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1.
Iowa Orthop J ; 43(2): 45-51, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38213865

ABSTRACT

Background: Wound healing is particularly important for sarcoma patients who undergo neoadjuvant radiation therapy. Previous studies have demonstrated wound complications in this population approaching 35%. With this high rate of wound healing issues, identifying treatment modalities to minimize these complications is of paramount importance. Methods: All patients with high grade bone and soft tissue sarcoma received 15 days of twice daily amino acid supplementation starting in the immediate post-operative period. We documented the healing status of the surgical wound, the primary outcome, at all follow up appointments until six months after surgery. Non-healing wounds were defined as any wound requiring 1) a return visit to the OR for debridement, 2) IV antibiotics (ABX), and 3) unhealed wounds at 6 months post-operatively.1 For each patient, we collected biometrics with lean body mass analysis at preoperative appointment, and two and six weeks postoperatively. The proportion with non-healing wounds was compared with a historical patient cohort using the chi-square test. In a subgroup of participants with body composition measurements, we also compared changes in mean fat mass, lean mass, and psoas index from pre-operative baseline to 6 months post-operative using generalized linear models. Results: A total of 33 consecutive patients were supplemented with a branched chain amino acid (BCAA) formulation. The historical cohort included 146 participants from the previous 7 years (2010-2017). 26% of patients in the historical cohort experienced wound complications compared to 30% in the supplemented group. (p=0.72) When focusing specifically on lower extremity sarcomas treated with neoadjuvant radiation therapy, 46% of patients in the supplemented group experienced wound healing complications compared to 39% in the non-supplemented group (p=0.68). BCAA supplementation was found to be protective with regards to decreasing muscle wasting with no difference in psoas index measurements throughout the study period compared to a 20% muscle loss in the historical cohort (p=0.02). Conclusion: In our limited sample size, there was no difference in wound healing complications between sarcoma patients who received postoperative BCAA supplementation compared to a historical cohort who were not supplemented. Patients who did not receive supplementation had a significant decline in post-operative psoas index following operative sarcoma removal. Level of Evidence: III.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Pilot Projects , Risk Factors , Radiotherapy, Adjuvant/adverse effects , Sarcoma/drug therapy , Sarcoma/surgery , Sarcoma/radiotherapy , Soft Tissue Neoplasms/surgery , Dietary Supplements , Retrospective Studies
2.
PLoS One ; 15(6): e0234419, 2020.
Article in English | MEDLINE | ID: mdl-32511259

ABSTRACT

BACKGROUND AND OBJECTIVES: Sarcomas are commonly managed by surgical resection combined with radiotherapy. Sarcoma treatment is frequently complicated by chronic wounds and late radiation tissue injury (LRTI). This study aims to gain insight in the use and results of hyperbaric oxygen therapy (HBOT) for radiation-induced complications following sarcoma treatment. METHODS: All sarcoma patients treated between 2006 and 2017 in one of the five centers of the Institute for Hyperbaric Oxygen in the Netherlands were included for retrospective analysis. RESULTS: Thirty patients were included, 18 (60.0%) patients were treated for chronic wounds and 12 (40.0%) for LRTI. Two patients with chronic wounds were excluded from analysis as HBOT was discontinued within five sessions. In 11 of 16 (68.8%) patients treated for chronic wounds, improved wound healing was seen. Nine of 12 (75.0%) patients treated for LRTI reported a decline in pain. Reduction of fibrosis was seen in five of eight patients (62.5%) treated for LRTI. CONCLUSIONS: HBOT is safe and beneficial for treating chronic wounds and LRTI in the sarcoma population. Awaiting further prospective results, we recommend referring to HBOT centers more actively in patients experiencing impaired wound healing or symptoms of delayed radiation-induced tissue injury following multimodality sarcoma treatment.


Subject(s)
Hyperbaric Oxygenation , Radiation Injuries/therapy , Sarcoma/radiotherapy , Adult , Aged , Aged, 80 and over , Chronic Disease , Cohort Studies , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Netherlands , Radiation Injuries/etiology , Radiation Injuries/pathology , Retrospective Studies , Sarcoma/surgery , Wound Healing , Young Adult
3.
Brachytherapy ; 19(1): 81-89, 2020.
Article in English | MEDLINE | ID: mdl-31653566

ABSTRACT

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of CT-guided radioactive 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma (HNSTS) after surgery and external beam radiotherapy. METHODS AND MATERIALS: From December 2006 to February 2018, 25 patients with locally recurrent HNSTS after surgery and external beam radiotherapy were enrolled. All the patients successfully underwent CT-guided 125I seed implantation. The primary end points included the objective response rate (ORR) and local progression-free survival (LPFS). The secondary end points were survival (OS) and safety profiles. RESULTS: After 125I seed implantation, the ORR was 76.0%. The 1-, 3-, and 5-year LPFS rates were 65.6%, 34.4%, and 22.9%, respectively, with the median LPFS of 16.0 months. The 1-, 3-, and 5-year OS rates were 70.8%, 46.6%, and 34.0%, respectively, with the median OS of 28.0 months. Furthermore, univariate analyses showed that the recurrent T stage and histological grade were prognostic factors of LPFS, whereas only the histological grade was a predictor of OS. The major adverse events were skin/mucosal toxicities, which were generally of lower grade (≤Grade 2) and were well tolerated. CONCLUSIONS: Radioactive 125I seed implantation could be an effective and safe alternative treatment for locally recurrent HNSTS after failure of surgery and radiotherapy. Recurrent T stage and histological grade were the main factors influencing the efficacy.


Subject(s)
Brachytherapy/methods , Head and Neck Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Salvage Therapy/methods , Sarcoma/radiotherapy , Soft Tissue Neoplasms/radiotherapy , Adult , Brachytherapy/adverse effects , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Iodine Radioisotopes , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Progression-Free Survival , Radiotherapy, Adjuvant , Radiotherapy, Image-Guided/adverse effects , Radiotherapy, Image-Guided/methods , Sarcoma/pathology , Sarcoma/surgery , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/surgery , Survival Rate , Tomography, X-Ray Computed , Young Adult
4.
Semin Pediatr Surg ; 28(6): 150862, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31931970

ABSTRACT

Soft tissue sarcomas of childhood are a heterogenous group of tumors with a wide spectrum of presentations and outcomes. Most patients require multimodal therapy with chemotherapy, surgery and/or radiation. Improved outcomes in recent decades have been achieved through improvements in the comprehensive care of these children through large cooperative group studies, even as little progress has been made in the standard chemotherapy backbone. A thorough understanding of the nuances of surgical therapy for these children is required to minimize both the risk of local failure and the possibility of loss of vital form or function.


Subject(s)
Rhabdomyosarcoma/surgery , Sarcoma/surgery , Soft Tissue Neoplasms/surgery , Child , Humans , Rhabdomyosarcoma/drug therapy , Rhabdomyosarcoma/radiotherapy , Sarcoma/drug therapy , Sarcoma/radiotherapy , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/radiotherapy
5.
Int J Radiat Oncol Biol Phys ; 103(3): 638-645, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30391521

ABSTRACT

PURPOSE: To analyze the efficacy and safety of radioactive I-125 seed implantation in the treatment of recurrent head and neck tumors after radiation therapy. METHODS AND MATERIALS: The data of 101 patients with recurrent head and neck cancer after radiation therapy who received computed tomography guided radioactive I-125 seed implantation were analyzed. The median previous cumulative external irradiation dose was 66 Gy, and the median dose to 90% of the target volume (D90) after operation was 117 Gy. The short-term efficacy was evaluated by Response Evaluation Criteria in Solid Tumors version 1.1, and the adverse event was evaluated by Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The 5-year local control rate was 26.6%, and the 5-year overall survival rate was 15.5%. Univariate analysis showed that factors related to local control rate included age, pathologic type, implantation site, lesion volume, and D90. The 5-year local control rate was 11.5% (2-year) if D90 was <120 Gy and 44.2% if D90 was ≥120 Gy (P = .001). Multivariate analysis showed that pathologic type, lesion volume, and D90 were independent factors related to local control (P = .002, 0, .014, respectively); Karnofsky performance status and lesion volume were independent factors associated with survival (P = .021 and 0, respectively). For the side effects, there were 26 cases of skin or mucosa ulceration (25.7%), 14 cases of pain (13.9%), and 2 cases of dry mouth (2%). The correlation between toxicity and dose had not been found. CONCLUSIONS: Radioactive I-125 seed implantation in the treatment of recurrent head and neck cancer after radiation therapy showed acceptable efficacy and safety. Nonsquamous carcinoma, small lesion volume, and high dose (D90) were correlated with better local control.


Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Iodine Radioisotopes/chemistry , Neoplasm Recurrence, Local , Radiotherapy/methods , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/radiotherapy , Adult , Aged , Aged, 80 and over , Brachytherapy , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/radiotherapy , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Radiotherapy Planning, Computer-Assisted/methods , Retrospective Studies , Sarcoma/diagnostic imaging , Sarcoma/radiotherapy , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
6.
PLoS One ; 13(4): e0195289, 2018.
Article in English | MEDLINE | ID: mdl-29659611

ABSTRACT

PURPOSE: Radio-hyperthermo-chemo (RHC) therapy, which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft tissue tumors has been introduced with the aim of decreasing the possibility of local recurrence after surgery. To avoid unnecessary neoadjuvant therapy and to plan the appropriate surgical treatment, surveillance of RHC therapeutic efficacy during treatment is necessary. In this study, we determined the optimal response criteria to evaluate the efficacy of RHC by comparing preoperative images before and after RHC with pathological evaluation of necrosis in the resected tumor. PATIENTS AND METHODS: From 2004 to 2014, 20 patients were enrolled into this study. Needle biopsy revealed 6 cases of myxoid liposarcoma, 6 cases of undifferentiated pleomorphic sarcoma, 4 cases of myxofibrosarcoma, and 4 cases of synovial sarcoma. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST, we calculated the responses to RHC therapy by comparing pre- and post-RHC therapy images. In addition, resected specimens underwent pathological analysis to evaluate response based on tumor necrosis. The correlation between assessment based on preoperative images and resected tumors were evaluated by the Spearman's rank-order correlation coefficient. RESULT: From the surgical specimens, pathological assessment of necrosis in resected tumor were assessed as less than 50% (2 cases), 50-90% (9 cases), 90-99% (6 cases), and total necrosis (3 cases). Use of the RECIST 1.1 underestimated good responders as stable disease (SD) or progressive disease (PD) in 5 out of 15 cases; on the other hand, use of the modified RECIST did not underestimate the pathological assessment of necrosis. The correlations between responses based on preoperative images and those based on histological assessments were 0.23 (RECIST 1.1) and 0.76 (modified RECIST). CONCLUSION: Because pathological responses can be underestimated using the RECIST 1.1, the modified RECIST, which take into consideration tumor viability, as assessed by contrast MRI, should also be considered when evaluating the efficacy of RHC.


Subject(s)
Hyperthermia, Induced , Preoperative Period , Sarcoma/drug therapy , Sarcoma/radiotherapy , Adult , Combined Modality Therapy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Sarcoma/diagnostic imaging , Sarcoma/surgery , Tomography, X-Ray Computed , Treatment Outcome
7.
Redox Biol ; 14: 417-422, 2018 04.
Article in English | MEDLINE | ID: mdl-29069637

ABSTRACT

Soft tissue sarcomas are a histologically heterogeneous group of rare mesenchymal cancers for which treatment options leading to increased overall survival have not improved in over two decades. The current study shows that pharmacological ascorbate (systemic high dose vitamin C achieving ≥ 20mM plasma levels) is a potentially efficacious and easily integrable addition to current standard of care treatment strategies in preclinical models of fibrosarcoma and liposarcoma both in vitro and in vivo. Furthermore, enhanced ascorbate-mediated toxicity and DNA damage in these sarcoma models were found to be dependent upon H2O2 and intracellular labile iron. Together, these data support the hypothesis that pharmacological ascorbate may represent an easily implementable and non-toxic addition to conventional sarcoma therapies based on taking advantage of fundamental differences in cancer cell oxidative metabolism.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Ascorbic Acid/therapeutic use , Deoxycytidine/analogs & derivatives , Hydrogen Peroxide/metabolism , Iron/metabolism , Radiation-Sensitizing Agents/therapeutic use , Sarcoma/therapy , Animals , Antimetabolites, Antineoplastic/pharmacology , Ascorbic Acid/pharmacology , Cell Line, Tumor , DNA Damage/drug effects , DNA Damage/radiation effects , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Female , Humans , Mice, Nude , Oxidation-Reduction , Radiation-Sensitizing Agents/pharmacology , Sarcoma/drug therapy , Sarcoma/radiotherapy , Gemcitabine
8.
Int J Hyperthermia ; 34(7): 980-987, 2018 11.
Article in English | MEDLINE | ID: mdl-28826283

ABSTRACT

PURPOSE: Radiotherapy before or after resection is one of the pillars of treatment for localised high risk soft tissue sarcomas. Treatment intensification has been described with concurrent chemotherapy and hyperthermia. The aim of this study is to assess local control after multimodal treatment, focussing on the treatment of local recurrences after surgery only. PATIENTS AND METHODS: Of 42 patients treated in a prospective protocol with radiotherapy and hyperthermia, nine were treated for isolated local recurrences without metastatic spread. Most patients were treated with trimodal therapy including chemotherapy with ifosfamide and underwent resection whenever possible. Median follow-up was 1.4 years. RESULTS: The treatment was well tolerated. Estimated disease free survival, distant metastases free survival and local control for the whole cohort after 1.5 years were 66, 73 and 88%, respectively. Neoadjuvant vs. adjuvant treatment influenced local control with a trend to statistical significance. Resection status did not influence local control. The cohort of patients treated for local recurrence after surgery alone had a significantly impaired local control compared to multimodal treatment at primary diagnosis (100 vs. 52%, p < 0.001). CONCLUSIONS: With multimodal therapy including radiotherapy and hyperthermia local tumour control is achievable even in locally recurrent tumours. The clear-cut difference of the treatment of local recurrence in contrast to primary diagnosis might either reflect difficulties in diagnosis and treatment of local recurrences or biological aggressiveness of recurrent tumours. However, we recommend to consider multimodal treatment at primary diagnosis of high risk soft tissue sarcomas.


Subject(s)
Hyperthermia, Induced/methods , Sarcoma/radiotherapy , Sarcoma/therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Sarcoma/pathology , Young Adult
9.
Int J Clin Oncol ; 22(3): 563-568, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28074298

ABSTRACT

BACKGROUND: Current National Comprehensive Cancer Network guidelines for the treatment of retroperitoneal sarcomas (RPS) endorse surgical resection, but the role of radiotherapy (RT) is less clear. We investigate the utilization and benefits of intraoperative RT (IORT) in the treatment of RPS. METHODS: We queried the Surveillance, Epidemiology and End Results (SEER) database (1988-2013) for the utilization of IORT and perioperative external beam RT (EBRT) in patients who underwent surgical resection of RPS. Groups were defined as any IORT (aIORT), IORT alone (IORT-), IORT with EBRT (IORT+) and preoperative and/or postoperative EBRT without IORT (EBRT). Demographics, tumor characteristics, extent of disease, and survival were compared between groups. RESULTS: We identified 908 patients with RPS who underwent surgical resection with perioperative RT. Demographics of age, sex, and race were similar between groups. There was no difference in baseline tumor characteristics of mean size, tumor grade, or histological subtype between groups. A higher percentage of patients receiving aIORT had tumors >20 cm in size, and extension beyond local tissues. Liposarcoma and leiomyosarcoma were the most common subtypes overall and in each subgroup. Patients with liposarcoma undergoing IORT and EBRT (IORT+) demonstrated a survival benefit over both IORT alone (IORT-) and EBRT alone. CONCLUSION: IORT was used infrequently for RPS but generated equivalent outcomes compared to EBRT, despite being utilized more often for larger tumors and those with peri-tumoral soft-tissue invasion. Patients with the most common subtype (liposarcoma) may benefit from combination IORT with adjuvant EBRT versus other regimens.


Subject(s)
Retroperitoneal Neoplasms/radiotherapy , Retroperitoneal Neoplasms/surgery , Sarcoma/radiotherapy , Sarcoma/surgery , Aged , Combined Modality Therapy/statistics & numerical data , Female , Humans , Intraoperative Period , Liposarcoma/mortality , Liposarcoma/pathology , Liposarcoma/radiotherapy , Liposarcoma/surgery , Male , Middle Aged , Postoperative Period , Retroperitoneal Neoplasms/mortality , Retroperitoneal Neoplasms/pathology , SEER Program , Sarcoma/mortality , Sarcoma/pathology , Treatment Outcome
10.
Radiat Oncol ; 11: 65, 2016 Apr 30.
Article in English | MEDLINE | ID: mdl-27138749

ABSTRACT

Here we evaluate the current status of clinical research on regional hyperthermia (RHT) in combination with chemotherapy or radiation therapy in paediatric oncology.Data were identified in searches of MEDLINE, Current Contents, PubMed, and references from relevant articles using medical subject headings including hyperthermia, cancer, paediatric oncology, children, radiation therapy and chemotherapy. Currently, only two RHT centres exist in Europe which treat children. Clinical RHT research in paediatric oncology has as yet been limited to children with sarcomas and germ cell tumours that respond poorly to or recur after chemotherapy. RHT is a safe and effective treatment delivering local thermic effects, which may also stimulate immunological processes via heat-shock protein reactions. RHT is used chiefly in children and adolescents with sarcomas or germ cell tumours located in the abdomino-pelvic region, chest wall or extremities to improve operability or render the tumour operable. It could potentially be combined with radiation therapy in a post-operative R1 setting where more radical surgery is not possible or combined with chemotherapy instead of radiation therapy in cases where the necessary radiation dose is impossible to achieve or would have mutilating consequences. RHT might also be an option for chemotherapy intensification in the neoadjuvant first-line treatment setting for children and adolescents, as was recently reflected in the promising long-term outcome data in adults with high-risk soft tissue sarcomas (EORTC 62961/ESHO trial).The limited data available indicate that combining RHT with chemotherapy is a promising option to treat germ cell tumours and, potentially, sarcomas. RHT may also be beneficial in first-line therapy in children, adolescents and young adults. The research should focus on optimising necessary technical demands and then initiate several clinical trials incorporating RHT into interdisciplinary treatment of children, adolescents and young adults that include translational research components exploring potential immunological mechanisms of action.


Subject(s)
Antineoplastic Agents/therapeutic use , Hyperthermia, Induced/methods , Medical Oncology/methods , Neoplasms/drug therapy , Neoplasms/radiotherapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols , Body Weight , Child , Combined Modality Therapy/methods , Drug Therapy/methods , Fever/therapy , Fibroma/physiopathology , Humans , Neoplasm Recurrence, Local/radiotherapy , Pediatrics/methods , Radiotherapy/methods , Sarcoma/radiotherapy , Young Adult
11.
J Surg Oncol ; 114(1): 65-9, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27111504

ABSTRACT

BACKGROUND/OBJECTIVES: Oligometastatic sarcoma pulmonary metastases (PM) are typically treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) can be an alternative to surgery that can achieve high rates of local control (LC) with limited toxicity. METHODS: Thirty consecutive sarcoma patients received SBRT to 39 PM's from 2011 to 2015 at two university hospitals to a median dose of 50 Gy in 4-5 fractions with CyberKnife or linear accelerator. Patients underwent CT or PET/CT scans q3 months after SBRT. RESULTS: 77% received prior chemotherapy, 70% had 1-3 prior pulmonary resections, and 26% received prior thoracic radiotherapy. Median lesion size was 2.4 cm (range 0.5-8.1 cm). Median follow-up was 16 and 23 months for patients alive at last follow-up. At 12 and 24 months, LC was 94% and 86%, and OS was 76% and 43%. LC and OS did not differ by SBRT technique, fractionation regimen, lesion location, histology, or size (all P > 0.05). Three developed grade 2 chest-wall toxicity with no other grade ≥2 toxicities. CONCLUSIONS: This is the largest series on SBRT for sarcoma PM's and demonstrates that SBRT is well-tolerated with excellent LC across tumor locations and sizes. SBRT should be considered in these patients, and prospective studies are warranted. J. Surg. Oncol. 2016;114:65-69. © 2016 Wiley Periodicals, Inc.


Subject(s)
Lung Neoplasms/radiotherapy , Lung Neoplasms/secondary , Radiosurgery , Sarcoma/radiotherapy , Sarcoma/secondary , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Female , Follow-Up Studies , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Male , Middle Aged , Neoadjuvant Therapy , Positron-Emission Tomography , Radiotherapy, Adjuvant , Sarcoma/diagnostic imaging , Sarcoma/drug therapy , Tomography, X-Ray Computed , Treatment Outcome
12.
J Natl Cancer Inst ; 106(11)2014 Nov.
Article in English | MEDLINE | ID: mdl-25326640

ABSTRACT

Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes.


Subject(s)
Antineoplastic Agents/therapeutic use , Cell Cycle/drug effects , Molecular Targeted Therapy , Sarcoma/drug therapy , Sarcoma/radiotherapy , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab , Cell Survival/drug effects , Chemotherapy, Adjuvant , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Humans , Indazoles , Indoles/therapeutic use , Ipilimumab , Niacinamide/analogs & derivatives , Niacinamide/therapeutic use , Nivolumab , Phenylurea Compounds/therapeutic use , Proto-Oncogene Proteins c-mdm2/drug effects , Proto-Oncogene Proteins c-mdm2/metabolism , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Radiotherapy, Adjuvant , Sarcoma/immunology , Sarcoma/surgery , Signal Transduction/drug effects , Sorafenib , Sulfonamides/therapeutic use , Sunitinib , Tumor Microenvironment/drug effects
13.
Magy Onkol ; 58(1): 65-76, 2014 Mar.
Article in Hungarian | MEDLINE | ID: mdl-24712009

ABSTRACT

Soft tissue sarcomas represent a histopathologically and clinically heterogeneous group of tumors that make up around 1% of malignancies, in which soft tissue sarcomas of the extremities and superficial trunk (STSET) are treated with more or less the same strategy. Over the past 30 years, there has been a migration away from amputation and radical ablative surgical procedures for localized STSET toward more conservative, function-preserving surgery combined with radiotherapy +/- chemotherapy. The latter complex treatment ensures equal local control to radical surgery. This multidisciplinary management includes organ sparing surgery as the main procedure but also radiotherapy of different types applied before, during or after the surgery, chemotherapy depending of the stadium of the tumor and plastic, reconstructive surgery, and last but not least rehabilitation of the patient after treatment. In this publication we overview the practical guidelines for the treatment of STSET based on the available literature from the last decades. Indication and timing of radiotherapy of STSET as well as available external beam and brachytherapy techniques are summarized. The prescribed radiation dose, the role of alternative fractionations, the combination of radiotherapy and systemic chemotherapy, hyperthermia or limb perfusion regards to STSET are also discussed. Practical considerations of radiotherapy, the target volumes and the role of newer radiotherapy technology in STSET treatment are overviewed.


Subject(s)
Extremities , Limb Salvage , Sarcoma/radiotherapy , Sarcoma/surgery , Torso , Brachytherapy , Chemoradiotherapy , Chemotherapy, Cancer, Regional Perfusion , Dose Fractionation, Radiation , Extremities/surgery , Humans , Hyperthermia, Induced , Interdisciplinary Communication , Intraoperative Period , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Adjuvant/methods , Radiotherapy, Computer-Assisted , Randomized Controlled Trials as Topic , Sarcoma/pathology , Torso/surgery , Treatment Outcome
14.
J Surg Oncol ; 109(7): 633-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24464402

ABSTRACT

BACKGROUND: We sought to examine adherence to National Comprehensive Cancer Network guidelines for use of radiation therapy (RT) in patients with soft tissue sarcoma (STS) in the United States. METHODS: The surveillance, epidemiology, and end results cancer registry was queried to identify patients undergoing surgery for truncal and extremity STS from 2004 to 2009. RESULTS: Of 5,075 patients, 50% received RT. Although routine RT is not recommended for Stage I patients, 25% still underwent RT. Even though routine RT is recommended for Stage II and III tumors, only 60% underwent RT. On multivariate analysis predictors of RT included age <50 years (OR 1.57, 95% CI 1.28-1.91), malignant fibrous histiocytoma histology (OR 1.47, 95% CI 1.3-1.92), T2 classification (OR 1.88, 95% CI 1.60-2.20), and G3 (OR 6.27, 95% CI 5.10-7.72). Patients with Stage III STS who received RT showed improved disease specific survival at 5 years compared to those who did not, 68% versus 46%, P <0.001. CONCLUSIONS: Underuse of RT is seen for a significant proportion of patients undergoing treatment for STS in the United States. More effort needs to be directed towards compliance with appropriate treatment recommendations, perhaps by regionalizing sarcoma care or remote multidisciplinary tumor boards.


Subject(s)
Guideline Adherence , Sarcoma/radiotherapy , Adult , Aged , Extremities , Female , Humans , Male , Middle Aged , Neoplasm Staging , SEER Program , Sarcoma/mortality , Sarcoma/pathology , Torso
15.
Eur Rev Med Pharmacol Sci ; 18(24): 3889-97, 2014.
Article in English | MEDLINE | ID: mdl-25555880

ABSTRACT

OBJECTIVE: Cyclophosphamide (CTX) can attack tumour cells, but can also damage the other cells and microstructures of an organism at different levels, such as haematopoietic cells, liver cells, peripheral lymphocyte DNA, and genetic materials. Low dose radiation (LDR) can induce general adaptation reaction. In this study, we explore the effects of low dose radiation on hepatic damage and genetic material damage caused by CTX. MATERIALS AND METHODS: Mice were implanted subcutaneously with S180 cells in the left groin (control group excluded). On days 8 and 11, mice of the LDR and LDR+CTX groups were given 75 mGy of whole-body γ-irradiation; whereas mice of the CTX and LDR+CTX groups were injected intraperitoneally with 3.0 mg of CTX. All mice were sacrificed on day 13. DNA damage of the peripheral lymphocytes, alanine aminotransferase (ALT) activity, total protein (TP), albumin (ALB) of the plasma, malonyl-dialdheyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity of the hepatic homogenate, and micronucleus frequency (MNF) of polychromatoerythrocytes in the bone marrow were analysed. RESULTS: The control group had the lowest MDA content and the highest SOD and GSH-PX activity, whereas the CTX group had the highest MDA content and the lowest SOD and GSH-PX activity. Compared with the CTX group, the MDA content decreased significantly (p < 0.01) and the SOD and GSH-PX activity increased significantly (p < 0.05) in the LDR+CTX group. TP and ALB in control group were higher than that of the other groups. Compared with the sham-irradiated group, TP and ALB in the LDR group elevated significantly (p < 0.05). The control group had the lightest DNA damage, whereas the CTX group had the severest. DNA damage in LDR+CTX group was much lighter compared with that of the CTX group (p < 0.05). MNF in the CTX group increased significantly compared with the control and the sham-irradiated groups (p < 0.01). Compared with the CTX group, MNF in LDR+CTX group had a tendency of decline, but without statistical significance (p > 0.05). CONCLUSIONS: Pre-chemotherapeutic LDR can induce the activities of anti-oxidative enzymes and promote the elimination of free radicles to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose CTX. At the same time, LDR has no obvious effect on the ALT activity of plasma, but may have protective effect on the protein synthesis function of the liver. High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes; however, LDR before chemotherapy may have certain protective effect on DNA damage. Moreover, CTX has potent mutagenic effect; however, LDR may have no protective effect against the genetic toxicity of CTX chemotherapy.


Subject(s)
Cyclophosphamide/toxicity , DNA Damage , Liver Diseases/etiology , Liver/drug effects , Liver/radiation effects , Radiation Injuries, Experimental/etiology , Alanine Transaminase/blood , Animals , Dose-Response Relationship, Radiation , Liver/metabolism , Liver/pathology , Liver Diseases/genetics , Liver Diseases/metabolism , Lymphocytes/drug effects , Lymphocytes/radiation effects , Male , Malondialdehyde/metabolism , Mice , Oxidative Stress/drug effects , Radiation Injuries, Experimental/chemically induced , Radiation Injuries, Experimental/genetics , Sarcoma/drug therapy , Sarcoma/radiotherapy , Superoxide Dismutase/metabolism , Whole-Body Irradiation
16.
Surg Oncol Clin N Am ; 21(2): 201-13, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22365515

ABSTRACT

Historically the surgical management of extremity soft-tissue sarcomas (ESTS) commonly involved amputation. Nowadays limb-sparing, function-preserving surgery is the standard of care for ESTS. Adjuvant therapies such as radiation therapy and chemotherapy are used selectively in an effort to minimize both local recurrence and distant spread. Less common modalities, such as isolated limb perfusion, isolated limb infusion, and hyperthermia are being evaluated to potentially expand the cohort of individuals who may be eligible for limb-sparing surgery and to improve outcomes. This article reviews the standard and evolving approaches to the management of ESTS.


Subject(s)
Amputation, Surgical/methods , Limb Salvage/methods , Salvage Therapy/methods , Sarcoma/surgery , Soft Tissue Neoplasms/surgery , Brachytherapy/methods , Chemotherapy, Cancer, Regional Perfusion/methods , Combined Modality Therapy , Humans , Hyperthermia, Induced/methods , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/prevention & control , Randomized Controlled Trials as Topic , Risk Factors , Sarcoma/drug therapy , Sarcoma/radiotherapy , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/radiotherapy , Treatment Outcome
17.
Chirurg ; 82(11): 995-1000, 2011 Nov.
Article in German | MEDLINE | ID: mdl-22008846

ABSTRACT

The treatment of soft tissue sarcoma is clinically challenging. Referral to an experienced center with an interdisciplinary team is strongly recommended. Neoadjuvant therapy, including irradiation and chemotherapy, has been applied to improve local control rates, eradicate micrometastases and assess chemosensitivity. However, the role of neoadjuvant therapy remains controversial, especially for systemic therapy, as the only available randomized trial failed to prove a benefit for survival. Nevertheless, on the basis of the current body of literature, neoadjuvant therapy can be considered on an individual basis for patients with high-risk tumors. Whenever possible, patients should be included in a clinical trial.


Subject(s)
Neoadjuvant Therapy , Sarcoma/drug therapy , Sarcoma/radiotherapy , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/radiotherapy , Chemotherapy, Cancer, Regional Perfusion , Combined Modality Therapy , Disease-Free Survival , Humans , Hyperthermia, Induced , Prognosis , Randomized Controlled Trials as Topic , Retroperitoneal Neoplasms/drug therapy , Retroperitoneal Neoplasms/mortality , Retroperitoneal Neoplasms/radiotherapy , Retroperitoneal Neoplasms/surgery , Sarcoma/mortality , Sarcoma/surgery , Soft Tissue Neoplasms/mortality , Soft Tissue Neoplasms/surgery
18.
Bull Cancer ; 97(7): 769-78, 2010 Jul.
Article in French | MEDLINE | ID: mdl-20610365

ABSTRACT

Intensity-modulated radiotherapy (IMRT) has highly impacted on the dose delivery thanks to inverse-planning dosimetry. Conformal isodoses to target volumes and critical organ protection have led to treatment possibilities which were unrealizable with conventional 3D technique. Nevertheless, time delivery using IMRT was in some cases longer than 3D radiotherapy. In order to compensate for this limitation, we have developed since 2007 a volumetric modulated arctherapy (RapidArc) in partnership with Varian. The technique, the results of the dosimetry plans, and quality control of the 142 first patients treated since November 2008 are presented in this review.


Subject(s)
Anus Neoplasms/radiotherapy , Genital Neoplasms, Female/radiotherapy , Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Sarcoma/radiotherapy , Algorithms , Cancer Care Facilities , Female , France , Humans , Male , Radiation Injuries/prevention & control , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/instrumentation
19.
Int J Radiat Oncol Biol Phys ; 76(4): 1114-20, 2010 Mar 15.
Article in English | MEDLINE | ID: mdl-19540065

ABSTRACT

PURPOSE: To assess toxicity and outcome following permanent iodine-125 seed implant as an adjunct to surgical resection in cases of advanced thoracic malignancy. METHODS AND MATERIALS: An institutional review board-approved retrospective review was performed. Fifty-nine patients were identified as having undergone thoracic brachytherapy seed implantation between September 1999 and December 2006. Data for patient demographics, tumor details, and morbidity and mortality were recorded. RESULTS: Fifty-nine patients received 64 implants. At a median follow-up of 17 months, 1-year and 2-year Kaplan-Meier rates of estimated overall survival were 94.1% and 82.0%, respectively. The 1-year and 2-year local control rates were 80.1% and 67.4%, respectively. The median time to develop local recurrence was 11 months. Grades 3 and 4 toxicity rates were 12% at 1 year. CONCLUSIONS: This review shows relatively low toxicity for interstitial planar seed implantation after thoracic surgical resection. The high local control results suggest that an incomplete oncologic surgery plus a brachytherapy implant for treating advanced thoracic malignancy merit further investigation.


Subject(s)
Brachytherapy/methods , Iodine Radioisotopes/therapeutic use , Thoracic Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Brachytherapy/adverse effects , Carcinoid Tumor/radiotherapy , Carcinoid Tumor/surgery , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Iodine Radioisotopes/adverse effects , Leiomyosarcoma/radiotherapy , Leiomyosarcoma/surgery , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Male , Mediastinum/surgery , Middle Aged , Neoplasm Recurrence, Local , Neoplasm, Residual , Radiotherapy Dosage , Radiotherapy, Adjuvant/methods , Retrospective Studies , Sarcoma/radiotherapy , Sarcoma/surgery , Thoracic Neoplasms/surgery , Time Factors , Young Adult
20.
Med Phys ; 36(11): 4848-58, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19994492

ABSTRACT

PURPOSE: To establish accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas. METHODS: Protocol patients with advanced extremity sarcomas were treated with external beam radiation therapy and hyperthermia. Invasive temperature measures were compared to noninvasive magnetic resonance thermal imaging (MRTI) at 1.5 T performed during hyperthermia. Volumetric temperature rise images were obtained using the proton resonance frequency shift (PRFS) technique during heating in a 140 MHz miniannular phased array applicator. MRTI temperature changes were compared to invasive measurements of temperature with a multisensor fiber optic probe inside a #15 g catheter in the tumor. Since the PRFS technique is sensitive to drifts in the primary imaging magnetic field, temperature change distributions were corrected automatically during treatment using temperature-stable reference materials to characterize field changes in 3D. The authors analyzed MRT images and compared, in evaluable treatments, MR-derived temperatures to invasive temperatures measured in extremity sarcomas. Small regions of interest (ROIs) were specified near each invasive sensor identified on MR images. Temperature changes in the interstitial sensors were compared to the corresponding ROI PRFS-based temperature changes over the entire treatment and over the steady-state period. Nonevaluable treatments (motion/imaging artifacts, noncorrectable drifts) were not included in the analysis. RESULTS: The mean difference between MRTI and interstitial probe measurements was 0.91 degrees C for the entire heating time and 0.85 degrees C for the time at steady state. These values were obtained from both tumor and normal tissue ROIs. When the analysis is done on just the tumor ROIs, the mean difference for the whole power on time was 0.74 degrees C and during the period of steady state was 0.62 degrees C. CONCLUSIONS: The data show that for evaluable treatments, excellent correlation (deltaT < 1 degrees C) of MRTI-ROI and invasive measurements can be achieved, but that motion and other artifacts are still serious challenges that must be overcome in future work.


Subject(s)
Body Temperature , Hyperthermia, Induced , Magnetic Resonance Imaging , Sarcoma/therapy , Thermography/methods , Catheterization , Combined Modality Therapy , Fiber Optic Technology/methods , Humans , Neoplasm Staging , Protons , Retrospective Studies , Sarcoma/diagnosis , Sarcoma/radiotherapy , Time Factors
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