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PURPOSE: To report disease control and treatment-related side effects among adult patients with craniopharyngioma treated with radiotherapy. METHODS: We performed a single-institution review of adult patients (> 21 years old) with craniopharyngioma treated with radiotherapy either definitively or postoperatively for gross residual disease. We report disease control, survival, and radiotherapy-related side effects. RESULTS: A total of 49 adult patients with craniopharyngioma were included, 27 of whom were treated at initial presentation and 22 for recurrent disease following initial surgery and observation. Overall, 77% received radiotherapy postoperatively (either after primary surgery or surgery for recurrence). With a median clinical and radiographic follow-up of 4.2 (range, 0.4-21.6) years and 3.0 (range, 0-21.5) years, the 5- and 10-year local control rates were 100 and 94%, respectively. The 5- and 10-year overall survival rates were 80 and 66%, respectively. Eleven percent of patients experienced grade 2 vision deterioration and 18% suffered grade 2 endocrinopathies following radiotherapy. CONCLUSIONS: Radiotherapy provides excellent disease control with acceptable toxicity among adult patients with craniopharyngioma. These data support the use of fractionated radiotherapy in adult patients with recurrent or gross residual disease after surgery. For inoperable patients or those with moderate or high surgical risk to neurologic and/or vascular structures, we advocate for limited surgical resection and postoperative radiotherapy to balance optimal tumor control with tumor- and treatment-related morbidity.
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Craneofaringioma , Neoplasias Hipofisarias , Adulto , Craneofaringioma/radioterapia , Craneofaringioma/cirugía , Humanos , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Neoplasia Residual/cirugía , Neoplasias Hipofisarias/radioterapia , Neoplasias Hipofisarias/cirugía , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response. METHODS: We analyzed 14 adult patients (≥ 22 years old). All patients had gross disease at the time of radiotherapy. Five were treated for de novo disease and 9 for recurrent disease. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2-54 GyRBE). Weekly magnetic resonance imaging (MRI) helped to evaluate tumor changes during radiotherapy. RESULTS: With median clinical and radiographic follow-up of 29 and 26 months, respectively, the 3-year local control and overall survival rates were both 100%. There were no grade 3 or greater acute or late radiotherapy-related side effects. There was no radiotherapy-related vision loss or optic neuropathy. No patients required intervention or treatment replanning due to tumor changes during radiotherapy. Two patients experienced transient cyst expansion at their first post-radiotherapy MRI. Both patients were followed closely clinically and radiographically and had subsequent dramatic tumor/cyst regression, requiring no interventions. CONCLUSIONS: Our data support the safety and efficacy of proton therapy in the treatment of adult craniopharyngioma as part of primary or salvage treatment. We recommend early consideration of radiotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03224767.
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Craneofaringioma/mortalidad , Neoplasias Hipofisarias/mortalidad , Terapia de Protones/mortalidad , Radioterapia Conformacional/mortalidad , Adulto , Craneofaringioma/patología , Craneofaringioma/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/radioterapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: The treatment of centrally-located early-stage non-small cell lung cancer (NSCLC) with image-guided stereotactic body radiotherapy (SBRT) is challenging due to the proximity of critical normal structures to the tumor target. The purpose of this study was to report the results of our experience in treating centrally-located early-stage NSCLC with hypofractionated proton therapy (PT). MATERIAL AND METHODS: Between 2009 and 2018, 23 patients with T1-T2N0M0 NSCLC (T1, 46%; T2, 54%) were treated with image-guided hypofractionated double-scattering PT. The median age at the time of treatment was 74 years (range, 58-88). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. All patients were treated with 60 GyRBE in 10 fractions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks. RESULTS: Median follow-up for all patients was 3.2 years (range, 0.2-9.2 years). Overall survival rates at 3 and 5 years were 81% and 50% (95% CI, 27-79%), respectively. Cause-specific survival rates at 3 and 5 years were 81% and 71% (95% CI, 46-92%). The 3-year local, regional, and distant control rates were 90%, 81%, and 87%, respectively. Three patients (13%) experienced local recurrences as their first recurrence, at a median time of 28 months from completion of radiation (range, 18-61 months). Two patients (9%) experienced late grade 3 toxicities, including 1 patient who developed a bronchial stricture that required stent placement. CONCLUSION: Image-guided hypofractionated PT for centrally-located early-stage NSCLC provides excellent local control with low rates of grade ≥3 toxicities. For tumors in sensitive locations, PT may provide safer treatment than photon-based treatments due to its dosimetric advantages.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia de Protones , Radiocirugia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND: We compared target and normal tissue dosimetric indices between ultra-hypofractionated passively scattered proton radiotherapy and stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. MATERIAL AND METHODS: Ten patients were treated definitively for localized prostate cancer with SBRT to a dose of 36.25 Gy in 5 fractions prescribed to a volume encompassing the prostate only. Dose-volume constraints were applied to the rectum, bladder, penile bulb, femoral heads, and prostatic and membranous urethra. Three-field passively scattered proton plans were retrospectively generated using target volumes from the same patients. Dosimetric indices were compared between the SBRT and proton plans using the Wilcoxon signed rank test. RESULTS: All dose constraints were achieved using both ultra-hypofractionated passively scattered proton and SBRT planning. Proton plans demonstrated significant improvement over SBRT in mean dose delivered to the penile bulb (5.2 CGE vs. 11.4 Gy; p=0.002), rectum (6.7 CGE vs. 10.6 Gy; p=0.002), and membranous urethra (32.2 CGE vs. 34.4 Gy; p=0.006) with improved target homogeneity resulting in a significant reduction in hot spots and volumes of tissue exposed to low doses of radiation. Compared to proton planning, SBRT planning resulted in significant improvement in target conformality with a mean index of 1.17 versus 1.72 (p=0.002), resulting in a dose reduction to the volume of bladder receiving more than 90% of the PD (V32.6, 7.5% vs. 15.9%; p=0.01) and mean dose to the left (7.1 Gy vs. 10.4 CGE; p=0.004) and right (4.0 Gy vs. 10.9 CGE; p=0.01) femoral heads. CONCLUSION: Target and normal tissue dose constraints for ultra-hypofractionated definitive radiotherapy of localized prostate cancer are readily achieved using both CK SBRT and passively scattered proton-based therapy suggesting feasibility of either modality.
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Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Terapia de Protones/métodos , Hipofraccionamiento de la Dosis de Radiación , Radiocirugia/métodos , Cabeza Femoral , Humanos , Masculino , Órganos en Riesgo , Pene , Neoplasias de la Próstata/patología , Planificación de la Radioterapia Asistida por Computador , Recto , Uretra , Vejiga UrinariaRESUMEN
BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). MATERIAL AND METHODS: Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. RESULTS: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. CONCLUSION: In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.
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Quimioradioterapia/métodos , Neoplasias Pulmonares/terapia , Terapia de Protones/métodos , Dosificación Radioterapéutica , Carcinoma Pulmonar de Células Pequeñas/terapia , Anciano , Quimioradioterapia/efectos adversos , Florida , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Terapia de Protones/efectos adversos , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/etiología , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/epidemiología , Carcinoma Pulmonar de Células Pequeñas/patología , Factores de TiempoRESUMEN
BACKGROUND: To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. MATERIAL AND METHODS: From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. RESULTS: Median follow-up for all patients was 11 (range 5-36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. DISCUSSION: Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.
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Adenocarcinoma/terapia , Ampolla Hepatopancreática , Quimioradioterapia/efectos adversos , Neoplasias del Conducto Colédoco/terapia , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Enfermedades Gastrointestinales/epidemiología , Neoplasias Pancreáticas/terapia , Terapia de Protones/efectos adversos , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Administración Oral , Anciano , Ampolla Hepatopancreática/efectos de los fármacos , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/efectos de la radiación , Capecitabina , Neoplasias del Conducto Colédoco/epidemiología , Neoplasias del Conducto Colédoco/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Enfermedades Gastrointestinales/etiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Terapia de Protones/métodos , Traumatismos por Radiación/epidemiología , Dosificación Radioterapéutica , Estudios RetrospectivosAsunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Glioma/diagnóstico , Glioma/radioterapia , Imagen por Resonancia Magnética , Terapia de Protones , Adolescente , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/patología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Glioma/epidemiología , Glioma/patología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Monitoreo Fisiológico/métodos , Pronóstico , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Retrospectivos , Carga Tumoral/efectos de la radiaciónRESUMEN
PURPOSE: The objective of this study was to report the clinical results for a patient with a post-traumatic osteoarticular defect of the lateral femoral condyle treated with unicondylar osteoarticular allograft reconstruction. METHOD: We describe the case with a massive osteoarticular loss of the lateral femoral condyle combined with a grade IIIA open distal femoral diaphyesal fracture. The patient underwent unicondylar osteoarticular reconstruction with an allogenic fresh-frozen condyle. RESULTS: There were no complications after the reconstructive procedure. At the five year follow-up, the patient showed a favorable clinical outcome with a full range of motion of the knee joint. Degenerative changes were seen in the graft compartment, but they did not cause serious functional limitations. CONCLUSION: Unicondylar allograft reconstruction appears to be a surgical option for patients who suffer from a post-traumatic distal femoral osteoarticular defect in which only one condyle is absent or severely damaged.
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Trasplante Óseo/métodos , Epífisis/cirugía , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas/efectos adversos , Traumatismos de la Rodilla/cirugía , Procedimientos de Cirugía Plástica/métodos , Accidentes de Tránsito , Clavos Ortopédicos , Epífisis/lesiones , Fijadores Externos , Fracturas del Fémur/diagnóstico por imagen , Estudios de Seguimiento , Fijación Interna de Fracturas/métodos , Curación de Fractura/fisiología , Humanos , Puntaje de Gravedad del Traumatismo , Traumatismos de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Radiografía , Rango del Movimiento Articular/fisiología , Recuperación de la Función , Reoperación , Medición de Riesgo , Trasplante HomólogoRESUMEN
BACKGROUND: Although there are some controversies regarding whole pelvic radiation therapy (WPRT) due to its gastrointestinal and hematologic toxicities, it is considered for patients with gynecological, rectal, and prostate cancer. To effectively spare organs-at-risk (OAR) doses using multi-leaf collimator (MLC)'s optimal segments, potential dosimetric benefits in volumetric modulated arc therapy (VMAT) using a half-beam technique (HF) were investigated for WPRT. METHODS: While the size of a fully opened field (FF) was decided to entirely include a planning target volume in all beam's eye view across arc angles, the HF was designed to use half the FF from the isocenter for dose optimization. The left or the right half of the FF was alternatively opened in VMAT-HF using a pair of arcs rotating clockwise and counterclockwise. Dosimetric benefits of VMAT-HF, presented with dose conformity, homogeneity, and dose-volume parameters in terms of modulation complex score, were compared to VMAT optimized using the FF (VMAT-FF). Consequent normal tissue complication probability (NTCP) by reducing the irradiated volumes was evaluated as well as dose-volume parameters with statistical analysis for OAR. Moreover, beam-on time and MLC position precision were analyzed with log files to assess plan deliverability and clinical applicability of VMAT-HF as compared to VMAT-FF. RESULTS: While VMAT-HF used 60%-70% less intensity modulation complexity than VMAT-FF, it showed superior dose conformity. The small intestine and colon in VMAT-HF showed a noticeable reduction in the irradiated volumes of up to 35% and 15%, respectively, at an intermediate dose of 20-45 Gy. The small intestine showed statistically significant dose sparing at the volumes that received a dose from 15 to 45 Gy. Such a dose reduction for the small intestine and colon in VMAT-HF presented a significant NTCP reduction from that in VMAT-FF. Without sacrificing the beam delivery efficiency, VMAT-HF achieved effective OAR dose reduction in dose-volume histograms. CONCLUSIONS: VMAT-HF led to deliver conformal doses with effective gastrointestinal-OAR dose sparing despite using less modulation complexity. The dose of VMAT-HF was delivered with the same beam-on time with VMAT-FF but precise MLC leaf motions. The VMAT-HF potentially can play a valuable role in reducing OAR toxicities associated with WPRT.
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The objective was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal proton therapy (3DCPT) in the treatment of cervical cancer. In particular, each technique's ability to spare pelvic bone marrow (PBM) was of primary interest in this study. A total of six cervical cancer patients (3 postoperative and 3 intact) were planned and analyzed. All plans had uniform 1.0 cm CTV-PTV margin and satisfied the 95% PTV with 100% isodose (prescription dose = 45 Gy) coverage. Dose-volume histograms (DVH) were analyzed for comparison. The overall PTV and PBM volumes were 1035.9 ± 192.2 cc and 1151.4 ± 198.3 cc, respectively. In terms of PTV dose conformity index (DCI) and dose homogeneity index (DHI), 3DCPT was slightly superior to IMRT with 1.00 ± 0.001, 1.01 ± 0.02, and 1.10 ± 0.02, 1.13 ± 0.01, respectively. In addition, 3DCPT demonstrated superiority in reducing lower doses (i.e., V30 or less) to PBM, small bowel and bladder. Particularly in PBM, average V10 and V20 reductions of 10.8% and 7.4% (p = 0.001 and 0.04), respectively, were observed. However, in the higher dose range, IMRT provided better sparing (> V30). For example, in small bowel and PBM, average reductions in V45 of 4.9% and 10.0% (p = 0.048 and 0.008), respectively, were observed. Due to its physical characteristics such as low entrance dose, spread-out Bragg peak and finite particle range of protons, 3DCPT illustrated superior target coverage uniformity and sparing of the lower doses in PBM and other organs. Further studies are, however, needed to fully exploit the benefits of protons for general use in cervical cancer.
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Médula Ósea/efectos de la radiación , Imagenología Tridimensional , Huesos Pélvicos/efectos de la radiación , Terapia de Protones , Planificación de la Radioterapia Asistida por Computador , Radioterapia Conformacional , Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino/radioterapia , Femenino , Humanos , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: With an increasing number of proton centers capable of delivering pencil beam scanning (PBS), understanding the dosimetric differences in PBS compared to passively scattered proton therapy (PSPT) for pancreatic cancer is of interest. METHODS: Optimized PBS plans were retrospectively generated for 11 patients with locally advanced pancreatic cancer previously treated with PSPT to 59.4 Gy on a prospective trial. The primary tumor was targeted without elective nodal coverage. The same treatment couch, target coverage and normal tissue dose objectives were used for all plans. A Wilcoxon t-test was performed to compare various dosimetric points between the two plans for each patient. RESULTS: All target volume coverage goals were met in all PBS and passive scattering (PS) plans, except for the planning target volume (PTV) coverage goal (V100% >95%) which was not met in one PS plan (range, 81.8-98.9%). PBS was associated with a lower median relative dose (102.4% vs. 103.8%) to 10% of the PTV (P=0.001). PBS plans had a lower median duodenal V59.4 Gy (37.4% vs. 40.4%; P=0.014), lower small bowel median V59.4 Gy (0.11% vs. 0.37%; P=0.012), lower stomach median V59.4 Gy (0.01% vs. 0.1%; P=0.023), and lower median dose to 0.1 cc of the spinal cord {35.0 vs. 38.7 Gy [relative biological effectiveness (RBE)]; P=0.001}. Liver dose was higher in PBS plans for median V5 Gy (24.1% vs. 20.2%; P=0.032), V20 Gy (3.2% vs. 2.8%; P=0.010), and V25 Gy (2.6% vs. 2.2%; P=0.019). There was no difference in kidney dose between PBS and PS plans. CONCLUSIONS: Proton therapy for locally advanced pancreatic cancer using PBS was not clearly associated with clinically meaningful reductions in normal tissue dose compared to PS. Some statistically significant improvements in PTV coverage were achieved using PBS. PBS may offer improved conformality for the treatment of irregular targets, and further evaluation of PBS and PS incorporating elective nodal irradiation should be considered.
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PURPOSE: Evaluate clinical outcomes in patients with vestibular schwannoma (VS) treated with fractionated proton therapy (PT) at a single institution. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients treated with fractionated PT for definitive management of VS between November 2007 and December 2013 at our institution. No patient had received prior treatment for VS. Patients received 50.4 Gy in 28 fractions using passively scattered PT. Pretreatment and posttreatment hearing status, tumor dimensions, and cranial nerve V and VII function were evaluated. Hearing status was graded as nonserviceable or serviceable, defined as Gardner-Robertson grade I or II and the ability to use a telephone with the treated ear. Toxicities were prospectively evaluated using Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Fourteen patients with 14 lesions (8 men, 6 women) were included in the analysis. Median age at treatment was 60 years (range, 24-74 years). Median clinical follow-up for living patients was 68 months (range, 36-106 months). Mean maximal tumor dimension was 2.1 cm (range, 0.5-3.8 cm). Mean tumor volume was 6.4 cm3 (range, 0.3-16.0 cm3). One patient died of unrelated causes 5 months after treatment, and 2 had subsequent surgical resections due to radiographic and/or clinical progression. The actuarial 3-year local control rate was 85%. There were no cranial nerve V or VII injuries. Two of 6 patients (33%) with serviceable hearing at the time of treatment retained serviceable hearing. Three patients (21%) demonstrated radiographic tumor regression on brain magnetic resonance imaging after a median of 26 months (range, 2-113 months). No acute toxicity of grade 3 or above was reported. CONCLUSION: Fractionated PT for VS is well tolerated and provides good local control. Improvements in proton delivery techniques and patient selection may enable improved outcomes.
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Acetabular fractures can be treated with variable method. In this study, acetabular posterior wall fracture was treated with arthroscopic reduction and fixation using cannulated screw. The patient recovered immediately and had a satisfactory outcome. In some case of acetabular fracture could be good indication with additional advantages of joint debridement and loose body removal. So, we report our case with technical note.
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PURPOSE: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. RESULTS: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. CONCLUSIONS: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Terapia Combinada/métodos , Terminación Anticipada de los Ensayos Clínicos , Neoplasias Pulmonares/terapia , Terapia de Protones/métodos , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Órganos en Riesgo/efectos de la radiación , Selección de Paciente , Terapia de Protones/efectos adversos , Traumatismos por Radiación/prevención & control , Dosificación Radioterapéutica , Factores de TiempoRESUMEN
Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy.
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BACKGROUND: To assess the potential benefit of proton therapy (PT) over photon therapy, we compared 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT plans in patients undergoing neoadjuvant chemoradiation for resectable rectal cancer at our institution. METHODS: Eight consecutive patients with resectable (T2-T3) rectal cancers underwent 3DCRT, IMRT, and 3-dimensional conformal PT treatment planning. Initial target volumes (PTV1) were contoured using the Radiation Therapy Oncology Group anorectal atlas guidelines. Boost target volumes (PTV2) consisted of the gross rectal tumor plus a uniform 2-cm expansion. Plans delivered 45 Gray (Gy) or Cobalt Gray Equivalent (CGE) to the PTV1 and a 5.4-Gy (CGE) boost to the PTV2. Ninety-five percent of the PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Standard normal-tissue constraints were utilized. Wilcoxon paired t-tests were performed to compare various dosimetric points between the 3 plans for each patient. RESULTS: All plans met all normal-tissue constraints and were isoeffective in terms of PTV coverage. The proton plans offered significantly reduced median normal-tissue exposure over the 3DCRT and IMRT plans with respect to pelvic bone marrow at the V5Gy, V10Gy, V15Gy, and V20Gy levels and the small bowel space at the V10Gy and V20Gy levels. The proton plans also offered significantly reduced median normal-tissue exposure over the 3DCRT plans with respect to the small bowel at the V30Gy and V40Gy levels and the urinary bladder at the V40Gy level. CONCLUSIONS: By reducing bone marrow exposure, PT may reduce the acute hematologic toxicity of neoadjuvant chemoradiation and increase the likelihood of uninterrupted chemotherapy delivery. Bone marrow sparing may also facilitate the delivery of salvage chemotherapy for patients who subsequently develop hematogenous metastasis. Reduced small bowel exposure using PT may also reduce toxicity and possibly facilitate the use of more-aggressive chemotherapy with radiotherapy.
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BACKGROUND: Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. METHODS: Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. RESULTS: Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. CONCLUSIONS: Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.
RESUMEN
In this case report, we present the history and treatment of a 70-year-old man with synchronous bilateral non-small-cell lung cancers with proton-beam radiation. Surgical treatment was not feasible and optimized photon intensity-modulated radiotherapy (IMRT) to the primary tumors would have resulted in unacceptably high normal-tissue exposures. Proton-beam radiation enabled radiation dose escalation and concurrent chemotherapy while maintaining normal-tissue tolerance.
RESUMEN
Desmoid tumors are benign mesenchymal tumors with a strong tendency for local recurrence after surgery. Radiotherapy improves local control following incomplete resection, but nearby organs at risk may limit the dose to the target volume. The patient in this report presented with a recurrent desmoid tumor of the right flank and underwent surgery with microscopically positive margins. Particular problems presented in this case included that the tumor bed was situated in close proximity to the liver and the right kidney and that the right kidney was responsible for 65% of the patient's renal function. Intensity-modulated radiation therapy plans delivering 54 Gy necessarily exposed the right kidney to a V18 of 98% and the liver to a V30 of 55%. Proton therapy plans significantly reduced the right kidney V18 to 32% and the liver V30 to 28%. In light of this, the proton plan was utilized for treatment of this patient. Proton therapy was tolerated without gastrointestinal discomfort or other complaints. Twenty-four months after initiation of proton therapy, the patient is without clinical or radiographic evidence of disease recurrence. In this setting, the improved dose distribution associated with proton therapy allowed for curative treatment of a patient who arguably could not have been safely treated with intensity-modulated radiation therapy or other methods of conventional radiotherapy.