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3.
Radiother Oncol ; 182: 109571, 2023 05.
Article in English | MEDLINE | ID: mdl-36822361

ABSTRACT

BACKGROUND AND PURPOSE: Radiation dose prescriptions are foundational for optimizing treatment efficacy and limiting treatment-related toxicity. We sought to assess the lack of standardization of SBRT dose prescriptions across institutions. MATERIALS & METHODS: Dosimetric data from 1298 patients from 9 academic institutions treated with IMRT and VMAT were collected. Dose parameters D100, D98, D95, D50, and D2 were used to assess dosimetric variability. RESULTS: Disease sites included lung (48.3 %) followed by liver (29.7 %), prostate (7.5 %), spine (6.8 %), brain (4.1 %), and pancreas (2.5 %). The PTV volume in lung varied widely with bimodality into two main groups (22.0-28.7 cm3) and (48.0-67.1 cm3). A hot spot ranging from 120-150 % was noted in nearly half of the patients, with significant variation across institutions. A D50 ≥ 110 % was found in nearly half of the institutions. There was significant dosimetric variation across institutions. CONCLUSIONS: The SBRT prescriptions in the literature or in treatment guidelines currently lack nuance and hence there is significant variation in dose prescriptions across academic institutions. These findings add greater importance to the identification of dose parameters associated with improved clinical outcome comparisons as we move towards more hypofractionated treatments. There is a need for standardized reporting to help institutions in adapting treatment protocols based on the outcome of clinical trials. Dosimetric parameters are subsequently needed for uniformity and thereby standardizing planning guidelines to maximize efficacy, mitigate toxicity, and reduce treatment disparities are urgently needed.


Subject(s)
Radiosurgery , Radiotherapy, Intensity-Modulated , Male , Humans , Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Dosage , Prescriptions
4.
Mol Pharm ; 19(8): 2776-2794, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35834797

ABSTRACT

For many locally advanced tumors, the chemotherapy-radiotherapy (CT-RT) combination ("chemoradiation") is currently the standard of care. Intratumoral (IT) CT-based chemoradiation has the potential to overcome the limitations of conventional systemic CT-RT (side effects). For maximizing the benefits of IT CT-RT, our laboratory has previously developed a radiation-controlled drug release formulation, in which anticancer drug paclitaxel (PTX) and radioluminescent CaWO4 (CWO) nanoparticles (NPs) are co-encapsulated with poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) block copolymers ("PEG-PLA/CWO/PTX NPs"). These PEG-PLA/CWO/PTX NPs enable radiation-controlled release of PTX and are capable of producing sustained therapeutic effects lasting for at least one month following a single IT injection. The present article focuses on discussing our recent finding about the effect of the stereochemical structure of PTX on the efficacy of this PEG-PLA/CWO/PTX NP formulation. Stereochemical differences in two different PTX compounds ("PTX-S" from Samyang Biopharmaceuticals and "PTX-B" from Biotang) were characterized by 2D heteronuclear/homonuclear NMR, Raman spectroscopy, and circular dichroism measurements. The difference in PTX stereochemistry was found to significantly influence their water solubility (WS); PTX-S (WS ≈ 4.69 µg/mL) is about 19 times more water soluble than PTX-B (WS ≈ 0.25 µg/mL). The two PTX compounds showed similar cancer cell-killing performances in vitro when used as free drugs. However, the subtle stereochemical difference significantly influenced their X-ray-triggered release kinetics from the PEG-PLA/CWO/PTX NPs; the more water-soluble PTX-S was released faster than the less water-soluble PTX-B. This difference was manifested in the IT pharmacokinetics and eventually in the survival percentages of test animals (mice) treated with PEG-PLA/CWO/PTX NPs + X-rays in an in vivo human tumor xenograft study; at short times (<1 month), concurrent PEG-PLA/CWO/PTX-S NPs produced a greater tumor-suppression effect, whereas PEG-PLA/CWO/PTX-B NPs had a longer-lasting radio-sensitizing effect. This study demonstrates the importance of the stereochemistry of a drug in a therapy based on a controlled release formulation.


Subject(s)
Nanoparticles , Neoplasms , Animals , Cell Line, Tumor , Drug Carriers/chemistry , Humans , Mice , Nanoparticles/chemistry , Neoplasms/drug therapy , Paclitaxel/chemistry , Polyethylene Glycols/chemistry , Water , X-Rays
6.
Dysphagia ; 37(4): 848-855, 2022 08.
Article in English | MEDLINE | ID: mdl-34283289

ABSTRACT

An isotropic expanded Planning Target Volume (PTV) neglects patient's off-axis rotation. This study designs a rotational PTV that is used instead of the standard 3-mm Clinical Target Volume (CTV) expanded PTV in oropharyngeal cancers with the goal to reduce pharyngeal constrictor muscle (PCM) mean dose. 10 patients were retrospectively evaluated. For off-axis rotation, the image was rotated around the longitudinal axis (cervical spinal canal) ± 5 degrees. These new CTVs were combined to form the rotational PTV. The standard and rotational treatment plans were designed with the goal to keep the superior and middle PCM-CTV70 mean dose to less than 50 Gy. There were a 355 cGy reduction in the superior PCM mean dose (form 5332 to 4977 cGy) and a 506 cGy reduction in middle PCM mean dose (from 4185 to 3679 cGy). 60% of patients may have at least a 20% reduction in dysphagia probability based on a Normal Tissue Complication Probability (NTCP) formula. The superior and middle PCM mean dose were reduced to less than 50 Gy in 40 and 20% of cases. There was an association between superior PCM mean dose and overlap volume of PTV70 and superior PCM in both standard (r = 0.92, p = 0.001) and rotational (r = 0.84, p = 0.002) plans. This association was present for middle PCM and PTV70 (r = 0.52, p = 0.02 and r = 0.62, p = 0.006). Rotational PTV can lower the mean dose to superior and middle PCMs, ultimately leading to lower dysphagia rates.


Subject(s)
Deglutition Disorders , Oropharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Retrospective Studies
7.
Orv Hetil ; 162(43): 1740-1743, 2021 10 24.
Article in Hungarian | MEDLINE | ID: mdl-34689133

ABSTRACT

Összefoglaló. Bevezetés: A sinus pilonidalis nehezen kezelheto, sok szövodménnyel és recidívával járó betegség. A legtöbb mutéti eljárás többnapos kórházi kezelést, munkából vagy iskolából való hiányzást követel. Célkituzés: Munkánk célja, hogy a PEPSiT- (pediatric endoscopic pilonidal sinus treatment) mutétek eredményességét vizsgálja. Módszer: Intézetünkben 2019-2020-ban PEPSiT-mutéten átesett, 18 év alatti betegeket válogattunk be a vizsgálatba. Kizártuk a cisztoszkóppal operált és kontrollra nem jelentkezo betegeket. A szövodmények, recidívák számát, a kórházi tartózkodás hosszát, a sebgyógyulás és a hétköznapi aktivitáshoz való visszatérés idejét vizsgáltuk. Eredmények: Betegeink többsége fiú (24 fiú, 4 lány), átlagéletkoruk 15,6 év volt. 28 betegen 31 PEPSiT-beavatkozást végeztünk (3 re-PEPSiT), 6 recidíva, 1 sebgennyedés alakult ki. A betegek egy része egynapos ellátás keretében, míg a többség egy éjszaka bentfekvés után tért haza (1,74 nap ápolási ido). A hétköznapi aktivitáshoz 1,37 nap után tértek vissza, a gyógyulási ido 5,9 hét volt átlagosan. Megbeszélés: A PEPSiT-beavatkozás minimálisan invazív lehetoség, igen rövid kórházi tartózkodással. A betegek hamar térnek vissza a szokott aktivitásukhoz, a korábbi sipolyon kívül újabb mutéti seb nem alakul ki. A recidívaarány hasonló az egyéb technikákéhoz. Következtetés: A PEPSiT-beavatkozás jól alkalmazható, a recidívaarány csökkentése fontos. Orv Hetil. 2021; 162(43): 1740-1743. INTRODUCTION: The treatment of pilonidal disease is often challenging, due to frequent recurrences and adverse events. Most operative treatments require a lengthy hospital stay, and absence from school or work. OBJECTIVE: We aimed towards assessing the effectivity of PEPSiT (pediatric endoscopic pilonidal sinus treatment). METHOD: In this study, we included patients subjected to PEPSiT from 2019 to 2020 between ages 0-18 years. Patients operated via cystoscope and patients who did not attend follow-up examinations were excluded. Adverse events, recurrences, length of hospital stay, wound healing time and return to everyday activity were assessed. RESULTS: The majority of our patients were male (24 male, 4 female), the mean age was 15.6 years. 31 PEPSiT operations were recorded on 28 patients (3 were redo surgeries). 6 recurrences and 1 wound suppuration were documented. Some patients were treated within the confines of one-day surgery, while most of them stayed one night (mean length of stay was 1.74 days). Return to everyday activity was an average 1.37 days, and mean wound healing time was 5.9 weeks. DISCUSSION: PEPSiT is a minimally invasive operative approach with a very short hospital stay. Patients return to everyday activity faster. New operative scarring does not happen apart from the preexisting fistula opening. Recurrence rate is similar to that of other treatment techniques. CONCLUSION: PEPSiT technique is applicable, however, reduction of the recurrence rate is important. Orv Hetil. 2021; 162(43): 1740-1743.


Subject(s)
Pilonidal Sinus , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Length of Stay , Male , Neoplasm Recurrence, Local , Pilonidal Sinus/surgery , Retrospective Studies
8.
Radiother Oncol ; 156: 231-238, 2021 03.
Article in English | MEDLINE | ID: mdl-33096168

ABSTRACT

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) can be a potential fatal toxicity of stereotactic body radiation therapy (SBRT) for medically inoperable non-small cell lung cancer (NSCLC). This study aimed to examine the risk factors that predict RP and explore dosimetric tolerance for safe practice in a large institutional series of NSCLC patients. MATERIALS AND METHODS: Patients with early-stage and locally recurrent NSCLC who received lung SBRT between 2002 and 2015 formed the study population. The primary endpoint was grade 2 or above radiation pneumonitis (RP2). Lungs were re-contoured consistently by one radiation oncologist according to the RTOG atlas for organs at risk. Dosimetric factors were computed consistently with exclusion of gross tumor volume of either ipsilateral, contralateral, or total lungs. RESULTS: A total of 339 patients were eligible. With a median follow-up of 47 months, RP2 was recorded in 10% patients. History of respiratory comorbidity, previous thoracic radiation, right lung location, mean lung doses of total or ipsilateral lung, and total lung volume receiving 20 Gy were all significantly associated with the risk of RP2. The dosimetric parameters of contralateral lung, including mean dose and volume receiving more than 5, 10, and 20 Gy, were not significantly associated with RP2 (ps > 0.05). A model of combining significant clinical and dosimetric factors had a predictive accuracy AUC of 0.76. According to this model, RP2 can be limited to <10% should the patient have no previous lung radiation and the mean dose of total and ipsilateral lungs be kept less than 6 Gy and 20 Gy, respectively. CONCLUSION: Dosimetric factors of total or ipsilateral lung together with important clinical factors were significant risk factors for symptomatic radiation pneumonitis after SBRT. Constraining mean lung dose can limit clinically significant lung toxicity.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiation Pneumonitis , Radiosurgery , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Neoplasm Recurrence, Local , Radiation Pneumonitis/epidemiology , Radiation Pneumonitis/etiology , Radiosurgery/adverse effects , Risk Factors
9.
Clin Lung Cancer ; 22(3): e342-e359, 2021 05.
Article in English | MEDLINE | ID: mdl-32736936

ABSTRACT

INTRODUCTION: The impact of lung parenchymal-only failure on patient survival after stereotactic ablative body radiotherapy (SABR) for early-stage non-small-cell lung cancer (NSCLC) remains unclear. PATIENTS AND METHODS: The study population included 481 patients with early-stage NSCLC who were treated with 3- to 5-fraction SABR between 2000 and 2016. The primary study objective was to assess the impact of out-of-field lung parenchymal-only failure (OLPF) on overall survival (OS). RESULTS: At a median follow-up of 5.9 years, the median OS was 2.7 years for all patients. Patients with OLPF did not have a significantly different OS compared to patients without failure (P = .0952, median OS 4.1 years with failure vs. 2.6 years never failure). Analysis in a 1:1 propensity score-matched cohort for Karnofsky performance status, comorbidity score, and smoking status showed no differences in OS between patients without failure and those with OLPF (P = .8). In subgroup analyses exploring the impact of time of failure on OS, patients with OLPF 6 months or more after diagnosis did not have significantly different OS compared to those without failure, when accounting for immortal time bias (P = .3, median OS 4.3 years vs. 3.5 years never failure). Only 7 patients in our data set experienced failure within 6 months of treatment, of which only 4 were confirmed to be true failures; therefore, limited data are available in our cohort on the impact of OLPF for ≤ 6 months on OS. CONCLUSION: OLPF after SABR for early-stage NSCLC does not appear to adversely affect OS, especially if occurring at least 6 months after SABR. More studies are needed to understand if OLPF within 6 months of SABR is associated with adverse OS. These data are useful when discussing prognosis of lung parenchymal failures after initial SABR.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Parenchymal Tissue/pathology , Radiosurgery/methods , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Survival Rate , Treatment Outcome
10.
J Appl Clin Med Phys ; 21(11): 172-178, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33078521

ABSTRACT

BACKGROUND: Planning target volume (PTV) has been used to account for variations in tissue, patient and beam position. In oropharyngeal cancers, an isotropic expanded PTV has been used. AIM: The aim of this study was to design a new margin formula that would cover the space occupied by an oropharyngeal clinical target volume (CTV) with ±5-degree rotation around the spine in order to reduce the pharyngeal constrictors overlap with PTV compared to an isotropic expanded PTV. METHODS: We retrospectively evaluated 20 volumetric-modulated arc therapy (VMAT) plans. In order to perform an off-axis rotation, a hypothetical point was placed through the center of the cervical spinal canal and the image was then rotated around the longitudinal axis ±5 degrees. This created a new set of CTVs that were combined to form the new rotational PTV. The overlap between the pharyngeal constrictor muscles (PCMs) and both PTVs was then evaluated. RESULTS: The new rotational PTV causes reduction in the superior PCM overlap in the base of tongue (BOT) lesions compared to tonsillar lesion, 57.8% vs 25.8%, P = 0.01, as well as middle PCM overlap, 73% vs 49%, P = 0.04. Average percent change for PTV volume and overlap with the superior, middle, and inferior PCMs are as followed: -19%, -37%, -59.4%, and -45.2. The smallest isotropic expansion that covers the new rotational PTV was between 3 and 5mm with the average tumor center shift of 0.49 cm. CONCLUSION: This new rotational PTV causes significant reduction of the overlap volume between PCMs and PTVs in order to spare the PCMs compared to isotropic expanded PTV.


Subject(s)
Oropharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Muscles , Oropharyngeal Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Retrospective Studies
11.
Med Dosim ; 45(3): 293-297, 2020.
Article in English | MEDLINE | ID: mdl-32249105

ABSTRACT

PURPOSE: We demonstrate proof of principle that normal tissue doses can be greatly reduced in lung stereotactic body radiation therapy (SBRT) for mobile tumors, if the delivered dose is split between opposite respiratory states. METHODS: Patients that underwent 5 fraction lung SBRT at our institution and had deep inspiration breath hold (DIBH) and free breathing 4D computed tomography scans were included. Volumetric modulated arc therapy plans were generated on both respiratory phases and a third composite plan was generated delivering half the dose using the DIBH plan and the other half using the expiratory phase plan for each fraction. Computed tomography scans for the composite plan were fused based on ribs adjacent to the tumor to evaluate the dose volume histogram of critical structures. RESULTS: Four patients with 4 total tumors had requisite planning scans available. Tumor size was between 0.7 to 2.9 cm and tumor movement 1.4 to 2.9 cm. Median reduction in the chest wall (CW) V30Gy for the composite plan was 74.6% (range 33.7 to 100%), 76.9% (range 32.9 to 100%), and 89.3% (range 69.5 to 100%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Median reduction in CW maximum dose for the composite plan was 23.3% (range 0.27% to 46.4%), 23.5% (range 3.2 to 48.2%), and 23.4% (range 0.27% to 48.4%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Greater reduction in CW maximum dose was observed when patients had no overlap in planning target volumes between DIBH and expiration phases (median reduction 43.9% for no overlap vs 2.7% with overlap). Between all plans, lung V20Gy absolute differences were within 1.3%. For 2 of 4 patients, the composite plan met constraints for 3 fraction SBRT, while standard plans did not. CONCLUSIONS: We conclude that composite DIBH-expiration SBRT planning has the potential to improve organ at risk sparing.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Breath Holding , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Exhalation , Four-Dimensional Computed Tomography , Humans , Inhalation , Lung Neoplasms/diagnostic imaging , Organs at Risk , Radiation Dosage , Radiosurgery , Retrospective Studies
12.
Article in English | MEDLINE | ID: mdl-33969361

ABSTRACT

This objective of this paper is to develop a dual quaternion based method for estimating target volumes in radiation therapy for head and neck cancer. Inaccuracies in radiation targeting are responsible for incidental exposure of healthy adjacent tissues, causing significant morbidity and mortality. This paper focuses on inaccuracies incurred when a tumor is displaced during treatment. To address this problem, the clinical target must be expanded to cover the region through which the tumor might move. The resulting expanded target is known as the Planning Target Volume (PTV). In the current practice, the rotational components of displacements are neglected, producing planning target volumes that either miss the true target motion or are larger than needed to cover the target path. By using the dual quaternion based kinematic formulation, this paper represents and captures both translational and rotational inaccuracies. It then presents a framework for calculating the PTV swept out by the target as it shifts within its range of translations and rotations.

13.
J Control Release ; 303: 237-252, 2019 06 10.
Article in English | MEDLINE | ID: mdl-31026550

ABSTRACT

The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO4 (CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30-40 fractions of 2-3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle ("PEG-PLA/CWO/PTX") formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1 month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1 month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO4, or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Calcium Compounds/administration & dosage , Drug Delivery Systems , Luminescent Agents/administration & dosage , Nanoparticles/administration & dosage , Paclitaxel/administration & dosage , Polyethylene Glycols/administration & dosage , Tungsten Compounds/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/chemistry , Calcium Compounds/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Chemoradiotherapy , Drug Liberation , Female , Humans , Luminescent Agents/chemistry , Mice , Nanoparticles/chemistry , Neoplasms/therapy , Paclitaxel/chemistry , Polyethylene Glycols/chemistry , Tungsten Compounds/chemistry
14.
Clin Lung Cancer ; 20(3): 186-193.e3, 2019 05.
Article in English | MEDLINE | ID: mdl-30711394

ABSTRACT

INTRODUCTION/BACKGROUND: Many patients with early stage non-small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. MATERIALS AND METHODS: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. RESULTS: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P < .001 and hazard ratio [HR], 1.02 per mL; P < .05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) - (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. CONCLUSION: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Lung Neoplasms/radiotherapy , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/radiotherapy , Disease Progression , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prognosis , Radiotherapy Dosage , Retrospective Studies , Risk Factors , Treatment Failure , Tumor Burden
15.
Med Dosim ; 44(3): 291-299, 2019.
Article in English | MEDLINE | ID: mdl-30097226

ABSTRACT

The purpose of this study is to evaluate the dosimetric differences to the lung internal target volume (ITV) in stereotactic body radiation therapy (SBRT) when calculated on the free breathing (FB) scan in comparison to calculations on the average intensity projection (AIP) scan as well as the sum of dose calculated on each of the treated respiratory phases. The clinical treatment plan data for 16 SBRT lung patients were retrospectively chosen for this study, 5 of which were 30% to 70% respiratory phase gated. All patients had ITV contours and fixed monitor units from the treatment approved plan copied over to each scan on which calculations were to be made. The results of this study yielded 6 out of 16 patients with greater than or equal to 2% difference in ITV maximum dose (D0) and 2 of 16 patients with greater than or equal to 2% difference in ITV minimum dose (D100). The range of ITV dose differences for these 8 patients was 2% to 4.7% with no patients exceeding a 5% difference in D0 or D100. None of the patients had greater than or equal to 2% difference in ITV mean dose (Dmean). Sixty-three percent of patients with greater than 2% ITV dose difference in any of the categories reviewed were those patients with greater than 1 cm gross tumor motion. This study concluded that in order to reduce uncertainty in dose to the ITV, tumor motion should be assessed at simulation and limited to below 1 cm in any direction if possible.


Subject(s)
Four-Dimensional Computed Tomography/methods , Lung Neoplasms/radiotherapy , Radiosurgery/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Datasets as Topic , Humans , Lung Neoplasms/diagnostic imaging , Respiration , Retrospective Studies
16.
J Thorac Oncol ; 13(10): 1549-1559, 2018 10.
Article in English | MEDLINE | ID: mdl-29959060

ABSTRACT

INTRODUCTION: It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC. METHODS: The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed. RESULTS: At 6.7 years median follow-up, 3-year in-field control, involved lobe control, overall survival, and progression-free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with α/ß = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005-1.022, p = 0.0012). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively). CONCLUSIONS: In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Radiosurgery/methods , Radiotherapy Dosage/standards , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Treatment Outcome , Tumor Burden
17.
Pract Radiat Oncol ; 7(2): e145-e155, 2017.
Article in English | MEDLINE | ID: mdl-28274405

ABSTRACT

PURPOSE: The purpose of this study was to evaluate dose prescription and recording compliance to international standard (International Commission on Radiation Units & Measurements [ICRU]-83) in patients treated with intensity modulated radiation therapy (IMRT) among academic institutions. METHODS AND MATERIALS: Ten institutions participated in this study to collect IMRT data to evaluate compliance to ICRU-83. Under institutional review board clearance, data from 5094 patients-including treatment site, technique, planner, physician, prescribed dose, target volume, monitor units, planning system, and dose calculation algorithm-were collected anonymously. The dose-volume histogram of each patient, as well as dose points, doses delivered to 100% (D100), 98% (D98), 95% (D95), 50% (D50), and 2% (D2), of sites was collected and sent to a central location for analysis. Homogeneity index (HI) as a measure of the steepness of target and is a measure of the shape of the dose-volume histogram was calculated for every patient and analyzed. RESULTS: In general, ICRU recommendations for naming the target, reporting dose prescription, and achieving desired levels of dose to target were relatively poor. The nomenclature for the target in the dose prescription had large variations, having every permutation of name and number contrary to ICRU recommendations. There was statistically significant variability in D95, D50, and HI among institutions, tumor site, and technique with P values < .01. Nearly 95% of patients had D50 higher than 100% (103.5 ± 6.9) of prescribed dose and varied among institutions. On the other hand, D95 was close to 100% (97.1 ± 9.4) of prescribed dose. Liver and lung sites had a higher D50 compared with other sites. Pelvic sites had a lower variability indicated by HI (0.13 ± 1.21). Variability in D50 is 101.2 ± 8.5, 103.4 ± 6.8, 103.4 ± 8.2, and 109.5 ± 11.5 for IMRT, tomotherapy, volume modulated arc therapy, and stereotactic body radiation therapy with IMRT, respectively. CONCLUSIONS: Nearly 95% of patient treatments deviated from the ICRU-83 recommended D50 prescription dose delivery. This variability is significant (P < .01) in terms of treatment site, technique, and institution. To reduce dosimetric and associated radiation outcome variability, dose prescription in every clinical trial should be unified with international guidelines.


Subject(s)
Guideline Adherence/statistics & numerical data , Practice Guidelines as Topic , Radiotherapy, Intensity-Modulated/standards , Analysis of Variance , Humans , Male , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Retrospective Studies , Treatment Outcome
18.
JAMA Otolaryngol Head Neck Surg ; 142(10): 972-979, 2016 10 01.
Article in English | MEDLINE | ID: mdl-27467967

ABSTRACT

Importance: The accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator has been assessed in multiple surgical subspecialties; however, there have been no publications doing the same in the head and neck surgery literature. Objective: To evaluate the accuracy of the calculator's predictions in a single institution's total laryngectomy (TL) population. Design, Setting, and Participants: Total laryngectomies performed between 2013 and 2014 at a tertiary referral academic center were evaluated using the risk calculator. Predicted 30-day outcomes were compared with observed outcomes for return to operating room, surgical site infection, postoperative pneumonia, length of stay, and venous thromboembolism. Main Outcomes and Measures: Comparison of the NSQIP risk calculator's predicted postoperative complication rates and length of stay to what occurred in this patient cohort using percent error, Brier scores, area under the receiver operating characteristic curve, and Pearson correlation analysis. Results: Of 49 patients undergoing TL, the mean (SD) age at operation was 59 (9.3) years, with 67% male. The risk calculator had limited efficacy predicting perioperative complications in this group of patients undergoing TL with or without free tissue reconstruction or preoperative chemoradiation or radiation therapy with a few exceptions. The calculator overestimated the occurrence of pneumonia by 165%, but underestimated surgical site infection by 7%, return to operating room by 24%, and length of stay by 13%. The calculator had good sensitivity and specificity of predicting surgical site infection for patients undergoing TL with free flap reconstruction (area under the curve, 0.83). For all other subgroups, however, the calculator had poor sensitivity and specificity for predicting complications. Conclusions and Relevance: The risk calculator has limited utility for predicting perioperative complications in patients undergoing TL. This is likely due to the complexity of the treatment of patients with head and neck cancer and factors not taken into account when calculating a patient's risk.


Subject(s)
Laryngectomy , Postoperative Complications , Female , Forecasting , Humans , Male , Middle Aged , Postoperative Complications/prevention & control , Quality Improvement , Risk Assessment/methods
19.
Pract Radiat Oncol ; 5(6): e673-8, 2015.
Article in English | MEDLINE | ID: mdl-26419442

ABSTRACT

BACKGROUND: In 2014, the Association of Directors of Radiation Oncology Programs (ADROP) conducted an in-depth survey of program directors along several axes. We report the results of this survey and compare the major findings with those of the 2007 ADROP survey. METHODS AND MATERIALS: The survey was written and approved by ADROP leadership in 2012, announced online through broadcasts throughout 2013 and early 2014, and closed in mid-2014. The results based on question groups related to (1) hours spent in activities, (2) budget and nonprogram resources, (3) physics/biology didactics, (4) mock exams/didactics/research, (5) electives, (6) students, and (7) resources/challenges were tabulated. Descriptive comparisons with the 2007 survey were performed. RESULTS: There was 26% participation (23/88 programs). Major areas of time commitment were faculty and site organization, maintenance, and corrections (70 hours/year) and didactics/conferences and rounds (200 hours/year). The median program director protected time was 23% (range 0%-50%). All responding programs (100%) had biology and physics courses and assigned directors, but only approximately 20% of respondents had a threshold grade in these courses for graduation. Major resources desired were templates of goals/objectives by disease site, competency evaluations by level, journal club repository, and software for contouring, oral examination preparation, grant writing, publication writing, oral presentation, and effective teaching. Major activity challenges were Accreditation Council for Graduate Medical Education external review and time commitment. CONCLUSIONS: Overall, the 2014 results are similar to those of the 2007 survey. The average time commitment remains considerably higher than the 10% minimum required in the current ACGME program requirements. The survey results may guide ADROP membership in centralizing some of the identified resources needed.


Subject(s)
Education, Medical, Graduate/standards , Internship and Residency/standards , Radiation Oncology/education , Radiation Oncology/standards , Data Collection , Education, Medical, Graduate/organization & administration , Humans , Internship and Residency/organization & administration , Program Evaluation , Surveys and Questionnaires , Time Factors , Workload
20.
Can Fam Physician ; 61(5): 455, 2015 May.
Article in English | MEDLINE | ID: mdl-25971763
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