Rothmund-Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted.

Background: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. Methods: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. Results: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. Conclusions: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD.

Background: To analyze toxicity, patterns of failure, and survival in 106 adult patients with soft tissue sarcomas of the extremity and the superficial trunk treated in a prospective controlled trial of combined Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiotherapy (EBRT). Methods: Patients were treated with surgical resection and 16 Gy or 24 Gy of PHDRB for negative or close/positive margins, respectively. EBRT (45 Gy) was added postoperatively. Adjuvant chemotherapy was given to selected patients with high-grade tumors. Results: The median follow-up was 7.1 years (range, 0.6-16.0). Grade >= 3 adverse events were observed in 22 patients (20.8%), and grade >= 4 events in 14 patients (13.2%). No grade 5 events were noted. Multivariate analysis (p = 0.003) found that Grade >= 3 toxic events increased with increasing implant volume (TV100). Local control, locoregional control, and distant control rates at 5 and 10 years were 89% and 87%, 82% and 80% and 75% and 69%, respectively. Multivariate analysis (p = 0.024) found that positive margins correlated with decreased local control. Disease-free survival and overall survival rates at 5 and 10 years were 64% and 59% and 73% and 62%, respectively. In multivariate analysis, disease-free survival rates decreased with increasing tumor size (p = 0.0001) and inadequate margins (p = 0.024), and overall survival decreased with increasing tumor size (p = 0.001) and male gender (p = 0.039). Conclusions: The combination of conservative surgery, high-dose PHDRB, and EBRT produces adequate function and local control in the majority of patients with soft tissue sarcomas of the extremities and the superficial trunk, including a substantial percentage of cases with positive margins. Patients with larger tumors are at a higher risk of complications, treatment failure, and cancer-related death and require an individualized treatment approach. (C) 2019 Elsevier B.V. All rights reserved.

OBJECTIVE: To evaluate the clinical, radiological and histological factors that can predict local recurrence of fibromatosis. METHODS: A retrospective study was conducted on 51 patients diagnosed with fibromatosis in this hospital from 1983 to 2014. The mean follow-up was 83 months. A study was made of the clinical parameters, location, depth, size, surgical margins, and proliferation index (Ki-67). An evaluation was also made of the risk of recurrence depending on the adjuvant treatment and the relationship between treatment and patient functionality. RESULTS: Tumour location and depth were identified as risk factors for local recurrence, showing statistically significant differences (P<.001 and P=.003, respectively). There were no statistically significant differences in age, gender, size, surgical margins, or adjuvant treatments, or in the Musculoskeletal Tumour Society Score according to the treatment received. The mean Ki-67 was 1.9% (range 1-4), and its value was not associated with the risk of recurrence. DISCUSSION: Deep fibromatosis fascia tumours, and those located in extremities are more aggressive than superficial tumours and those located in trunk. The Ki-67 has no predictive value in local recurrence of fibromatosis. Radiotherapy, chemotherapy, or other adjuvant treatments such as tamoxifen have not been effective in local control of the disease. Given the high recurrence rate, even with adequate margins, a wait and see attitude should be considered in asymptomatic patients and/or stable disease.

Purpose To evaluate the influence of equivalent dose (EQD2) in clinical outcomes of patients with isolated locally recurrent tumors (ILRT), treated with salvage surgery and intra-operative electron beam radiation therapy (IOERT). Methods and materials We retrospectively reviewed 128 patients with non-metastatic ILRT of different tissues (soft tissue sarcomas, head and neck, uterine, and colorectal). Patients had received salvage surgery (R0/R1/R2) and IOERT. Previously not irradiated patients had received additional external beam radiation therapy (EBRT). Results IOERT was delivered at a median dose of 15 Gy (range, 5-25 Gy). Seventy-five patients (60.9%) received additional EBRT of 46 Gy. Median EQD2 of salvage program was 62 Gy and median EQD2 of exclusive IORT was 31.2 Gy. Median follow-up was 19.2 months (range: 1.3-220). Thirty-one patients (24.2%) developed severe (grade 3-5) complications. New locoregional recurrence was documented in 86 (67.2%) of the 123 cases. Five-year rates were 31% for locoregional control, 57% for distant metastasis-free and 31% for overall survival. On multivariate analysis, R0-1 vs. R2 resection (HR 2.2, 95 CI: 1.2-4.1) was statistically significant for locoregional recurrence and EQD2 ¿62 Gy for survival (HR 2.2, 95 CI: 1.1-4.1). Conclusions Surgical radicality (gross macroscopic resection) and radiation dose (EQD2 ¿62 Gy in radiation salvage program) are the dominant prognostic factors beside ILRT histology. Modest rates of long-term disease control are expected when both factors are fulfilled.

PURPOSE: To assess the toxicity and efficacy of salvage wide resection (SWR) with intraoperative electron beam radiation therapy (IOERT) or perioperative high-dose-rate brachytherapy (PHDRB) in previously unirradiated patients (PUP) vs. previously irradiated patients (PIP) with isolated local recurrence of soft tissue sarcomas (STS) of the extremities and the superficial trunk. METHODS AND MATERIALS: PUP received SWR and IOERT/PHDRB with external beam radiation therapy. PIP received SWR and IOERT/PHDRB only. RESULTS: Fifty patients were analyzed retrospectively. PUP (n = 24; 48%) received IOERT (n = 13) or PHDRB (n = 11). PIP (n = 26; 52%) received IOERT (n = 10) or PHDRB (n = 16). Reintervention because of complications was not required in PUP. Nine of 26 (34%) PIP required reintervention (p = 0.01). After a median followup of 3.7 years (range, 0.2-18.3), the 5-year rates of locoregional control, distant control, and overall survival were 54%, 66%, and 56%, respectively. Five-year locoregional control was higher in PUP than in PIP (81% vs. 26%, p = 0.01) and in the extremity locations compared with trunk locations (68% vs. 28%, p = 0.001). Five-year overall survival was superior in unifocal vs. multifocal presentations (70% vs. 36%, p = 0.03) and for tumor sizes <4 vs. >= 4 cm (74% vs. 50%, p = 0.05). CONCLUSIONS: Prior irradiation is the main determinant of locoregional control in patients with isolated local recurrence of STS. The locoregional control rates in PUP were similar to those described in primary STS. In PIP, SWR + IOERT/PHDRB reirradiation yielded modest locoregional control rates and was associated with significant morbidity, especially in PHDRB cases. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

To determine whether the time to loading (TTL) affects locoregional control. METHODS AND MATERIALS: Locoregional control status was determined in 301 patients enrolled in several perioperative high-dose-rate brachytherapy (PHDRB) prospective studies conducted at the University of Navarre. The impact of the time elapsed from catheter implantation to the first PHDRB treatment (TTL) was analyzed. Patients treated with PHDRB alone (n = 113), mainly because of prior irradiation, received 32 Gy in eight twice-a-day treatments or 40 Gy in 10 twice-a-day treatments for negative or close/positive margins, respectively. Patients treated with PHDRB + external beam radiation therapy (EBRT) (n = 188) received 16 Gy in four twice-a-day treatments or 24 Gy in six twice-a-day treatments for negative or close/positive margins followed by 45 Gy of EBRT in 25 treatments. RESULTS: After a median followup of 6.5 years (range, 2-13.6+), 113 patients have failed (37.5%), 65 in the PHDRB-alone group (57.5%) and 48 in the combined PHDRB + EBRT group (25.5%). Patients who started PHDRB before Postoperative Day 5 had a 10-year locoregional control rate of 66.7% and patients who started PHDRB on Postoperative Day 5 or longer had a 10-year locoregional control rate of 51.8% (p = 0.009). Subgroup analysis detected that this difference was only observed in the recurrent cases treated with PHDRB alone (Subset 2; n = 99; p = 0.004). No correlation could be detected between locoregional control rate and TTL in the other patient subsets although a trend toward a decreased locoregional control rate after a longer TTL was observed when they were grouped together (p = 0.089). CONCLUSIONS: Patients should start PHDRB as soon as possible to maximize locoregional control especially in those recurrent cases treated with PHDRB alone. The time effect in other disease scenarios is less clear.

PURPOSE: To develop a simple clinical model predictive of locoregional failure after complete surgical resection followed by perioperative high-dose-rate brachytherapy (PHDRB) and external beam irradiation (EBRT). PATIENT AND METHODS: Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. PHDRB was given to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy of EBRT. RESULTS: After a median followup of 7.4 years (range, 3-12+), 50 patients have failed and 116 remain controlled at last followup. Tumor size, with a cutoff point set at 3cm (p=0.041) and margin status (positive and <1mm vs. negative ¿1mm, p=0.0001) were independent predictors of locoregional control. These two parameters were used to develop a four-tiered, hierarchical scoring system that stratified patients into low-risk (negative ¿1mm margins and size ¿3cm), intermediate-risk (negative ¿1mm margins, and size >3cm), high-risk (positive and <1mm margins and size ¿3cm), and very high-risk categories (positive and <1mm margins and size >3cm). This classification yields 5-year locoregional control rates of 92.3%, 78.0%, 65.5%, and 48.0% for low-, intermediate-, high-, and very high-risk categories, respectively. The predictive ability of the model is highly significant (p=0.0001) with an area under the curve of 0.72 (0.64-0.81). CONCLUSIONS: The risk of locoregional failure after combined surgical resection, PHDRB, and EBRT is mainly determined by the number of residual clonogens, which is inversely proportional to the status of the surgical margins and directly related to the size of the resected tumor. These two parameters generate a four-tiered predictive model that seems to be valid for a number of different common tumors and clinical settings.

Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P = .02) and microscopically involved margin resection status (P = .04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P = .03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy. (C) 2014 Elsevier Inc.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. The presence of metastases and the lack of response to conventional treatment are the major adverse prognostic factors. Therefore, there is an urgent need for new treatment strategies that overcome both of these problems. Our purpose was to elucidate whether the use of the oncolytic adenovirus ¿24-RGD alone or in combination with standard chemotherapy would be effective, in vitro and in vivo, against osteosarcoma. Our results showed that ¿24-RGD exerted a potent antitumor effect against osteosarcoma cell lines that was increased by the addition of cisplatin. ¿24-RGD osteosarcoma treatment resulted in autophagy in vitro that was further enhanced when combined with cisplatin. Of importance, administration of ¿24-RGD and/or cisplatin, in novel orthotopic and two lung metastatic models in vivo resulted in a significant reduction of tumor burden meanwhile maintaining a safe toxicity profile. Together, our data underscore the potential of ¿24-RGD to become a realistic therapeutic option for primary and metastatic pediatric osteosarcoma. Moreover, this study warrants a future clinical trial to evaluate the safety and efficacy of ¿24-RGD for this devastating disease.

PURPOSE: To determine whether perioperative high-dose-rate brachytherapy (PHDRB) implants with larger high-dose regions produce increased locoregional control. METHODS AND MATERIALS: Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. The PHDRB was given to total doses of 16Gy/4 b.i.d. or 24Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy/25 Rx of external beam radiation therapy. The histogram-based generalized equivalent uniform dose (EUD) formulism was used to quantify and standardize the dose-volume histogram into 2-Gy equivalents. The region of interest analyzed included: tissue volume encompassed by the prescription isodose of 4Gy (TV100). Routine dose reporting parameters such as physical dose and single-point 2-Gy equivalent dose were used for reference. RESULTS: After a median followup of 7.4 years (range, 3-12+), 50 patients have failed, and 116 remain controlled at last followup. Overall, EUD was not different in the patients who failed compared with controls (89.1Gy vs. 86.5Gy; p=not significant). When patients were stratified by risk using the University of Navarre Predictive Model, very high-risk patients (i.e., tumors ¿3cm resected with close <1mm/positive margins) had an improved locoregional control with higher EUD values (p=0.028). This effect was not observed in low-, intermediate-, and high-risk University of Navarre Predictive Model categories. CONCLUSIONS: In very high-risk patients, enlarged high-dose regions can produce a dose-response effect. Routine dose reporting methods such as physical dose and single-point 2-Gy equivalent dose may not show this effect, but it can be revealed by histogram-based EUD assessment.

BACKGROUND: The cortactin (CTTN) gene has been found, by transcriptomic profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at 11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of interest as a potential biomarker for osteosarcoma. MATERIALS AND METHODS: Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy, and paired with cell samples from normal tissue, prior to RNA expression analysis on HG-U133A chips (Affymetrix). Semiquantitative CTTN mRNA expression was analyzed by real-time PCR. An osteosarcoma tissue microarray (TMA) containing 233 tissue spots from 48 patients was used for an immunohistochemical (IHC) study of cortactin. RESULTS: Transcriptomic profiling and real-time PCR analysis indicated increased CTTN expression in osteosarcomas (p = 0.001, Student's T test). TMA IHC showed cortactin to be present more frequently and in greater abundance in osteosarcomas than non-tumoral osteoblastic samples (p< 0.006, Mann-Withney test). Analysis of clinical outcomes indicated that overall survival for patients with primary tumors positive for cortactin was significantly lower than that for patients with cortactin negative (or only weakly staining) tumors (p = 0.0278, Log-rank test). CONCLUSIONS: Our preliminary data support the hypothesis that over-expression of cortactin, contained in the 11q13 amplicon, is involved in osteosarcoma carcinogenesis. The potential of cortactin overexpression as a biom

Purpose: The present study was undertaken to determine factors predictive of toxicity, patterns of failure, and survival in 60 adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with combined perioperative high-dose-rate brachytherapy and external beam radiotherapy. Methods and Materials: The patients were treated with surgical resection and perioperative high-dose-rate brachytherapy (16 or 24 Gy) for negative and close/microscopically positive resection margins, respectively. External beam radiotherapy (45 Gy) was added postoperatively to reach a 2-Gy equivalent dose of 62.9 and 72.3 Gy, respectively. Adjuvant chemotherapy with ifosfamide and doxorubicin was given to patients with advanced high-grade tumors. Results: Grade 3 toxic events were observed in 18 patients (30%) and Grade 4 events in 6 patients (10%). No Grade 5 events were observed. A location in the lower limb was significant for Grade 3 or greater toxic events on multivariate analysis (p =.013), and the tissue volume encompassed by the 150% isodose line showed a trend toward statistical significance (p =.086). The local control, locoregional control, and distant control rate at 9 years was 77.4%, 69.5%, and 63.8%, respectively. On multivariate analysis, microscopically involved margins correlated with local control (p =.036) and locoregional control (p =.007) and tumor size correlated with distant metastases (p =.004). The 9-year disease-free survival and overall survival rate was 47.0% and 61.5%, respectively. Multivariate analysis showed poorer disease-free survival rates for patients with tumors >6 cm (p =.005) and microscopically involved margins (p =.043), and overall survival rates decreased with increasing tumor size (p =.011). Conclusions: Grade 3 or greater wound complications can probably be decreased using meticulous treatment planning to decrease the tissue volume encompassed by the 150% isodose line, especially in lower limb locations. Microscopically involved margins remain a predictor of local and locoregional failure, despite radiation doses >70 Gy. Patients with tumors ¿6 cm and microscopically involved margins are at high risk of treatment failure and death from the development of distant metastases.

Objetivo Analizar una larga serie de esta rara entidad para entenderla mejor y valorar el riesgo de malignización y comprender esta enfermedad infrecuente para el correcto diagnóstico y tratamiento. Material y métodos Diecisiete casos de encondromatosis múltiple tratados desde el año 1976 hasta el año 2006. Las variables estudiadas son: edad al diagnóstico y malignización, localización de la lesión, asociación familiar con otros tumores, hallazgos radiológicos, tratamientos aplicados, evolución en el tiempo, metástasis y supervivencia. Resultados Se incluyen 16 casos de Ollier y un caso de síndrome de Maffucci. La gammagrafía fue el método de imagen que nos llevó al diagnóstico. La mediana de edad al diagnóstico de las malignizaciones es de 45 años, mientras que la mediana de edad al diagnóstico de los que no sufrieron malignización fue de 11 años. Fracturas patológicas, dismetr¿¿as y deformidades conducen al diagnóstico en la gente joven. Las lesiones benignas fueron tratadas mediante cirugía menor. Hubo 5 malignizaciones en 4 pacientes (23,5%). El fémur distal y la pelvis son los lugares de mayor frecuencia de malignización, todos ellos hacia condrosarcoma de grado I. La cirugía es el único tratamiento en todos ellos. Conclusiones La enfermedad de Ollier es una enfermedad benigna con alto riesgo de malignización a partir de los 40 años. La gammagrafía ósea es la mejor prueba diagnostica para detectar el crecimiento del tumor y la posible malinización de las múltiples lesiones. La cirugía amplia es la única herramienta para lograr la supervivencia en estos pacientes; por eso el diagnóstico precoz es esencial. Aim To review Ollier disease, an uncommon disease, in order to understand the clinical symptoms, diagnosis, correct treatment, and risk factors in order to prevent malignant transformation. Materials and methods Seventeen cases of Ollier disease were treated between 1976 and 2006. The variables studied included: age at diagnosis and onset of malignant transformation, location of the lesion, family association with other tumours, radiological findings, treatment for the different lesions, metastatic lesions and survival. We excluded patients with Chondrosarcoma without previous diagnosis of Ollier disease. All malignant transformations were assessed by histopathology studies and radiological images. Results We include 16 cases of Ollier's and 1 of Maffucci's syndrome. The median age at diagnosis for patients having malignant transformation was 45 years, whereas the average age at diagnosis for patient without progression to malignancy was 11 years. Pathological fractures, dysmetria and deformities led to the diagnosis in young people. Benign lesions were treated with minor surgery. There were five malignancy transformations in four patients (23.5%), with the distal femur being the most frequent location for transformation to grade I chondrosarcoma. Surgery was the treatment in all of them. We found no family association with other tumours. Conclusions Multiple enchondromatosis is a benign disease with a high risk of malignant transformation above 40 years old. Bone scintigraphy is the best tool for detecting multiple lesions and malignant transformation. Radical surgery is the only way to improve survival, and this is the reason why early diagnosis is essential.

Background: Giant cell tumors (GCT) are relatively rare neoplasms, representing less than 5% of all bone tumors. They are most frequent in the extremities and are characterized by their local aggression. Treatment is typically surgery alone. Localization in the sacrum is rare, and here radiation therapy (RT) may be a useful tool for tumor management because of the difficulty of achieving accurate wide margins of surgical resection. We report a series of four cases treated by intralesional resection and RT. Patients and methods: From 1996 to 2007, four patients with histologically proven sacral giant cell tumors were treated with intentional intralesional surgery and RT in our institution. Three patients were female and one was male. Median age was 35.5 years (range 19-53). Results: After a median follow-up of more than 11 years (range 32-144 months), all the patients are alive and free of disease. Pain and neurological symptoms disappeared after treatment. No severe cases of acute or late toxicity have been reported. No radiological signs of progression were observed. Conclusion: We propose RT be considered as a standard coadjuvant treatment after intralesional surgery for sacral GCT, where efficient local control without severe toxicity is advisable.

Purpose To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods Patients (n = 312) enrolled in several PHDRB prospective Phase I¿II studies conducted at the Clínica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions Two-gray equivalent doses ¿70 Gy may compensate the effect of close margins ¿1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose¿margin interaction is observed in patients treated at lower Eq2Gy doses ¿50 Gy with PHDRB alone.

Infection is one of the most dangerous complications that can be seen when implanting bone or tendon allografts from a deceased donor. The most common germs isolated are found among the cutaneous florae, but sometimes they may be present in the bloodstream as a result of severe injuries suffered before the time of the decease. We present a case of contamination of allografts in a musculoskeletal tissue donor deceased after an accident, whose allografts were contaminated by gastrointestinal microorganisms, probably disseminated through the donor's blood