Evaluation of treatment planning system accuracy in estimating the stopping-power ratio of immobilization devices for proton therapy.

PURPOSE: To assess treatment planning system (TPS) accuracy in estimating the stopping-power ratio (SPR) of immobilization devices commonly used in proton therapy and to evaluate the dosimetric effect of SPR estimation error for a set of clinical treatment plans. METHODS: Computed tomography scans of selected clinical immobilization devices were acquired. Then, the water-equivalent thickness (WET) and SPR values of these devices based on the scans were estimated in a commercial TPS. The reference SPR of each device was measured using a multilayer ion chamber (MLIC), and the differences between measured and TPS-estimated SPRs were calculated. These findings were utilized to calculate corrected dose distributions of 15 clinical proton plans for three treatment sites: extremity, abdomen, and head-and-neck. The original and corrected dose distributions were compared using a set of target and organs-at-risk (OARs) dose-volume histogram (DVH) parameters. RESULTS: On average, the TPS-estimated SPR was 19.5% lower (range, -35.1% to 0.2%) than the MLIC-measured SPR. Due to the relatively low density of most immobilization devices used, the WET error was typically <1 mm, but up to 2.2 mm in certain devices. Overriding the SPR of the immobilization devices to the measured values did not result in significant changes in the DVH metrics of targets and most OARs. However, some critical OARs showed noticeable changes of up to 6.7% in maximum dose. CONCLUSIONS: The TPS tends to underestimate the SPR of selected proton immobilization devices by an average of about 20%, but this does not induce major WET errors because of the low density of the devices. The dosimetric effect of this SPR error was negligible for most treatment sites, although the maximum dose of a few OARs exhibited noticeable variations.

Is a weekly qualitative picket fence test sufficient? A proposed alternate EPID-based weekly MLC QA program.

PURPOSE: Well-designed routine multileaf collimator (MLC) quality assurance (QA) is important to assure external-beam radiation treatment delivery accuracy. This study evaluates the clinical necessity of a comprehensive weekly (C-Weekly) MLC QA program compared to the American Association of Physics in Medicinerecommended weekly picket fence test (PF-Weekly), based on our seven-year experience with weekly MLC QA. METHODS: The C-Weekly MLC QA program used in this study includes 5 tests to analyze: (1) absolute MLC leaf position; (2) interdigitation MLC leaf position; (3) picket fence MLC leaf positions at static gantry angle; (4) minimum leaf-gap setting; and (5) volumetric-modulated arc therapy delivery. A total of 20,226 QA images from 16,855 tests (3,371 tests × 5) for 11 linacs at 5 photon clinical sites from May 2014 to June 2021 were analyzed. Failure mode and effects analysis was performed with 5 failure modes related to the 5 tests. For each failure mode, a risk probability number (RPN) was calculated for a C-Weekly and a PF-Weekly MLC QA program. The probability of occurrence was evaluated from statistical analyses of the C-Weekly MLC QA. RESULTS: The total number of failures for these 16,855 tests was 143 (0.9%): 39 (27.3%) for absolute MLC leaf position, 13 (9.1%) for interdigitation position, 9 (6.3%) for static gantry picket fence, 2 (1.4%) for minimum leaf-gap setting, and 80 (55.9%) for VMAT delivery. RPN scores for PF-Weekly MLC QA ranged from 60 to 192 and from 48 to 96 for C-Weekly MLC QA. CONCLUSION: RPNs for the 5 failure modes of MLC QA tests were quantitatively determined and analyzed. A comprehensive weekly MLC QA is imperative to lower the RPNs of the 5 failure modes to the desired level (<125); those from the PF-Weekly MLC QA program were found to be higher (>125). This supports the clinical necessity for comprehensive weekly MLC QA.

Isotretinoin treatment of 12 dogs with epitheliotropic lymphoma.

BACKGROUND: Epitheliotropic lymphoma is an uncommon cutaneous malignancy of T lymphocytes. Limited information is available regarding the treatment and outcome of dogs with this disease. OBJECTIVES: To evaluate the treatment outcome and toxicity profile of isotretinoin in dogs with epitheliotropic lymphoma. ANIMALS: Twelve dogs with a diagnosis of epitheliotropic lymphoma were included. MATERIALS AND METHODS: A medical database was searched for dogs diagnosed with epitheliotropic lymphoma and treated with isotretinoin between 2010 and 2021. Diagnosis, treatment details and tumour response were recorded for 12 dogs. RESULTS: All lesions resolved in four of 12 (33%) treated dogs. Lesions visibly improved in a further three dogs, giving a response rate of 58%. Two dogs' lesions remained unchanged and three progressed despite therapy. Adverse effects occurred in three dogs (25%), all of which were rapidly resolving or not affecting quality of life. CONCLUSION: Isotretinoin treatment was a well-tolerated and effective treatment for canine epitheliotropic lymphoma.

Contexte - Le lymphome épithéliotrope est une tumeur maligne cutanée peu fréquente des lymphocytes T. Peu d'informations sont disponibles concernant le traitement et les résultats des chiens atteints de cette maladie. Objectifs - Évaluer les résultats du traitement et le profil de toxicité de l'isotrétinoïne chez les chiens atteints de lymphome épithéliotrope. Animaux - Douze chiens avec un diagnostic de lymphome épithéliotrope ont été inclus. Matériels et méthodes - Une base de données médicale a été recherchée pour les chiens diagnostiqués avec un lymphome épithéliotrope et traités à l'isotrétinoïne entre 2010 et 2021. Le diagnostic, les détails du traitement et la réponse tumorale ont été enregistrés pour 12 chiens. Résultats - Toutes les lésions ont disparu chez quatre des 12 (33 %) chiens traités. Les lésions se sont visiblement améliorées chez trois autres chiens, donnant un taux de réponse de 58 %. Les lésions de deux chiens sont restées stables et trois ont progressé malgré la thérapie. Des effets indésirables sont survenus chez trois chiens (25 %), qui se résolvaient tous rapidement ou n'affectaient pas la qualité de vie. Conclusion - Le traitement à l'isotrétinoïne a été un traitement bien toléré et efficace du lymphome épithéliotrope canin.

Introducción - El linfoma epiteliotrópico es una neoplasia maligna cutánea poco frecuente de linfocitos T. Se dispone de información limitada sobre el tratamiento y el resultado del mismo en perros con esta enfermedad. Objetivos- evaluar el resultado del tratamiento y el perfil de toxicidad de la isotretinoína en perros con linfoma epiteliotrópico. Animales- se incluyeron 12 perros con diagnóstico de linfoma epiteliotrópico. Materiales y métodos- se buscó en una base de datos médica perros diagnosticados con linfoma epiteliotrópico y tratados con isotretinoína entre 2010 y 2021. Se reciplaron datos del diagnóstico, los detalles del tratamiento y la respuesta del tumor en 12 perros. Resultados- todas las lesiones se resolvieron en cuatro de 12 (33 %) perros tratados. Las lesiones mejoraron visiblemente en otros tres perros, con una tasa de respuesta del 58%. Las lesiones de dos perros permanecieron estables y tres progresaron a pesar de la terapia. Efectos adversos fueron reportados en tres perros (25%), todos los cuales se resolvieron rápidamente o no afectaron a la calidad de vida. Conclusión- el tratamiento con isotretinoína fue bien tolerado y eficaz para el linfoma epiteliotrópico canino.

Contexto - O linfoma epiteliotrópico é uma neoplasia cutânea de linfócitos T incomum. As informações disponíveis sobre o tratamento e evolução de cães com essa doença são limitadas. Objetivos - Avaliar a resposta ao tratamento e o perfil de toxicidade da isotretinoína em cães com linfoma epiteliotrópico. Animais - Doze cães com linfoma epiteliotrópico foram incluídos. Materiais e métodos - Pesquisou-se em um banco de dados médico os cães diagnosticados com linfoma epiteliotrópico e tratados com isotretinoína entre 2010 e 2021. Diagnóstico, detalhes do tratamento e resposta tumoral foram registrados para 12 cães. Resultados - Todas as lesões se resolveram em quatro de 12 (33%) cães. As lesões melhoraram visivelmente em outros três cães, gerando uma taxa de resposta de 58%. As lesões de dois cães permaneceram estáveis e três progrediram apesar da terapia. Ocorreram efeitos adversos em três cães (25%), mas todos apresentaram resolução rápida ou não tiveram alteração na qualidade de vida. Conclusão - O tratamento com isotretinoína foi bem tolerado e eficaz para o linfoma epiteliotrópico canino.

Electrochemotherapy as a treatment option for feline nasal melanoma.

CASE SUMMARY: A 4-year-old domestic shorthair cat presented to North Downs Specialist Referrals for treatment of a 7 mm melanoma of the nasal planum. Two treatments of electrochemotherapy using intravenous bleomycin as a chemotherapeutic agent were administered. The tumour was no longer visible after treatment. At the 292-day follow-up there was no recurrence at the site and the patient was clinically well. RELEVANCE AND NOVEL INFORMATION: There are few data concerning the outcomes of cats with non-ocular feline melanomas and there are currently minimal descriptions in the literature of electrochemotherapy as a treatment option. The available data suggest that nasal melanoma may have a worse prognosis, and that melanomas are locally invasive and have a high propensity for metastasis. The current most effective means for local control is surgery with wide margins. Given the location in this case, this would have required nasal planectomy, while electrochemotherapy provided an effective and possibly more attractive alternative.

Toxicity of zoledronic acid after intravenous administration: A retrospective study of 95 dogs.

BACKGROUND: There is a paucity of veterinary literature on the safety or outcome of zoledronic acid (ZA) use in dogs for either bone pain or hypercalcemia. HYPOTHESIS/OBJECTIVES: The primary aim was to report the adverse events in dogs receiving intravenous administration of ZA. ANIMALS: Ninety-five dogs with ZA use. METHODS: A retrospective cohort study was performed; all dogs that received at least 1 dose of ZA and had a serum biochemistry profile performed before and after treatment were reviewed. Diagnosis, indication for treatment, adverse events and survival times were recorded. RESULTS: Ninety-five dogs met the inclusion criteria. Thirty-one (33%) received multiple intravenous infusions of ZA (range, 2-7), making a total of 166 administrations in all dogs. The dose range was 0.13 to 0.32 mg/kg, given at intervals of 4 to 6 weeks. Thirteen adverse events were recorded in 10 dogs: azotemia (n = 8), vomiting (n = 2), pancreatitis (n = 1), cutaneous ulceration (n = 1), and diarrhea (n = 1). Zoledronic acid could not be confirmed as the cause of azotemia in any case. The change in serum creatinine concentration from dose to dose was not related to the total dose received (P = .46). Five dogs (5%) changed Veterinary Comparative Oncology Group Common Terminology Criteria (VCOG-CTAE) renal/genitourinary grade after administration of ZA; their total dose 0.4 mg/kg (range, 0.26-0.66) was not significantly different to the group which did not change VCOG-CTAE renal/genitourinary grade 0.35 mg/kg (range, 0.2-1.50; P = .93). CONCLUSIONS AND CLINICAL IMPORTANCE: Multiple doses of ZA were well tolerated in dogs within this study. A small number of dogs developed progressive azotemia which was not associated with cumulative dose.

Comparison of the dosimetric accuracy of proton breast treatment plans delivered with SGRT and CBCT setups.

PURPOSE: To compare the dosimetric accuracy of surface-guided radiation therapy (SGRT) and cone-beam computed tomography (CBCT) setups in proton breast treatment plans. METHODS: Data from 30 patients were retrospectively analyzed in this IRB-approved study. Patients were prescribed 4256-5040 cGy in 16-28 fractions. CBCT and AlignRT (SGRT; Vision RT Ltd.) were used for treatment setup during the first three fractions, then daily AlignRT and weekly CBCT thereafter. Each patient underwent a quality assurance CT (QA-CT) scan midway through the treatment course to assess anatomical and dosimetric changes. To emulate the SGRT and CBCT setups during treatment, the planning CT and QA-CT images were registered in two ways: (1) by registering the volume within the CTs covered by the CBCT field of view; and (2) by contouring and registering the surface surveyed by the AlignRT system. The original plan was copied onto these two datasets and the dose was recalculated. The clinical treatment volume (CTV): V95% ; heart: V25Gy , V15Gy , and mean dose; and ipsilateral lung: V20Gy , V10Gy , and V5Gy , were recorded. Multi and univariate analyses of variance were performed to assess the differences in dose metric values between the planning CT and the SGRT and CBCT setups. RESULTS: The CTV V95% and lung V20Gy , V10Gy , and V5Gy dose metrics were all significantly (p < 0.01) lower on the QA-CT in both the CBCT and SGRT setup. The differences were not clinically significant and were, on average, 1.4-1.6% lower for CTV V95% and 1.8%-6.0% lower for the lung dose metrics. When comparing the lung and CTV V95% dose metrics between the CBCT and SGRT setups, no significant difference was observed. This indicates that the SGRT setup provides similar dosimetric accuracy as CBCT. CONCLUSION: This study supports the daily use of SGRT systems for the accurate dose delivery of proton breast treatment plans.

Gene Expression Profiling of B Cell Lymphoma in Dogs Reveals Dichotomous Metabolic Signatures Distinguished by Oxidative Phosphorylation.

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health.

Technical Note: A fast inverse direct aperture optimization algorithm for volumetric-modulated arc therapy.

PURPOSE: In a recent article, our group proposed a fast direct aperture optimization (DAO) algorithm for fixed-gantry intensity-modulated radiation therapy (IMRT) called fast inverse direct aperture optimization (FIDAO). When tested on fixed-gantry IMRT plans, we observed up to a 200-fold increase in the optimization speed. Compared to IMRT, rotational volumetric-modulated arc therapy (VMAT) is a much larger optimization problem and has many more delivery constraints. The purpose of this work is to extend and evaluate FIDAO for inverse planning of VMAT plans. METHODS: A prototype FIDAO algorithm for VMAT treatment planning was developed in MATLAB using the open-source treatment planning toolkit matRad (v2.2 dev_VMAT build). VMAT treatment plans using one 3600 arc were generated on the AAPM TG-119 phantom, as well as sample clinical liver and prostate cases. The plans were created by first performing fluence map optimization on 28° equispaced beams, followed by aperture sequencing and arc sequencing with a gantry angular sampling rate of 4°. After arc sequencing, a copy of the plan underwent DAO using the prototype FIDAO algorithm, while another copy of the plan underwent DAO using matRad's DAO method, which served as the conventional algorithm. RESULTS: Both algorithms achieved similar plan quality, although the FIDAO plans had considerably fewer hot spots in the unspecified normal tissue. The optimization time (number of iterations) for FIDAO and the conventional DAO algorithm, respectively, were: 65 s (245) vs 602 s (275) in the TG-119 phantom case; 25 s (85) vs 803 s (159) in the liver case; and 99 s (174) vs 754 s (149) in the prostate case. CONCLUSIONS: This study demonstrated promising speed enhancements in using FIDAO for the direct aperture optimization of VMAT plans.

Clozapine toxicity: a cautionary palliative care tale.

OBJECTIVE: This case report presents an unusual case of clozapine toxicity secondary to reduced smoking habit mimicking a patient approaching end of life. METHODS: It is a cautionary tale for palliative care specialists, perhaps unaware of the effect of cigarette smoke on metabolism of this antipsychotic, to be aware of. RESULTS: Following specialist advice and change of antipsychotic medication, this patient's condition improved to the point that he was discharged from the hospice. CONCLUSION: Palliative care specialists should be aware that reducing cigarette consumption can alter metabolism of clozapine, potentially causing drug accumulation and toxicity with features which mimic deterioration towards end of life. Specialist advice should be sought in such a situation.

A fast inverse direct aperture optimization algorithm for intensity-modulated radiation therapy.

PURPOSE: The goal of this work was to develop and evaluate a fast inverse direct aperture optimization (FIDAO) algorithm for IMRT treatment planning and plan adaptation. METHODS: A previously proposed fluence map optimization algorithm called fast inverse dose optimization (FIDO) was extended to optimize the aperture shapes and weights of IMRT beams. FIDO is a very fast fluence map optimization algorithm for IMRT that finds the global minimum using direct matrix inversion without unphysical negative beam weights. In this study, an equivalent second-order Taylor series expansion of the FIDO objective function was used, which allowed for the objective function value and gradient vector to be computed very efficiently during direct aperture optimization, resulting in faster optimization. To evaluate the speed gained with FIDAO, a proof-of-concept algorithm was developed in MATLAB using an interior-point optimization method to solve the reformulated aperture-based FIDO problem. The FIDAO algorithm was used to optimize four step-and-shoot IMRT cases: on the AAPM TG-119 phantom as well as a liver, prostate, and head-and-neck clinical cases. Results were compared with a conventional DAO algorithm that uses the same interior-point method but using the standard formulation of the objective function and its gradient vector. RESULTS: A substantial gain in optimization speed was obtained with the prototype FIDAO algorithm compared to the conventional DAO algorithm while producing plans of similar quality. The optimization time (number of iterations) for the prototype FIDAO algorithm vs the conventional DAO algorithm was 0.3 s (17) vs 56.7 s (50); 2.0 s (28) vs 134.1 s (57); 2.5 s (26) vs 180.6 s (107); and 6.7 s (20) vs 469.4 s (482) in the TG-119 phantom, liver, prostate, and head-and-neck examples, respectively. CONCLUSIONS: A new direct aperture optimization algorithm based on FIDO was developed. For the four IMRT test cases examined, this algorithm executed approximately 70-200 times faster without compromising the IMRT plan quality.

Patient-specific calibration of cone-beam computed tomography data sets for radiotherapy dose calculations and treatment plan assessment.

PURPOSE: In this work, we propose a new method of calibrating cone beam computed tomography (CBCT) data sets for radiotherapy dose calculation and plan assessment. The motivation for this patient-specific calibration (PSC) method is to develop an efficient, robust, and accurate CBCT calibration process that is less susceptible to deformable image registration (DIR) errors. METHODS: Instead of mapping the CT numbers voxel-by-voxel with traditional DIR calibration methods, the PSC methods generates correlation plots between deformably registered planning CT and CBCT voxel values, for each image slice. A linear calibration curve specific to each slice is then obtained by least-squares fitting, and applied to the CBCT slice's voxel values. This allows each CBCT slice to be corrected using DIR without altering the patient geometry through regional DIR errors. A retrospective study was performed on 15 head-and-neck cancer patients, each having routine CBCTs and a middle-of-treatment re-planning CT (reCT). The original treatment plan was re-calculated on the patient's reCT image set (serving as the gold standard) as well as the image sets produced by voxel-to-voxel DIR, density-overriding, and the new PSC calibration methods. Dose accuracy of each calibration method was compared to the reference reCT data set using common dose-volume metrics and 3D gamma analysis. A phantom study was also performed to assess the accuracy of the DIR and PSC CBCT calibration methods compared with planning CT. RESULTS: Compared with the gold standard using reCT, the average dose metric differences were ≤ 1.1% for all three methods (PSC: -0.3%; DIR: -0.7%; density-override: -1.1%). The average gamma pass rates with thresholds 3%, 3 mm were also similar among the three techniques (PSC: 95.0%; DIR: 96.1%; density-override: 94.4%). CONCLUSIONS: An automated patient-specific calibration method was developed which yielded strong dosimetric agreement with the results obtained using a re-planning CT for head-and-neck patients.

Does place of death vary by deprivation for patients known to specialist palliative care services?

OBJECTIVES: Referral to, and usage of, specialist palliative care (SPC) services are not equitable and social deprivation may be a contributory factor in this. Deprivation may also affect the place of death of patients with cancer. No study, however, has investigated whether inequalities persist following referral to SPC services. This study investigates whether place of death varies by deprivation for patients known to SPC services. METHODS: Place of death and postcode were obtained for 485 consecutive patients known to SPC services within NHS Lothian who died in 2014-2015. From this information, deprivation quintile (DQ) was derived using the Scottish Index of Multiple Deprivation (SIMD) database and place of death compared between DQs and analysed statistically. RESULTS: Across all DQs, patients known to SPC services were more likely to die in the hospice than at home or in hospital. There was, however, a small but statistically significant difference in the ratio of hospital deaths compared to hospice deaths between the DQs, with higher death rates in hospital for the most deprived compared to the least deprived and higher death rates in the hospice for the least deprived compared to the most deprived. CONCLUSIONS: This study suggests that even after referral to specialist palliative care services variation in place of death by deprivation persists. Greater deprivation is associated with increased likelihood of dying in hospital and decreased likelihood of dying in a hospice, although no difference was noted for home deaths.

Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 µg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 µg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 µg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.

Evaluation of unified intensity-modulated arc therapy for the radiotherapy of head-and-neck cancer.

PURPOSE: Recently our group developed a unified intensity-modulated arc therapy (UIMAT) technique which allows for the simultaneous inverse-optimization and the combined delivery of volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). The aim of this study was to evaluate the dosimetric benefits of UIMAT plans for radiation treatment of complex head-and-neck cancer cases. METHODS AND MATERIALS: A retrospective treatment planning study was performed on 30 head-and-neck cases, 15 of which were treated clinically with VMAT while the other 15 were treated with step-and-shoot IMRT. These cases were re-planned using our UIMAT technique and the results were compared with the clinically delivered plans. Plans were assessed in terms of clinically relevant metrics describing target volume coverage, dose conformity, and the sparing of organs at risk. RESULTS: When compared to stand-alone VMAT or IMRT, UIMAT plans offered slightly better tumor volume coverage (Median D95: 98.1% vs. 97.5%, p=0.01) and similar dose conformity (Median CI: 0.69 vs. 0.69, p=0.09). More significantly, UIMAT plans had substantially lower doses to all organs at risk, including the spinal cord (Median D2%: 29.9Gy vs. 35.6Gy, p<0.01), brainstem (Median D2%: 21.2Gy vs. 25.6Gy, p<0.01), left parotid (Median DMean: 26.1Gy vs. 28.0Gy, p<0.01), and right parotid (Median DMean: 23.6Gy vs. 27.2Gy, p<0.01). The reduction in OAR doses did not result from the redistribution of dose to unspecified tissue. Furthermore, UIMAT plans can be delivered with comparable delivery times to VMAT (Median time: 135s vs. 168s, p=0.394) but with fewer monitor units (Median MU: 486 vs. 635, p<0.01). CONCLUSIONS: Compared to stand-alone IMRT or VMAT, UIMAT was demonstrated to have a dosimetric advantage for the radiation treatment of head-and-neck cancer.

Feasibility of a unified approach to intensity-modulated radiation therapy and volume-modulated arc therapy optimization and delivery.

PURPOSE: To study the feasibility of unified intensity-modulated arc therapy (UIMAT) which combines intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) optimization and delivery to produce superior radiation treatment plans, both in terms of dose distribution and efficiency of beam delivery when compared with either VMAT or IMRT alone. METHODS: An inverse planning algorithm for UIMAT was prototyped within the pinnacle treatment planning system (Philips Healthcare). The IMRT and VMAT deliveries are unified within the same arc, with IMRT being delivered at specific gantry angles within the arc. Optimized gantry angles for the IMRT and VMAT phases are assigned automatically by the inverse optimization algorithm. Optimization of the IMRT and VMAT phases is done simultaneously using a direct aperture optimization algorithm. Five treatment plans each for prostate, head and neck, and lung were generated using a unified optimization technique and compared with clinical IMRT or VMAT plans. Delivery verification was performed with an ArcCheck phantom (Sun Nuclear) on a Varian TrueBeam linear accelerator (Varian Medical Systems). RESULTS: In this prototype implementation, the UIMAT plans offered the same target dose coverage while reducing mean doses to organs at risk by 8.4% for head-and-neck cases, 5.7% for lung cases, and 3.5% for prostate cases, compared with the VMAT or IMRT plans. In addition, UIMAT can be delivered with similar efficiency as VMAT. CONCLUSIONS: In this proof-of-concept work, a novel radiation therapy optimization and delivery technique that interlaces VMAT or IMRT delivery within the same arc has been demonstrated. Initial results show that unified VMAT/IMRT has the potential to be superior to either standard IMRT or VMAT.

Dosimetric planning study of respiratory-gated volumetric modulated arc therapy for early-stage lung cancer with stereotactic body radiation therapy.

PURPOSE: To evaluate the dosimetric potential of respiratory-gated volumetric modulated arc therapy (VMAT) to reduce the dose to normal lung when treating early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Twenty patients with inoperable stage I/II NSCLC with motion greater than 5 mm were retrospectively planned with 4-dimensional computed tomography-based gated and nongated VMAT. Each plan was optimized using two 225° arcs with 10-MV flattening filter-free beams with maximum dose rate of 2400 MU/min. A host script was generated and used to optimize all 40 plans to minimize dosimetric bias. The main dosimetric parameters compared were percent volume of the lung receiving 20 Gy or more (V(20Gy)) and the absolute volume of lung minus the internal tumor volume receiving at least 50% of the prescription dose for normal lung (V(50%)). Other parameters considered were the maximum dose 2 cm from the planning target volume (D(2cm)), percent volume of the contralateral lung receiving 5 Gy or more (V(5Gy)), mean lung dose, maximum dose to normal structures, and monitor units. RESULTS: There was a significant decrease in both parameters for the normal lung with gated VMAT. V(20Gy), predictive for pneumonitis, decreased from (6.05 ± 2.06%) to (5.25 ± 1.75%) (P = .00009) and the absolute volume of lung minus the internal tumor volume receiving at least 50% of the prescription dose decreased from (158.17 ± 61.12 cm(3)) to (125.71 ± 49.46 cm(3)) (P = .00002). Also, there was a significant decrease in D(2cm), contralateral V(5Gy), mean lung dose, and monitor units. CONCLUSIONS: Respiratory-gated VMAT has the potential to reduce the dose to normal lung when treating early-stage NSCLC with SBRT for tumor motion greater than 5 mm.

Selection of optimal prostate specific antigen cutoffs for early detection of prostate cancer: receiver operating characteristic curves.

A prospective clinical trial of prostate cancer screening was conducted at 6 university centers including 6,630 men 50 years old or older who underwent a serum prostate specific antigen (PSA) determination and digital rectal examination. Biopsies were performed if the PSA level was greater than 4.0 ng./ml. (Hybritech Tandem assay) or digital rectal examination was suspicious for cancer. We evaluated the effect on biopsy rate and cancer detection if the cutoff value was shifted from 4.0 to age-specific reference ranges recommended in the literature. In men 50 to 59 years old with normal digital rectal examination findings a decrease from 4.0 to 3.5 ng./ml. would have resulted in a 45% increase in the number of biopsies (39 of 87) and a projected 15% increase in cancer detection. An increase from 4.0 to 4.5 ng./ml. in men 60 to 69 years old would result in 15% fewer biopsies (35 of 238) and would miss 8% of the organ confined tumors (2 of 25). Increasing the cutoff to 6.5 ng./ml. in men 70 years old or older would result in 44% fewer biopsies (70 of 159) and would miss 47% of the organ confined cancers (7 of 15). The number of biopsies performed for each cancer detected with a PSA level of greater than 4.0 ng./ml. remains constant across age groupings, which suggests that the cutoff of 4.0 ng./ml. does not need to be altered in the older men, since it is apparently unaffected by the simultaneously increasing prevalence of benign prostatic hyperplasia and cancer with age. We conclude that a serum PSA concentration of 4.0 ng./ml. should be used as a general guideline for biopsy in all age groups.

Accuracy of digital rectal examination and transrectal ultrasonography in localizing prostate cancer.

Not all prostate cancers are sonographically hypoechoic or palpable on digital rectal examination, and suspicious areas on transrectal prostatic ultrasonography or digital rectal examination often are not cancer. We present quadrant biopsy results from a multicenter prostate cancer screening study in which men were evaluated with prostate specific antigen (PSA) and digital rectal examination. If the PSA level was elevated (greater than 4.0 ng./ml., Hybritech Tandem assay) or digital rectal examination was suspicious quadrant biopsies were performed. Biopsy specimens were labeled separately, and histological findings were correlated by quadrant with the findings on ultrasonography and digital rectal examination. Of the 6,630 subjects enrolled into the study 16% were biopsied. Of 1,002 quadrants that were suspicious on digital rectal examination 110 (11%) had cancer, while 308 of 418 quadrants containing cancer (74%) were not suspicious on digital rectal examination. Of 855 quadrants that were sonographically suspicious 153 (18%) had cancer, while 282 of 435 quadrants containing cancer (65%) were not sonographically suspicious. Of 225 patients with cancer 137 (61%) would have been missed if only the exact site of the palpable induration had been biopsied. Of 251 patients with cancer 131 (52%) would have been missed if only the exact site of the hypoechoic lesion had been biopsied. We conclude that digital rectal examination and transrectal ultrasonography have limited accuracy in identifying and localizing prostate cancer. Our study emphasizes the importance of obtaining systematic biopsies if the PSA level is elevated, even in the absence of digital rectal examination or ultrasound anomalies.

Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men.

To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandem-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 micrograms/l or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 micrograms/l, 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 micrograms/l or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.