumes. ResultsThe median target volume was 0.38 cm3 (range,0.01–12.38 cm3). A maximum displacement of METs of up to 2.87 mm and a median displacement of 0.55 mm (range,0.1–2.87 mm) were noted. The median DSC between uncorrected and corrected MRI was 0.92, and the most concerning case had a DSC of 0.46. Although all plans met the optimization criterion of at least 98% of the uncorrected tumor volume (median 99.55%, range 98.1–100%) receiving at least 100% of the prescription dose, the percent of the corrected tumor volume receiving the total prescription dose was a median of 95.45% (range,23.1–99.5%). Discussion and conclusionMRI distortion, though visually subtle, has significant implications for SRS planning. Regular utilization of corrected MRI is recommended for SRS planning as distortion is sometimes enough to cause a volumetric miss of SRS targets.

Stereotactic Body Radiation Therapy for Large Volume Solid Tumor Spinal Metastases Involving Three or More Contiguous Vertebral Levels

Data for treating 3 or more contiguous vertebral bodies with SBRT is limited. The purpose of this study was to explore oncologic outcomes and toxicity of spine SBRT delivered to large volume solid tumor metastases involving 3 or more contiguous vertebral levels. Patients treated with spine SBRT for vertebral metastases involving 3 or more contiguous levels between 2009 and 2021 were retrospectively reviewed. Data on demographics, dosimetry, toxicity, and outcomes were collected. Radiographic local failure was defined as progressive disease on CT and/or MRI in the treatment volume compared to the pre-SBRT baseline. Local control (LC) and overall survival (OS) were calculated from end of SBRT using the Kaplan-Meier and log-rank test. A total of 141 patients were included with a median follow-up of 9.7 months. The majority of patients had either 3 (74%) or 4 (16%) involved contiguous vertebral levels. Twenty-two percent, 57%, 14%, and 7% of treated lesion began in the cervical, thoracic, lumbar, and sacral vertebral levels, respectively. The most common primary sites were NSCLC (15.6%), kidney (14.9%), and breast (13.5%). Thirty-two percent of patients had prior external beam radiation to the same vertebral level, 63% had prior surgery, and 43% had prior vertebral fracture. Paraspinal extension was identified in 26% at time of SBRT. Median pre-SBRT Bilsky grade was 2 (range 0-3). The median total prescription dose was 27 Gy (range: 12-43 Gy) with the most common dose (Gy)/fractionation schedules of 27/5 (32%), 30/5 (25%), and 25/5 (18%). The median Dmax was 4727 cGy (range 2070-7857) with a median prescription isodose of 58% (range 48-97). The median OS was 12.4 months (95% CI 9.6-15.3). 1- and 2- year OS were 51% and 35%, respectively. Local progression occurred across all histologies, most commonly in colon and NSCLC (16.7%). 1- and 2-year LC were 70% and 57%, respectively. In the radiation-naïve cohort, 1- and 2-year LC were 75% and 63%, respectively and 52% and 34% in the prior radiation group with no statistically significant difference in time to local progression (p = 0.075). There was no statistically significant difference in LC when comparing 3 versus 4 or more contiguous lesions (p = 0.66). Forty percent of patients that progressed underwent salvage treatment (58% surgery, 33% SBRT, 8% systemic therapy). Post-SBRT vertebral compression fracture rate was 11.6%. We present the largest series to date of patients treated with SBRT for large volume spinal metastases involving 3 or more contiguous levels. These data suggest reasonable local control and low toxicity with SBRT; therefore, SBRT should be considered a practical modality to offer this cohort.

Optimal laboratory testing protocol for patients with acne taking oral isotretinoin

Isotretinoin is a widely prescribed drug for various dermatological conditions, especially acne. Blood tests are routinely performed to monitor its side effects. However, the optimal testing schedule remains controversial. To evaluate the laboratory monitoring tests and schedules of patients with acne taking isotretinoin to determine the most efficient testing regimen. We retrospectively reviewed electronic medical records from the Dermatology Department of Dongguk University Ilsan Hospital from 2005 to 2020 for patients prescribed isotretinoin for acne who underwent monthly blood tests. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and triglyceride (TG) levels significantly changed between 5 and 6 mo when the total prescription period and dose variables were considered altogether. The high-density lipoprotein level also significantly changed between 5 and 6 mo. However, low-density lipoprotein (LDL) and total cholesterol levels significantly changed between 1 and 2 mo. We recommend testing AST, ALT, and TG levels once every 5 to 6 mo. We also suggest testing LDL and total cholesterol levels during the first and second months.

Feature Analysis of Predictors Affecting the Nidus Obliteration of Linear Accelerator-Based Radiosurgery for Arteriovenous Malformations Using Explainable Predictive Modeling

This study aimed to evaluate prognostic factors associated with nidus obliteration following stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations. From January 2001 to January 2018, 119 patients who underwent SRS with AVM were studied to analyze major prognostic factors (age, prescription dose (Gy), volume (mm3), nidus size (cm), and Spetzler–Martin (SM) grade) for nidus obliteration. A random forest and tree explainer was used to construct a predictive model of nidus obliteration. The prognostic factors affecting nidus obliteration from most to least important were age, nidus size, volume, total prescription dose, and SM grade, using a predictive model. In a specific case for nidus size (1.5 cm), total dose (23 Gy), and SM grade (2), the result showed a high obliteration score of 0.75 with the actual obliteration period of 6 months spent; the mean AUC was 0.90 in K-fold cross validation. The predictive model identified the main contributing factors associated with a prognostic of nidus obliteration from linear accelerator-based SRS for cerebral AVM. It was confirmed that the results, including the prognostic factors, are potentially useful for outcome prediction for patient and treatment.

Fraction optimization for hybrid proton-photon treatment planning.

Hybrid proton-photon radiotherapy (RT) can provide better plan quality than proton or photon only RT, in terms of robustness of target coverage and sparing of organs-at-risk (OAR). This work develops a hybrid treatment planning method that can optimize the number of proton and photon fractions as well as proton and photon plan variables, so that the hybrid plans can be clinically delivered day-to-day using either proton or photon machine. In the new hybrid treatment planning method, the total dose distribution (sum of proton dose and photon dose) is optimized for robust target coverage and optimal OAR sparing, by jointly optimizing proton spots and photon fluences, while the target dose uniformity is also enforced individually on both proton dose and photon dose, so that the hybrid plans can be separately and robustly delivered on proton or photon machine. To ensure the target dose uniformity for proton and photon plans, the number of proton and photon fractions is explicitly modeled and optimized, so that the target dose for proton and photon dose components is constrained to be a constant fraction of the total prescription dose while the plan quality based on total dose is optimized. The feasibility of hybrid planning using the proposed method is validated with representative clinical cases including abdomen, lung, head-and-neck (HN), and brain. For all cases, hybrid plans provided better overall plan quality and OAR sparing than proton-only or photon-only plans, better target dose uniformity and robustness than proton-only plans, quantified by treatment planning objectives and dosimetric parameters. Moreover, for HN and brain cases, hybrid plans also had better target coverage than photon-only plans. We have developed a new hybrid treatment planning method that optimizes number of proton and photon fractions as well as proton spots and photon fluences, for generating hybrid plans that can be separately and robustly delivered on proton or photon machines. Preliminary results have demonstrated that hybrid plans generated by the new method have better plan quality than proton-only or photon-only plans.

Hybrid Proton-Photon Treatment Planning with Fraction Optimization

<h3>Purpose/Objective(s)</h3> Hybrid proton-photon radiotherapy (RT) can provide better plan quality than proton or photon only RT, in terms of robustness of target coverage and sparing of organs-at-risk (OAR). This work develops a hybrid treatment planning method that can optimize the number of proton and photon fractions as well as proton and photon plan variables, so that the hybrid plans can be clinically delivered day-to-day using either proton or photon machine. <h3>Materials/Methods</h3> In the new hybrid treatment planning method, the total dose distribution (sum of proton dose and photon dose) is optimized for robust target coverage and optimal OAR sparing, by jointly optimizing proton spots and photon fluences, while the target dose uniformity is also enforced individually on both proton dose and photon dose, so that the hybrid plans can be separately and robustly delivered on proton or photon machine. To ensure the target dose uniformity for proton and photon plans, the number of proton and photon fractions is explicitly modeled and optimized, so that the target dose for proton and photon dose components is constrained to be a constant fraction of the total prescription dose while the plan quality based on total dose is optimized. The feasibility of the generation of clinically deliverable hybrid plans using the proposed method is validated with representative clinical cases including abdomen, lung, head-and-neck (HN), and brain. <h3>Results</h3> For all cases, hybrid plans provided better overall plan quality and OAR sparing than proton-only or photon-only plans, better target dose uniformity and robustness than proton-only plans, quantified by treatment planning objectives and dosimetric parameters. Moreover, for HN and brain cases, hybrid plans also had better target coverage than photon-only plans. <h3>Conclusion</h3> We have developed a new hybrid treatment planning method that optimizes number of proton and photon fractions as well as proton spots and photon fluences, for generating clinically deliverable hybrid plans that can be separately and robustly delivered on proton or photon machines. Preliminary results have demonstrated that hybrid plans generated via the new method have better plan quality than proton-only or photon-only plans.

Impact of intrafraction changes in delivered dose of the day for prostate cancer patients treated with stereotactic body radiotherapy via MR-Linac.

The purpose of this study is to evaluate the impact of intrafraction pelvic motion by comparing the adapted plan dose (APD) and the computed delivered dose of the day (DDOTD) for patients with prostate cancer (PCa) treated with SBRT on the MR-Linac. Twenty patients with PCa treated with MR-guided adaptive SBRT were included. A 9-field IMRT distribution was adapted based on the anatomy of the day to deliver a total prescription dose of 3000cGy in 5 fractions to the prostate plus a 5mm isotropic margin. Prostate, bladder, and rectum were re-contoured on the MR-image acquired during treatment delivery (MRBO). DDOTD was computed by propagating the dose from the daily adapted plan generated during treatment onto the MRBO. Target coverage was met for all fractions, however, computed DDOTD was significantly less than the APD (p<0.05). During an average treatment of 53min, mean bladder volume increased by 116%, which led to a significant decrease in the DDOTD bladder D40% (p<0.001). However, DDOTD to bladder 5cc was significantly higher (p<0.001) than APD. Rectum intrafraction changes were observed based on a volume change of -20% to 83% and presence of significant dose changes from APD to DDOTD for rectum D20% (p<0.05) and D1cc (p<0.0001). Intrafraction motion observed during prostate SBRT treatment on the MR-Linac have dosimetric impacts on both the target and organs at risk. Post-treatment computation using DDOTD may inform adaptation beyond anatomic changes in subsequent treatment fractions to best capitalize on MR-Linac technology and widen the therapeutic index of SBRT for PCa.

Staged radiosurgery alone versus postoperative cavity radiosurgery for patients with midsize-to-large brain metastases: a propensity score matching analysis.

The authors investigated and compared the results of staged stereotactic radiosurgery (S-SRS) alone and those of postoperative cavity SRS (C-SRS) for patients with midsize-to-large brain metastases (BMs). Patients with BMs who had undergone S-SRS or C-SRS during the period from 2010 to 2020 were retrospectively identified from an institutional database. The two treatment groups were generated by propensity score matching (PSM; match ratio 2:1) based on 13 potential prognostic covariates: sex, age, Karnofsky Performance Status, type of primary cancer, timing of BM diagnosis, extracranial disease status, driver mutations, molecular target therapy, neurological symptoms, number of BMs, location of BMs treated with S-SRS or C-SRS, maximal tumor or cavity volume, and cumulative intracranial tumor volume. Patient survival and control of intracranial disease were compared between the S-SRS and C-SRS groups using time-dependent analyses taking into account competing events. In total, 110 patients in the S-SRS group and 62 in the C-SRS group were selected by PSM. In the S-SRS group, the median interval between the two radiosurgical sessions was 21 days, and the median total prescription dose was 28 Gy at 50%. In the C-SRS group, the median time from surgery to C-SRS was 16 days, and the median prescription dose delivered to the surgical cavity was 15 Gy at 55%. At the time point of data set fixation, 129 patients had died, 43 were alive, and none had been lost to follow-up. The 2-year survival rates for the S-SRS and C-SRS groups after the initial intervention were 33% and 37% and the median survival times were 14.8 and 17.5 months, respectively (p = 0.33). The 2-year cumulative neurological mortality rates were 11% and 9%, respectively (p = 0.65). The 2-year local failure rates were 32% and 12% (p = 0.036) and the 2-year distant recurrence rates were 55% and 58%, respectively (p = 0.53). The 2-year leptomeningeal disease development rates were 9% and 25%, respectively (p = 0.007). The present study revealed no significant difference in overall survival or cumulative neurological mortality between the S-SRS and C-SRS groups. The local control failure rate was significantly higher in the S-SRS group, whereas the incidence of leptomeningeal disease development was significantly higher in the C-SRS group.

Nation-Wide Analysis of Glaucoma Medication Prescription in Fiscal Year of 2019 in Japan.

To report the updated prescription trend of antiglaucoma medications, the dose-based prescription of a glaucoma medication in Japan in the fiscal year 2019 was aggregated by using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open data. Of the 100 most frequently prescribed topical medications for outpatients from out-hospital pharmacies, 32 glaucoma medications were identified. This year, 150.8 million ml of glaucoma medications prescribed accounted for 12.3% of the total prescription dose (1.3 billion ml). The dose was the largest with prostaglandin FP2α agonist (PGF2α), followed by the fixed-dose combination (FDC) of β-blocker and carbonic anhydrase inhibitor (β + CAI) and α2-agonist. Prescription doses peaked at 75–79 years old for all medication classes, except for prostaglandin EP2 agonist of that peaked 10 years younger age class than other medications. The prescription dose was larger in women (55.3%) than men (44.7%), single medication formulation (71.2%) than FDC (28.8%), and brand-name (85.2%) than generic (14.8%). By multivariate analysis, prescription doses were affected by roles of the sex (p = 0.0066) and brand-name or generic (p = 0.032), but not by single medication formulation or FDC (p = 0.67); age was the most remarkable parameter for the difference in prescription dose (p < 0.0001). Dose-based anti-glaucoma medication prescription was analyzed using the government-provided most recent database on a national scale. The results provide the up-to-date real-world glaucoma medication prescriptions where the country has the highest aging rate in the world.

Radiomic modeling to predict risk of vertebral compression fracture after stereotactic body radiation therapy for spinal metastases.

In the treatment of spinal metastases with stereotactic body radiation therapy (SBRT), vertebral compression fracture (VCF) is a common and potentially morbid complication. Better methods to identify patients at high risk of radiation-induced VCF are needed to evaluate prophylactic measures. Radiomic features from pretreatment imaging may be employed to more accurately predict VCF. The objective of this study was to develop and evaluate a machine learning model based on clinical characteristics and radiomic features from pretreatment imaging to predict the risk of VCF after SBRT for spinal metastases. Vertebral levels C2 through L5 containing metastases treated with SBRT were included if they were naive to prior surgery or radiation therapy, target delineation was based on consensus guidelines, and 1-year follow-up data were available. Clinical features, including characteristics of the patient, disease, and treatment, were obtained from chart review. Radiomic features were extracted from the planning target volume (PTV) on pretreatment CT and T1-weighted MRI. Clinical and radiomic features selected by least absolute shrinkage and selection operator (LASSO) regression were included in random forest classification models, which were trained to predict VCF within 1 year after SBRT. Model performance was assessed with leave-one-out cross-validation. Within 1 year after SBRT, 15 of 95 vertebral levels included in the analysis demonstrated new or progressive VCF. Selected clinical features included BMI, performance status, total prescription dose, dose to 99% of the PTV, lumbar location, and 2 components of the Spine Instability Neoplastic Score (SINS): lytic tumor character and spinal misalignment. Selected radiomic features included 5 features from CT and 3 features from MRI. The best-performing classification model, derived from a combination of selected clinical and radiomic features, demonstrated a sensitivity of 0.844, specificity of 0.800, and area under the receiver operating characteristic (ROC) curve (AUC) of 0.878. This model was significantly more accurate than alternative models derived from only selected clinical features (AUC = 0.795, p = 0.048) or only components of the SINS (AUC = 0.579, p < 0.0001). In the treatment of spinal metastases with SBRT, a machine learning model incorporating both clinical features and radiomic features from pretreatment imaging predicted VCF at 1 year after SBRT with excellent sensitivity and specificity, outperforming models developed from clinical features or components of the SINS alone. If validated, these findings may allow more judicious selection of patients for prophylactic interventions.

Predictors of Severe Chemoradiation-Related Lymphopenia in Patients With Anal Squamous Cell Carcinoma

Treatment-related lymphopenia may be prognostic for poorer survival in anal squamous cell carcinoma (ASCC). With current randomized trials evaluating the potential role of immunotherapy in localized ASCC, the contribution of host immunity will become increasingly important. We sought to identify clinical, tumor, and dosimetric predictors for severe lymphopenia during chemoradiation (CRT) for ASCC.Patients who underwent CRT for ASCC from 2008-2020 at two Comprehensive Cancer Centers were identified and charts were reviewed. Only those who received 5-fluorouracil and mitomycin C concurrent with IMRT to 50.4-59.4 Gy were included. Lymphopenia was graded per CTCAE v5.0 with absolute lymphocyte count (ALC) nadir < 0.2×109/L indicating grade 4 toxicity. Logistic regression was used to distinguish the effects directly attributable to radiation exposure from contextual covariates. The outcome was presence of grade 4 lymphopenia. The primary predictors of interest were iliac crest V40 and total prescription dose (TPD). It was hypothesized that higher iliac crest V40 and higher TPD would be positively associated with severe lymphopenia. PTV total volume (PTVtv) and GTVp volume were also included and interactions with dose were examined for each. Lastly, covariates included history of malignancy, age, and pre-treatment ALC. These variables were selected because literature has identified them as relevant to lymphopenia in other samples.A total of 119 patients were identified with a median age of 59 years. Forty-seven patients (39%) had T3/4 disease and 57 patients (49%) had node positive disease. Fifty-eight patients (49%) developed grade 4 lymphopenia during CRT or within 1 month of completing treatment. On multivariate analysis pre-treatment ALC (P = 0.006, OR = 0.31), GTVp volume (P = 0.010, OR = 1.23), and iliac crest V40 (P = 0.013, OR = 1.08) were predictive of grade 4 lymphopenia. History of previous malignancy was associated with reduced risk of grade 4 lymphopenia (P = 0.030, OR = 0.04). TPD and PTVtv were not independently predictive of grade 4 lymphopenia, though patients with a higher TPD and smaller PTVtv were significantly more likely to develop grade 4 lymphopenia (P = 0.038) compared to those with both high TPD and PTVtv or both low TPD and PTVtv.Severe lymphopenia is common during CRT for ASCC and certain patients are at higher risk for developing this treatment-related toxicity. Pre-treatment lymphocyte count, larger tumor volume, and dose to the iliac crests are each independent predictors of grade 4 lymphopenia. Additionally, closer observation should be employed when treating patients with higher prescription doses and smaller PTV total volumes. With ongoing efforts to incorporate immunotherapy in the treatment of ASCC, using predictors to detect patients at risk for severe lymphopenia will be increasingly important.

Patterns of local residual disease and local failure after intensity modulated/image guided radiation therapy for sinonasal tumors in dogs

BackgroundMost dogs with sinonasal tumors (SNT) treated with radiation therapy (RT) died because of local disease progression.Hypothesis/ObjectivesOur hypothesis is that the majority of local failure and residual disease would occur within the radiation field.AnimalsTwenty‐two dogs with SNT treated with RT.MethodsRetrospective cohort study. Inclusion criteria: dogs with SNT receiving 10 daily fractions of 4.2 Gy with intensity modulated radiation therapy (IMRT)/image guided radiation therapy (IGRT) and follow‐up cone beam computed tomography (CBCT). Each CBCT was registered with the original radiation planning CT and the gross tumor volume (GTV) contoured. The GTV was classified as residual (GTVr) or a failure (GTVf). The dose statistic for each GTV was calculated with the original IMRT plan. For GTVf, failures were classified as “in‐field,” “marginal,” or “out‐field” if at least 95, 20‐95, or less than 20% of the volume of failure was within 95% (D95) of the total prescription dose, respectively.ResultsThere were 52 follow‐up CBCT/CTs. Overall there was a GTVr for 20 dogs and GTVf for 16 dogs. The majority of GTVr volume was within the original GTV. GTVf analysis showed that 75% (12/16) were “in‐field,” 19% (3/16) were “marginal” and 6% (1/16) were “out‐field.”Conclusion and Clinical ImportanceIn‐field failures are the main pattern for local recurrence, and there is evidence of radioresistant subvolumes within the GTV.

Dosimetric evaluation of whole-pelvis radiation therapy of prostate cancers: clinical experience

AbstractBackground:The standard treatment modalities for prostate cancer include surgery, chemotherapy, hormonal therapy and radiation therapy or any combination depending on the stage of the tumour. Radiation therapy is a common and effective treatment modality for low-intermediate-risk patients with localised prostate cancer, to treat the intact prostate and seminal vesicles or prostate bed post prostatectomy. However, for high-risk patients with lymph node involvement, treatment with radiation will usually include treatment of the whole pelvis to cover the prostate and seminal vesicles or prostate bed and the pelvic lymph nodes followed by a boost delivery dose to the prostate and seminal vesicles or prostate bed.Materials and Methods:We retrospectively analysed the treatment plans for 179 prostate cancer patients treated at the cancer centre with the volumetric-modulated arc therapy (VMAT) technique via RapidArc using 6 MV photon beam. Patients were either treated with a total prescription dose of 78 Gy in 39 fractions for patients with intact prostate or 66 Gy in 33 fractions for post prostatectomy patients.Results:There were 114 (64%) patients treated with 78 Gy/39 and 65 (36%) treated with 66 Gy/34. The mean homogeneity index (HI), conformity index (CI) and uniformity index (UI) for the PTV-primary of patients treated with 78 Gy are 0.06 ± 0.01, 1.04 ± 0.01 and 0.99 ± 0.01, respectively, and the corresponding mean values for patients treated with 66 Gy are 0.06 ± 0.02, 1.05 ± 0.01 and 0.99 ± 0.01, respectively. The mean PTV-primary V95%, V100% and V105% are 99.5 ± 0.5%, 78.8 ± 12.2% and 0.1 ± 0.5%, respectively, for patients treated with 78 Gy and 99.3 ± 0.9%, 78.1 ± 10.6% and 0.1 ± 0.4%, respectively, for patients treated with 66 Gy. The rectal V50Gy, V65Gy, V66.6Gy, V70Gy, V75Gy and V80Gy are 26.8 ± 9.1%, 14.2 ± 5.3%, 13.1 ± 5.0%, 10.8 ± 4.3%, 6.9 ± 3.1% and 0.1 ± 0.1%, respectively, for patients treated with 78 Gy and 33.7 ± 8.4%, 14.1 ± 4.5%, 6.7 ± 4.5%, 0.0 ± 0.2%, 0.0% and 0.0%, respectively, for patients treated with 66 Gy.Conclusion:The use of VMAT technique for radiation therapy of high-risk prostate cancer patients is an efficient and reliable method for achieving superior dose conformity, uniformity and homogeneity to the PTV and minimal doses to the organs at risk. Results from this study provide the basis for the development and implementation of consistent treatment criteria in radiotherapy programs, have the potential to establish an evaluation process to define a consistent, standardised and transparent treatment path for all patients that reduces significant variations in the acceptability of treatment plans and potentially improve patient standard of care.

CyberKnife Boost in Pediatric Ependymoma of the Fourth Ventricle

Background: Ependymoma of the fourth ventricle is a challenging disease. Brain stem tolerance dose usually hinders the delivery of adequate radiation dose to target volumes. Aim: To present the treatment outcome of pediatric ependymoma of the fourth ventricle using combined CyberKnife and volumetric modulated arc therapy (VMAT) and compare it to VMAT plans. Methods: The medical charts of 15 patients were retrospectively reviewed. All patients underwent surgery and received radiotherapy in 2 phases using combined plans of VMAT and CyberKnife boost aiming for a total prescription dose of 59.4 Gy in 33 fractions. These plans were compared to a cone-down two-phase VMAT plans. At least 95% of the target volume was required to be encompassed by the 95% isodose level of prescription dose. Results: It was not feasible to achieve adequate target coverage using VMAT without exceeding the brain stem tolerance doses in all but one case. Brain stem maximum point dose, V59 Gy, V55.8 Gy and mean doses were 60.46 ± 0.3 Gy, 1.62 ± 0.42 cc, 37.49 ± 5.78% and 54.79 ± 0.64 Gy in VMAT plans compared to 59.67 ± 0.21 Gy, 0.55 ± 0.22 cc, 25.49 ± 3.84% and 52.86 ± 0.88 Gy in combined technique plans (p = 0.002, 0.001, 0.001 and 0.001; respectively). The estimated 5-year progression-free and overall survival rates were 53.3% and 63.6%. Performance status and extent of surgery significantly influenced overall survival. None of the patients had serious toxicities. Conclusion: On the contrary to VMAT cone-down plans, it was possible to achieve adequate target coverage without violating brain stem constraints using the combination of VMAT and CyberKnife techniques in pediatric ependymoma of the fourth ventricle. The treatment protocol was well tolerated with no reported serious radiation toxicities.

Proton and carbon ion radiotherapy in skull base chordomas: a prospective study based on a dual particle and a patient-customized treatment strategy.

The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT). We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes. After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients. Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC. • Proton and carbon ion therapy are effective and safe in skull base chordoma.• Prognostic factors are GTV, organs at risk compression, and dose coverage.• Dual particle therapy and customized strategy was adopted.

Clinical outcomes and prognostic factors of stereotactic body radiation therapy combined with gemcitabine plus capecitabine for locally advanced unresectable pancreatic cancer.

This study aimed to evaluate the clinical outcomes, toxicity, and prognostic factors of SBRT combined with gemcitabine plus capecitabine (GEM-CAP) in treating locally advanced pancreatic cancer (LAPC). A total of 56 patients with LAPC treated with SBRT combined with GEM-CAP were reviewed from October 2010 to October 2016. The median total prescription dose at five fractions was 40Gy (30-50Gy). The patients were subjected to two cycles of GEM-CAP before SBRT. GEM-CAP chemotherapy was then offered for four cycles or until disease tolerance or progression. The primary endpoints included overall survival (OS) and progression-free survival (PFS). The median OS and PFS from the date of diagnosis was 19 (95% CI 14.6-23.4) and 12months (95% CI 8.34-15.66), respectively. The 1-year and 2-year survival rates were 82.1% and 35.7%, whereas the 1-year and 2-year PFS rates were 48.2% and 14.3%, respectively. The median carbohydrate antigen 19-9-determined PFS time was 11months (95% CI 5.77-16.24). Multivariate analysis demonstrated that tumor diameter, lymph node metastasis, pre-treatment CA19-9 level, and post-treatment CA19-9 decline were independent prognostic factors (p < 0.05). Acute toxicity was minimal, with two cases (3.6%) experiencing grade 3 duodenal obstruction. No adverse events greater than grade 3 occurred. In late toxicity, three patients (5.4%) developed grade 3 gastrointestinal toxicity and two (3.6%) suffered from perforation caused by grade 4 radiation enteritis and intestinal fistula. The combination of Cyberknife SBRT and GEM-CAP achieved excellent efficacy with acceptable toxicity for LAPC.

EP1.18-14 Algorithm for Deciding Radiotherapy Technique in Stage III Non-Small Cell Lung Cancer

Concurrent chemoradiotherapy has shown superior survival outcomes in inoperable, Stage III non-small cell lung cancer (NSCLC) with good performance status. Usage of 3-dimensional conformal radiotherapy (3D-CRT) technique is commonest with intensity modulated radiotherapy (IMRT) gaining popularity owing to its ability to spare normal tissues. In our study we analysed the tumour and nodal characteristics of patients to predict which technique maybe beneficial by generating optimised plans of both 3D-CRT and volumetric modulated arc radiotherapy (VMAT), a type of IMRT. A total of 27 Stage III NSCLC patients underwent PET-CT (in the treatment position) co-registered treatment planning using either 3D-CRT or VMAT. The total prescription dose was 60 Gy in 30 fractions over 6 weeks with concurrent cisplatin based chemotherapy. Retrospectively alternate treatment plans were generated to obtain two sets of plans (3D-CRT and VMAT) of each patient for dosimetric comparison. The tumour and nodal characteristics and treatment technique were analysed to identify predictive factors limiting total dose delivery. The angle of contact of the PTV with the circumference of the vertebral body was calculated for patients where the tumour or nodal mass was in contact with the vertebral body (Figure 1). Of the 27 patients enrolled, 6 patients could not be planned to the complete dose of 60 Gy in a single phase by 3D-CRT. Dose limiting factors were high spinal cord doses due to vertebral body erosion (2 out of 6) and bilateral bulky mediastinal lymphadenopathy (4 out of 6). Alternate VMAT plans for these patients could achieve the dose constraints in all but the two patients with vertebral body erosion. Differences in the normal tissue doses of bilateral normal lungs, esophagus, heart and spinal cord were compared between both techniques to ascertain statistical significance. The spatial location of the tumour and nodal burden rather than the volume limited the maximum dose delivered. For tumours with vertebral body contact of more than 90 degrees, VMAT should be used. With gross vertebral body erosion, even VMAT falls short if the PTV includes the spinal cord. In view of high patient volume and limited resources, VMAT is not an economical option for all patients. A simple clinical algorithm is outlined (Figure 1) which will help select patients who will best benefit from VMAT.

Clinical Outcomes of Volumetric Modulated Arc Therapy Following Intracavitary/Interstitial Brachytherapy in Cervical Cancer: A Single Institution Retrospective Experience.

Purpose: To evaluate treatment outcomes and toxicity in patients with cervical cancer (CC) treated with volumetric modulated arc therapy (VMAT), followed by three-dimensional high-dose-rate intracavity combined with interstitial brachytherapy (IC/IS BT) compared with intensity-modulated radiation therapy (IMRT) treatment.Materials and Methods: A total of 398 patients with stage IA–IVB CC treated with definitive radiotherapy with or without chemotherapy were retrospectively analyzed (331 VMAT and 67 IMRT). A total prescription dose of 45–50 Gy was delivered to pelvic field with VMAT/IMRT in 25/28 fractions, with five fractions per week. Every patient further received IC/IS BT for four to six 6.0-Gy fractions. Local control (LC), disease-free survival (DFS), overall survival (OS), and distant metastasis-free survival (DMFS) rates were calculated. Acute hematotoxicity and late toxicity were recorded.Results: The median follow-up period was 25.47 (range, 0.93–58.93) months for the VMAT and 35.07 (4.8–90.37) months for IMRT. The 3-year OS, DFS, LC, and DMFS rate were 80.5, 65.4, 88.7, and 78.1% in VMAT group, and 76.2, 76.4, 83.1, and 86.1% in the IMRT group, respectively. No significant differences were found between VMAT and IMRT groups for OS, DFS, LC, and DMFS rate. However, patients in the VMAT group had lower incidence of chronic enterocolitis complication (26.6 vs. 38.8%, p = 0.004). In addition, a total of 3 (0.9%) patients developed grade 3 chronic cystitis, and 7 (2.1%) patients developed grade 3 or greater chronic enterocolitis in VMAT group.Conclusion: VMAT combined with IC/IS BT can result in satisfactory curative outcomes and low incidences of late radiation enterocolitis and cystitis in CC treatment.

Analysis of prescription pattern of the fentanyl citrate sublingual tablets according to liver or kidney function abnormality of cancer patients.

119 Background: Many advanced cancer patients eventually develop liver dysfunction or renal insufficiency during the course of their disease. However, there is limited evidence for optimally safe drug for pain control in these situation. To estimate the safety of fentanyl citrate sublingual tablets (FSTs) in kidney or hepatic dysfunction, we analyzed whether the total prescription dose or prescription period of FSTs is associated with their liver function test (LFT) or estimated glomerular filtration rate (eGFR). Methods: We retrospectively enrolled consecutive cancer patients who prescribed FSTs at least once from July 2015 to June 2017. Results: Total 611 patients were identified. Median age was 63.6 (18-89) years. Total dose of prescribed FSTs is vary widely among pts; mean 23330 ± 42111 mcg, median 8400 mcg. About kidney function, eGFR could be calculated in 523 patients (85.6%). In 80 pts (15.3%), eGFR is below 60 mL/min/1.73 m2. The total dose of prescribed FSTs have no significant correlation with grade of CKD. The duration of prescription of FSTs was shorter in patients with eGFR &lt; 60 in compared to those with eGFR ≥60; median 42 days versus 66 days (p &lt; 0.001). On the other hand, 535 pts (87.6%) have result of LFT prior to be prescribed FSTs. Significant LFT abnormality is found in 158 pts (29.5%). The total dose of prescribed FSTs have weak negative correlation with LFT level (p &lt; 0.001). The total dose of FSTs is significantly lower in pts with G3/4 LFT abnormality in compared to those with normal or G1/2 LFT abnormality. The duration of prescription of FSTs was significantly shorter in patients with G3/4 liver dysfunction in compared to those with normal or G1/2 liver dysfunction; median 30 days versus 83 days (p = 0.002). In the multivariate analysis, both G3/4 LFT and decreased eGFR are significant factors for shorter duration of prescription by the Cox proportional hazard model. Conclusions: When cancer patients have renal insufficiency or significant liver dysfunction, FSTs were used in a smaller dose for a shorter period of time. We need prospective study on the efficacy and safety of FSTs in cancer patients with liver dysfunction or renal insufficiency.

The effect of breast volume on toxicity using hypofractionated regimens for early stage breast cancer for patients

PurposeHypofractionated radiation therapy (HFRT) remains underused, despite multiple randomized trials showing the equivalence of HFRT to conventional fractionated radiation therapy (CFRT). We sought to retrospectively review the relationship between breast volume and toxicity for HFRT versus CFRT. Methods and materialsData from 114 patients who received a diagnosis of early stage breast cancer and were treated with lumpectomy and whole breast radiation alone were reviewed. Breast cancer laterality, stage, grade, estrogen/progesterone receptor and human epidermal growth factor receptor 2 status, and systemic therapy use were recorded. Length of follow-up was calculated using the last day of radiation treatment and the date of the most recent follow-up. ResultsThe median follow-up was 42 months. A total of 83 patients were treated with HFRT and 31 with CFRT. Rates of grade ≥2 skin toxicity were significantly higher in patients undergoing CFRT compared with HFRT (76% vs 28%; P < .0001). In a subset of patients with breast volume ≥1000 cm3, grade ≥2 skin toxicity trended higher for CFRT patients (73% vs 38%; P = .057). For posterior separation >25 cm, the percentage of patients with grade 2 skin toxicity was 43% for HFRT versus 57% for CFRT (P = .67). The volume of breast tissue receiving >105% of the total prescription dose, including boost, was not significantly different for HFRT versus CFRT (P = .70). ConclusionsUse of HFRT resulted in lower acute skin toxicity rates compared with CFRT. Large breast size (volume ≥1000 cm3) was associated with lower acute grade 2 toxicity with the use of HFRT despite achieving similar dosimetry compared with CFRT.