Corrigendum to "Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis".

[This corrects the article DOI: 10.1155/2020/1385978.].

Treatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.

The first parent-child diagnosis of a multifocal squamous odontogenic tumor: A case report.

Squamous odontogenic tumors (SOT) are rare, benign, odontogenic neoplasms of the jaws. The sporadically reported cases with multifocal SOTs seem to have a marked predilection for younger African American patients. In this case report a 14-year-old Caucasian male presented with swelling of the vestibular alveolar process, slight tooth divergence, and mobility. A multifocal squamous odontogenic tumor was diagnosed and subsequently treated twice with surgical enucleation. Two and a half years earlier his mother was diagnosed and treated for a similar multifocal SOT. Next-Generation-Sequencing targeted resequencing mutational analysis of the maternal surgical specimens was performed. No potential causal mutation could be identified. Postoperative follow-up of the patient showed no recurrence of the SOT after 2 years. This case report substantiates the possibility of a familial relationship in (multifocal) SOT, possibly changing current ideas concerning the etiology and treatment of these neoplasms.

Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare variant of soft tissue sarcoma (STS). Materials and Methods. We reviewed SFT patients (pts) treated at our institution between 12/1990 and 09/2017. RESULTS: We identified 94 pts with a median follow-up (mFU) of 4.7 years (range: 0.1-21.53). Primary sites were the chest (33%), abdomen (21.3%), brain (12.8%), and extremities (9.6%); 6.4% of pts presented with synchronous metastasis. Median overall survival (mOS) from the first diagnosis was 56.0 months (m) (0.3-258.3). Doege-Potter syndrome was seen in 2.1% of pts. Primary resection was performed in 86 pts (91.5%). Median progression-free survival was 34.1 m (1.0-157.1), and 43% of pts stayed SFT-free during FU. Local recurrence occurred in 26.7% after a mFU of 35.5 m (1.0-153.8), associated with an OS of 45.1 m (4.7-118.2). Metachronous metastasis occurred in 30.2% after a mFU of 36.0 m (0.1-157.1). OS in metastatic pts was 19.0 m (0.3-149.0). Systemic therapy was given to 26 pts (27.7%) with inoperable/metastatic disease. The most common (57.7%) upfront therapy was doxorubicin, achieving responses in 13.3% of pts with a PFS of 4.8 m (0.4-23.8). In second line, pts were treated with ifosfamide or pazopanib, the latter achieving the highest response rates. Third-line treatment was heterogeneous. CONCLUSION: SFT is an orphan malignancy with a highly variable clinical course and a considerable risk of local failure and metachronous metastasis. Surgery is the only curative option; palliative systemic therapy is used in inoperable/metastatic cases but achieves low response rates. The highest response rates are seen with pazopanib in second/third line.

Characteristics associated with significantly worse quality of life in mycosis fungoides/Sézary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. AIM: To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. METHODS: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. RESULTS: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (ß = 8·61; P = 0·003) and alopecia (ß = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19-3·89] and emotions (OR 1·88, 95% CI 1·09-3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. CONCLUSIONS: HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients. What's already known about this topic? Cross-sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sézary syndrome (SS) have shown significant impairment in health-related quality of life (HRQoL). Previous studies on assessing gender-specific differences in HRQoL in MF/SS are conflicting. More advanced-stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS. In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema. MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well-being.

Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

Multimodular assessment of a calcified extraradicular deposit on the root surfaces of a mandibular molar.

AIM: To achieve a better understanding of a calcified extraradicular deposit on the apical root surfaces of a mandibular first molar associated with a radicular cyst and a sinus tract. A multimodular approach was applied using a combination of multiple investigation methods. SUMMARY: This case report presents a mandibular first molar with a calcified extraradicular deposit on the apical root surfaces of both roots. An apical periodontitis lesion was present and a sinus tract served as the only communication with the oral cavity. Diagnosis and treatment planning were based on clinical, radiographic (two- and three-dimensional) and ultrasound examination. The tooth was further analysed after extraction using microscopic imaging, nano-computed tomography (nano-CT), hard- and soft tissue histology and electron probe microanalysis. This multimodular approach revealed the calculus-like appearance and mineral composition of the extraradicular deposit. Multiple hypotheses about its aetiology are discussed. KEY LEARNING POINTS: Calcified extraradicular deposits can develop on the apical root surfaces of teeth with apical periodontitis in association with a radicular cyst and sinus tract. A sinus tract can serve as the only communication between the apical lesion and the oral cavity whilst no periodontal defects are present. The interplay of intra-oral radiography, high resolution CBCT, nano-CT, hard tissue histology and EPMA can reveal the calculus-like appearance and composition of the extraradicular deposit. Calcified extraradicular deposits appear hyperechoic on ultrasound imaging and can lead to the occurrence of twinkling artefacts due to their rough mineralized surface.

Understanding external cervical resorption patterns in endodontically treated teeth.

AIM: To understand the patterns of external cervical resorption (ECR) in endodontically treated teeth. To compare characteristics and mechanisms of ECR in root filled teeth with those established in teeth with vital pulps. METHODOLOGY: Seven cases of endodontically treated permanent teeth displaying ECR were investigated. ECR diagnosis was based on clinical findings and radiographic examination with cone-beam computed tomography. The extracted teeth were further analysed by a nano-focus computed tomographic (nano-CT) system, hard-tissue histology and scanning electron microscopy (SEM). To make a comparison with teeth with vital pulps, representative cases with ECR were also included. RESULTS: All endodontically treated teeth had a similar ECR pattern. This pattern reflected many similarities to that seen in teeth with vital pulps; that is, three stages were observed namely initiation, resorption and repair. In particular, during the initiation stage (1st stage), the resorption started below the gingival epithelial attachment, at the level of cementum. In the resorption stage (2nd stage), ECR spreads towards the treated pulp space and in a coronal-apical direction, creating multiple resorption channels. The pulp and the pericanalar resorption resistant sheet (PRRS) had been removed during root canal treatment and thus offered no retarding or defence mechanism towards ECR. In the reparative stage (3rd stage), reparative hard-tissue formation occurred at a localized scale. CONCLUSIONS: Similar ECR patterns were observed in all examined teeth. These patterns consisted of an initiation, a resorption and a reparative stage. Some differences were noticed between endodontically treated and teeth with vital pulps, mainly in the resorption and reparative stages. The resorption stage in root filled teeth was more intense than the repair stage, as many clastic cells and abundant granulation tissue were observed in all samples. This is possibly due to the absence of the pulp and protective PRRS layer and/or to the altered chemical composition of the root dentine after root canal treatment. Furthermore, at the repair stage, formation of reparative bonelike tissue took place to a lesser extent in root filled teeth.

Salivary acinic cell carcinoma: reappraisal and update.

Epidemiologic and clinicopathologic features, therapeutic strategies, and prognosis for acinic cell carcinoma of the major and minor salivary glands are critically reviewed. We explore histopathologic, histochemical, electron microscopic and immunohistochemical aspects and discuss histologic grading, histogenesis, animal models, and genetic events. In the context of possible diagnostic difficulties, the relationship to mammary analog secretory carcinoma is probed and a classification is suggested. Areas of controversy or uncertainty, which may benefit from further investigations, are also highlighted.

A novel multimodular methodology to investigate external cervical tooth resorption.

AIM: To introduce a multimodular combination of techniques as a novel minimal invasive approach to investigate efficiently and accurately external cervical resorption (ECR). METHODOLOGY: One case of a central incisor with extensive external cervical resorption was selected to demonstrate the potential of a comparative novel study methodology. ECR diagnosis was based on clinical inspection, digital radiography and cone-beam computed tomography (CBCT). After extraction, the tooth was investigated using microfocus computed tomography (micro-CT), nano-CT and hard tissue histology. These techniques were compared for their accuracy and applicability to highlight their advantages and disadvantages. RESULTS: Nano-CT was more effective than micro-CT and CBCT for detailed ex vivo exploration of ECR. The reparative tissue, pericanalar resorption resistant sheet (PRRS), pulp tissue reactions, resorption channels and their interconnection with the periodontal ligament space were accurately visualized by detailed processing and analysis of the nano-CT data set with Dataviewer and CTAn software. Nano-CT analysis provided better insight in the true extent of the resorption, based on quantitative measurements and 3D visualization of the tooth structure. Nano-CT imaging results were similar to hard tissue histology at the mineralized tissue level. To clarify the dynamic phenomenon of reparative tissue formation and substitution of the resorbed tissues, nano-CT needed to be associated with hard tissue histology. CONCLUSION: Nano-CT is a fast and minimal invasive technique for the ex vivo analysis and understanding of ECR and is complementary with hard tissue histology. A combined approach of clinical and CBCT examination, with nano-CT and histological mapping measurements, can provide an ideal platform for future ECR imaging and exploration studies.

Resolution of diffuse skin and systemic Kaposi's sarcoma in a renal transplant recipient after introduction of everolimus: a case report.

We present a case report of a patient with diffuse skin and systemic Kaposi's sarcoma (KS), 1 year after renal transplantation. A concomitant Pyrenochaeta romeroi granuloma of the right hallux was diagnosed and illustrated an important immunodysfunction in our patient. Four months after reduction in immunosuppression and switch to everolimus, a total regression of the KS was observed. Reduction in the immunosuppression and treatment with terbinafine cleared the P. romeroi infection, while lowering immunosuppression and changing the type of immunosuppressive therapy were important steps in the successful management of the KS. In recent years, evidence of the antitumor effects of everolimus is increasing: total regression of KS in combination with renal function preservation in renal graft recipients is possible with mammalian target of rapamycin (mTOR) inhibitor-based regimens. In addition, with increasing numbers of human immunodeficiency virus-positive transplant recipients, mTOR inhibitors may play a more crucial role in the management of KS.

Elevated carcinoembryonic antigen tumour marker caused by head and neck cancer: a case report and literature study.

Carcinoembryonic antigen is a tumour marker commonly increased in gastrointestinal and pulmonary cancers. We report a case of a 46-year-old man with a mucoepidermoid carcinoma of the base of tongue with an elevated and traceable serum carcinoembryonic antigen level. This antigen proved to be a valuable marker in the treatment follow-up. When a raised carcinoembryonic antigen level is found, salivary gland malignancies should be taken into the differential diagnosis and clinical examination of the head and neck region should not be overlooked.

Association between group 2 innate lymphoid cells enrichment, nasal polyps and allergy in chronic rhinosinusitis.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were shown to be involved in the initiation and coordination of Th2-type immune responses in allergic disease animal models. Recently, ILC2s enrichment was noted in chronic rhinosinusitis (CRS) patients; however, the role of ILC2s in coordinating the Th2 response in CRS remains to be elucidated. Here, we characterize the ILC2 compartment in CRS by investigating the correlations between ILC2s, Th2 cells and Th2 cytokines expression in CRS patients. METHODS: We used flow cytometric analysis of sinonasal mucosal tissues of 29 CRS patients and 5 controls to quantify ILC2s and Th2 cells. Messenger RNA expression levels of IL-5, IL-13, IL-25, IL-33, TSLP and GATA3 were determined using qRT-PCR. RESULTS: ILC2s were significantly enriched in nasal polyps (CRSwNP) patients. Multivariate linear regression showed a significant positive association of ILC2 numbers with CRSwNP and allergic CRS and a negative association with the number of previous endoscopic sinus surgeries. Group 2 innate lymphoid cell numbers significantly correlated with Th2 cell frequencies. Messenger RNA expression levels of IL-5 and IL-13 were increased in CRSwNP compared with controls, while mRNA levels of IL-25 and GATA3 were significantly reduced. CONCLUSIONS: Our results characterize the complex interactions between ILC2s and other Th2 response elements in the context of CRS and suggest that ILC2 enrichment occurs in CRSwNP and in allergic CRS patients.

HPV-related oropharyngeal cancers in Flanders (Belgium): a multicenter study.

INTRODUCTION: Human papilloma virus (HPV) was recently reported to play a major role in oropharyngeal carcinoma. Large geographical differences in the disease prevalence have been described. Until now, no data have been reported for Flanders (Belgium). METHODS: A multicenter cooperative study was undertaken at the radiation-oncology departments of Flemish universities. Tumor blocks from patients diagnosed with oropharyngeal carcinoma between 2000 and 2010 were tested for HPV at a single center. Patients' characteristics, treatments, and follow-up data were recorded from medical files. Age standardized incidence rates of oropharyngeal carcinoma were collected from the Belgian Cancer Registry. RESULTS AND CONCLUSIONS: The incidence of oropharyngeal carcinoma has increased in males and females. Tissues were collected from 264 patients and the HPV status could be defined in 249 of them. The prevalence of HPV(+) oropharyngeal carcinoma was 24.78% (19.93-30.36%). In our cohort, HPV(+) tumors occurred in patients with more advanced tumor stages (p < 0.05), who smoked less (p < 0.05), consumed less alcohol (p < 0.05), had a tonsillar/base of tongue sublocalization (p < 0.05), and were older (p < 0.05). After radiotherapy, locoregional control and disease free survival were significantly better for patients with HPV(+) status (p < 0.05) in univariate analysis. HPV status remained a strong predictor of better locoregional control after multivariate analysis. We found that concurrent chemotherapy had an equal benefit for locoregional control in both HPV(+) and HPV(-) patients.

IgG4-related skin lesions: case report and review of the literature.

IgG4-related disease (IgG4-RD) is a systemic disease, mostly affecting the pancreas. It presents as accumulation of IgG4-producing plasma cells in various tissues. Other possible affected organs include the lacrimal glands, salivary glands, lungs, kidneys, liver, bile duct, retroperitoneum, breast, aorta, pituitary gland and prostate. A cutaneous presentation has also been described in the literature, and might be the initial presenting feature of IgG4-RD. We describe a 73-year-old white man who presented with two infiltrated, erythematous nodules on his abdomen. The histopathological characteristics were highly suggestive of IgG4-related cutaneous disease. Immunohistochemical stains were positive for IgG4. In the past, the patient's other organs had also been affected by IgG4-RD. Cutaneous presentation of IgG4-RD has been described previously in the literature but only in Asian patients (both East and South Asian). We also provide an overview of previously reported cutaneous manifestations of IgG4-RD.

Medullary thyroid cancer: prognostic factors for survival and recurrence, recommendations for the extent of lymph node dissection and for surgical therapy in recurrent disease.

BACKGROUND: We reviewed our experience with MTC (medullary thyroid cancer), focusing on recurrence and survival, recommendations for the extent of lymph node (LN) dissection and surgery for recurrent disease. METHODS: Of 51 MTC patients treated between 1988 and 2008 at the University Hospitals Leuven, 38 previously untreated patients were analysed. RESULTS: Overall and disease-specific (DSS) five-year survival rates were 75% and 82%. Variables univariately associated with DSS were age, pN, stage, vascular invasion, pre-operative recurrent laryngeal nerve function and last calcitonin level. Recurrence occurred in 10 patients (26%). For recurrence, age was no longer a prognostic factor and post-operative calcitonin, number of positive LN and of positive compartments proved to be prognostic factors. Of 21 clinical NO patients, 2 out of 6 (33%) undergoing a prophylactic central neck dissection (ND) based on per-operative palpatory suspicion proved pN+, and 2 out of 9 patients (22%) undergoing a prophylactic lateral ND were pN+. Five patients surgically treated for recurrence did not achieve long-term normalisation of calcitonin, but remained alive with locoregional control. CONCLUSION: Overall survival and DSS rates are within the range reported in the literature. The results confirm that (1) total thyroidectomy and central compartment dissection is the treatment of choice in the cN0 patients, (2) additional ipsilateral lateral ND is needed for cN+ disease in the ipsilateral lateral compartment, and (3) in the clinically uninvolved contralateral lateral neck, per-operative inspection should serve as a basis for a decision about further ND. Locoregional control and prolonged survival is achieved in surgically treated locoregionally recurrent MTC.

Cyclophosphamide, doxorubicin, and cisplatin in advanced salivary gland cancer.

OBJECTIVES: Advanced salivary gland cancer is a rare disease that comprises different histopathological tumour types; correspondingly, data on palliative systemic treatment are scarce. Combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) has been reported to induce a reasonable response rate, although fewer than 100 cases have been described. We conducted a retrospective review of advanced salivary gland cancer patients treated with CAP. METHODOLOGY: Fifteen consecutive patients with recurrent, locally advanced, or metastatic progressive salivary gland cancer treated with CAP were identified over a five-year period. The mean age at start of treatment was 53.5 years, and the male/female ratio was 11/4. The most common histological subtypes were adenoid cystic carcinoma and adenocarcinoma not otherwise specified (NOS), with the parotid gland as the most frequently affected anatomical site. RESULTS: A response rate of 60% was achieved, with one complete and eight partial responses and six stable diseases according to RECIST criteria. No patient progressed under treatment. An average of 5.4 treatment cycles were administered; median time to progression after ending CAP was 6.6 months, and median overall survival was 15.1 months. Patients with adenocarcinoma NOS appeared to benefit more than patients with adenoid cystic carcinoma, but had a shorter time to progression. Except for neutropenia with neutropenic fever and alopecia, no NCI-CTC grade III or IV toxicity was observed. CONCLUSION: This retrospective study confirms the clinically meaningful efficacy of CAP in advanced adenocarcinomas NOS of the salivary gland in routine practice, with acceptable safety levels.

Clinico-histologic parameters of osteosarcoma patients with late relapse.

Primary high-grade intramedullary osteosarcoma of the extremities is a clinically aggressive bone tumour. There is an ongoing effort to further improve efficacy of neo-adjuvant chemotherapy and reduce chemotoxicity by trying to identify osteosarcoma patients who are at risk of treatment failure as well as to identify those who can do with less chemotherapy. In only 5% of patients, first distant metastasis or local relapse occurs 5 years or more after initial treatment for osteosarcoma. Patients and physicians can therefore easily erroneously consider a patient with osteosarcoma cured if he or she is disease-free for more than 5 years following diagnosis and treatment. To investigate if these rare late relapsing patients are characterised by specific clinico-pathological features, we examined clinical and histological variables of late relapse (first local recurrence or metastasis 5 years or more after initial diagnosis) out of a total of 2,243 patients, with a special interest in the histological osteosarcoma subtype. In total, 33 patients had a documented relapse 5 years or more after diagnosis. Half of the patients had good response (>or=90% necrosis) to pre-operative chemotherapy and the other half a poor response (<90% necrosis) and late relapses seemed to be more frequently proportionately in those who had a good initial response to chemotherapy. The occurrence of late relapse did not appear to be associated with age or gender. Although not statistically significant, there was a trend for patients with a chondroblastic subtype of osteosarcoma, or a location in the tibia or fibula, to have a higher risk for late relapse.

Utilizing regulatory T cells to control alloreactivity.

Effective resetting of the immune system cannot be achieved by non-specific immunosuppression. Instead, novel strategies aim at harnessing the body's natural tolerance mechanisms to rectify an Ag-specific response without disturbing other immune functions. Fine-tuning of the balance between Ag-specific effector and regulatory T (Tr) cells is a promising strategy that requires detailed understanding of the differentiation and expansion pathways of the relevant Tr cell subsets. Here we review recent developments regarding the control of alloreactivity by induction and expansion of Tr cells. T-cell activation in the presence of tolerogenic APC and cytokines leads to the induction of Tr cells, which can mediate tolerance through cytokine-dependent and/or contact-dependent mechanisms. Better understanding of the mechanisms of immune regulation mediated by Tr cells may enable fine-tuning of specific immune responses and pave the way for novel therapeutic approaches.