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Residual Disease (residual + disease)
Kinds of Residual Disease Terms modified by Residual Disease Selected AbstractsCongenital Cholesteatoma: Risk Factors for Residual Disease and Retraction Pockets,A Report on 117 Cases,THE LARYNGOSCOPE, Issue 4 2007Diane S. Lazard MD Abstract Objectives: To define predictors of residuals and retraction pockets (RP) in children operated on for congenital cholesteatoma (CC). Design and Setting: Retrospective review (1996,2005), academic center. Patients: One hundred seventeen patients treated for CC corresponding to modified Derlacki's criteria were included (median age, 6.5 yr). No case of RP at time of diagnosis, with a mean follow-up of 2.5 years after last surgery. Main Outcome Measures: Clinical and surgical data influencing outcome. Multivariate analysis. Results: Two groups were defined after CC removal: group I (12 cases), no second look required and no case of subsequent re-intervention; group II (105 cases), planned second look always performed (mean delay, 12.1 mo), no difference of sex ratio (M/F = 2). Group I patients were younger than in group II (3.3 vs. 5.9 yr, P < .001). All of them had a normal contralateral eardrum and a disclosure of CC by routine examination (vs. 19% in group II, P < .001). In group I, the mass occupied one or two anterior quadrants (41.6% and 58.4%, respectively) versus more than two quadrants in 46.6% in group II. Residuals and RP rates were 41% and 15%, respectively (only in group II). Predictors for residuals were atticotomy (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.3,6.7) and destruction of stapes (OR 4.3, 95% CI 1.7,10.5). Predictors for RP were eustachian tube extension (OR 6.8, 95% CI 1.7,26.8) and nonreconstructed atticotomy (OR 5.9, 95% CI 1.1,30.9). Conclusions: Young children with small CC had no recurrences. Residuals were more frequent in case of atticotomy and stapes destruction. RP occurred especially in cases of eustachian tube extension and if cartilage tympanoplasty was not performed. Tympanic and canal wall reinforcement should be considered in extensive CC. [source] Surgical treatment of recurrent endometrial carcinomaCANCER, Issue 1 2004Elio Campagnutta M.D. Abstract BACKGROUND Surgery does not have a definite role in the treatment of patients with recurrent endometrial carcinoma, except for those with central pelvic recurrences. The authors describe their experience with surgery in patients with abdominal endometrial recurrences. METHODS Between 1988 and 2000, 75 patients with abdominal and pelvic endometrial recurrences underwent secondary rescue surgery. Patients were classified according to the presence or absence of residual tumor after surgery. Therapy after rescue surgery was undertaken at the discretion of the medical oncologist. The progression-free interval and overall survival were defined as the time from secondary rescue surgery to the specific event and were evaluated by the Kaplan,Meier method and the log-rank test. A Cox proportional hazards regression model was used to compare survival with covariates. RESULTS Fifty-six patients (74.7%) underwent optimal debulking. Major surgical complications were observed in 23 patients (30.7%). Only 1 postoperative death was observed, although the mortality rate for surgical complications after the postoperative period was 8%. Patients who underwent optimal debulking had a significantly better cumulative survival rate compared with patients who had residual disease (36% vs. 0% at 60 months; P < 0.05). Residual disease, chemotherapy after rescue surgery, and central pelvis,vagina as the only site of recurrence were associated significantly with survival. CONCLUSIONS The authors found that this approach was very challenging in terms of the procedures involved, the incidence of major surgical complications, and the high mortality rate. It was useful in increasing overall survival, provided that patients were free of macroscopic disease. Careful selection of patients is needed to minimize mortality. Cancer 2004;100:89,96. © 2003 American Cancer Society. [source] MEDULLARY THYROID CARCINOMA: A 20-YEAR EXPERIENCE FROM A CENTRE IN SOUTH INDIAANZ JOURNAL OF SURGERY, Issue 3 2007Philip Finny Background: Management of medullary thyroid carcinoma (MTC) remains controversial despite many advances over the past five decades. We attempt to review the presentation, management and prognosis of MTC at our institution over the last two decades. Methods: We conducted a retrospective review of the records of 40 patients with MTC over a period of 20 years. Results: Ten patients had hereditary MTC and 30 had sporadic MTC. The mean age of presentation was 41 years. Sixty-five per cent of the patients had a definite thyroid swelling and 43% had lymphadenopathy at the time of presentation. Total thyroidectomy with a central neck dissection was carried out in 82.5% of patients. Adjuvant therapy was given in 75% of patients because of extensive/residual disease. Postoperative hypercalcitoninaemia was seen 73% of patients. 131I metaiodobenzylguanidine scanning was carried out in 16 patients with persistent hypercalcitoninaemia; the uptake was positive in 10 and negative in 6, indicating a positivity of 62%. Conclusion: Medullary thyroid carcinoma accounts for 2.5% of thyroid carcinomas. There is a small male preponderance. In our series 131I metaiodobenzylguanidine scan had a better positivity than what has been reported in the published work. Persistent postoperative hypercalcitoninaemia was associated with a poorer prognosis that did not reach statistical significant. [source] Response measurement after intraarterial chemoradiation in advanced head and neck carcinomaCANCER, Issue 8 2006Magnetic resonance imaging, evaluation under general anesthesia? Abstract BACKGROUND The objectives of this prospective trial were to evaluate the diagnostic accuracy and predictive value of magnetic resonance imaging (MRI) and to use MRI evaluation under general anesthesia (EGA) 6 to 8 weeks after chemoradiation to determine local control. METHODS Eighty-two consecutive patients with advanced-stage squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx were treated with selective targeted chemoradiation. All patients who completed treatment and survived had a minimum follow-up of 3 years. MRI and EGA were performed from 6 to 8 weeks after treatment. Posttreatment MRI findings were compared with pretreatment MRI findings and were graded for risk of local recurrence/residual disease on a 4-point scale. The diagnosis of treatment failure was based on tissue biopsies, which were obtained during EGA or later during follow-up. The predictive value of MRI was analyzed by using a Cox proportional hazards model. RESULTS Only 1 patient with MRI Grade 0 or 1 findings (discrete mass < 10 mm; n = 62 patients) had residual disease 6 to 8 weeks after treatment that was detected during EGA. In 5 patients with MRI findings of Grade 2a and 2b (mass > 10 mm; n = 20 patients), residual disease was detected. After 2 years, 23 patients had a local failure (28%). Twelve local failures were found among 62 patients who had MRI findings of Grade 0 and 1. Posttreatment MRI emerged as an independent predictive factor (hazard ratio, 3.0; P = .014) for local control. CONCLUSIONS Posttreatment MRI studies provided predictive information on local control in addition to pretreatment predictors. In patients with focal masses < 10 mm, the combination of response evaluation under general anesthesia and posttreatment MRI from 6 to 8 weeks after chemoradiation hardly provided more information on the local control than posttreatment MRI alone. Cancer 2006. © 2006 American Cancer Society. [source] Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: Evidence for a drug-induced regulatory phenomenon.CYTOMETRY, Issue 3 2010Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group Abstract Background: Changes of antigen expression on residual blast cells of acute lymphoblastic leukemia (ALL) occur during induction treatment. Many markers used for phenotyping and minimal residual disease (MRD) monitoring are affected. Glucocorticoid (GC)-induced expression modulation has been causally suspected, however, subclone selection may also cause the phenomenon. Methods: We investigated this by following the phenotypic evolution of leukemic cells with flow cytometry from diagnosis to four time points during and after GC containing chemotherapy in the 20 (of 360 consecutive) B-cell precursor patients with ALL who had persistent MRD throughout. Results: The early expression changes of CD10 and CD34 were reversible after stop of GC containing chemotherapy. Modulation of CD20 and CD45 occurred mostly during the GC phase, whereas CD11a also changed later on. Blast cells at diagnosis falling into gates designed according to "shifted" phenotypes from follow-up did not form clusters and were frequently less numerous than later on. Conclusions: Our data support the idea that drug-induced modulation rather than selection causes the phenomenon. The good message for MRD assessment is that modulation is transient in at least two (CD10 and CD34) of the five prominent antigens investigated and reverts to initial aberrant patterns after stop of GC therapy, whereas CD20 expression gains new aberrations exploitable for MRD detection. © 2010 Clinical Cytometry Society [source] Four- and five-color flow cytometry analysis of leukocyte differentiation pathways in normal bone marrow: A reference document based on a systematic approach by the GTLLF and GEIL,,CYTOMETRY, Issue 1 2010Christine Arnoulet Abstract Background: The development of multiparameter flow cytometry (FCM) and increasingly sophisticated analysis software has considerably improved the exploration of hematological disorders. These tools have been widely applied in leukaemias, lymphomas, and myelodysplasias, yet with very heterogeneous approaches. Consequently, there is no extensive reference document reporting on the characteristics of normal human bone marrow (BM) in multiparameter FCM. Here, we report a reference analysis procedure using relevant antibody combinations in normal human BM. Methods: A first panel of 23 antibodies, constructed after literature review, was tested in four-color combinations (including CD45 in each) on 30 samples of BM. After evaluation of the data, a second set of 22 antibodies was further applied to another 35 BM samples. All list-modes from the 65 bone marrow samples were reviewed collectively. A systematised protocol for data analysis was established including biparametric representations and color codes for the three major lineages and undifferentiated cells. Results: This strategy has allowed to obtain a reference atlas of relevant patterns of differentiation antigens expression in normal human BM that is available within the European LeukemiaNet. This manuscript describes how this atlas was constructed. Conclusions: Both the strategy and atlas could prove very useful as a reference of normality, for the determination of leukemia-associated immunophenotypic patterns, analysis of myelodysplasia and, ultimately, investigation of minimal residual disease in the BM. © 2009 Clinical Cytometry Society [source] Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: Potential usefulness in minimal residual disease detectionCYTOMETRY, Issue 2 2009Joseph A. DiGiuseppe Abstract Background: The persistence of minimal residual disease (MRD) following therapy is an established prognostic factor in precursor B-cell acute lymphoblastic leukemia (pB-ALL). Detection of MRD in pB-ALL by flow cytometric immunophenotyping requires demonstration of abnormal antigen expression in leukemic B-cell precursors relative to that of normal B-cell precursors. The gene encoding CD49f (integrin ,-6) is one of several whose overexpression in pB-ALL at diagnosis has been associated with the subsequent detection of MRD. However, whether CD49f might be a useful reagent in the immunophenotypic detection of MRD in pB-ALL has not been evaluated. Methods: We evaluated CD49f expression by 4-color flow cytometry in normal B-cell precursors, and in a series of cases of pB-ALL, both at diagnosis and at intervals following the initiation of therapy. Results: In 10 control marrow samples, CD49f was undetectable or extremely dim in all but a minor subset of normal CD19+ B-lineage cells, whereas in 11 of 15 cases (73%) of pB-ALL, CD49f was moderate or bright at diagnosis, and persisted or became brighter after initiation of therapy. MRD detected using CD49f corresponded precisely with that obtained using a standard panel of antibodies, and permitted the detection of leukemic populations comprising as little as 0.02% of cells. Of the four pB-ALL cases in which CD49f was undetectable or dim at diagnosis, MRD was detected in two; in one of these, CD49f expression was substantially increased in the leukemic cells that persisted following initiation of therapy. Conclusions: CD49f is commonly overexpressed in p-B-ALL, and represents a potentially useful marker for the immunophenotypic detection of MRD. © 2008 Clinical Cytometry Society How to cite this article: DiGiuseppe JA, Fuller SG, Borowitz MJ. Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: potential usefulness in minimal residual disease detection. Cytometry Part B 2008. [source] Treatment of Lentigo Maligna with Imiquimod before Staged ExcisionDERMATOLOGIC SURGERY, Issue 2 2008MURRAY A. COTTER MD BACKGROUND Imiquimod 5% cream has demonstrated effectiveness in the treatment of lentigo maligna (LM) in several small studies. None of the studies to date have included posttreatment surgical removal to confirm negative histologic margins. OBJECTIVE The aim of this retrospective analysis was to assess the efficacy of topical imiquimod in LM by circumferentially examining vertically oriented sections from a geometrically designed "picture frame" margin as well as bread-loafed sections of the central portion after staged excisions of imiquimod-treated lesions of LM. METHODS Forty patients with biopsy-confirmed LM were treated five times a week for 3 months with 5% imiquimod cream before staged excision. Tazarotene 0.1% gel was added when no clinical signs of erythema developed with imiquimod alone after 1 month (10 patients). After the course of topical therapy, patients were assessed for clinical and complete histologic clearance after staged excision. RESULTS A total of 33 of 40 patients had a complete clinical response as determined by the absence of remaining clinical lesion on physical examination. Upon histologic review, 30 of 40 patients had no evidence of LM whereas 10 of 40 harbored residual disease. One patient was found to have histologic evidence of invasion after completing the topical protocol. After a mean follow-up of 18 months (range, 12,34 months) and after complete surgical excision of the treatment site, none of the imiquimod-treated patients had evidence of recurrence. CONCLUSIONS Imiquimod appears to be an effective adjunctive treatment for LM but does not qualify as a replacement therapy for surgery. [source] Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-upDISEASES OF THE ESOPHAGUS, Issue 2 2010M. Zemanova SUMMARY Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44,76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5-fluorouracil (5-FU), 200 mg/m2/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty-four patients (41%) were furthermore non-randomly assigned to paclitaxel 200 mg/m2/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4,8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy-eight patients (73%) had surgery and 63 of them were completely resected. Twenty-two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node-negative and esophageal wall-positive residual disease. There were 10 surgery-related deaths, mostly due to pulmonary insufficiency. Twenty-nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow-up of 52 months (range 27,80), median survival of 18.0 months and 1-, 2-, 3- and 5-year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non-hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long-term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non-hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect. [source] Salvage esophagectomy after definitive chemoradiotherapy for synchronous double cancers of the esophagus and head-and-neckDISEASES OF THE ESOPHAGUS, Issue 1 2010R. Yoshida SUMMARY Head-and-neck cancer is frequently associated with esophageal cancer. Because the operative procedures for these synchronous double cancers are too invasive, definitive chemoradiotherapy tends to be applied as an initial treatment. A salvage esophagectomy for either recurrent or residual disease after definitive chemoradiotherapy in patients with such double cancer has never been reported. We reviewed 21 patients with esophageal cancer who underwent a salvage esophagectomy after definitive chemoradiotherapy. Among them, the treatment course of five patients who underwent a salvage esophagectomy for patients with synchronous double cancers of the esophagus and head-and-neck region was analyzed. Because head-and-neck cancer was well controlled after chemoradiotherapy in all five patients, a salvage esophagectomy was indicated for either recurrent or residual esophageal cancer after definitive chemoradiotherapy. Anastomotic leakage developed in four patients; however, no other complications including pulmonary complications were recognized. All of them were discharged to home and three of them are still alive without any recurrence for 20,43 months. A salvage esophagectomy should be considered as a treatment option for either recurrent or residual esophageal cancer with well-controlled head-and-neck cancer after definitive chemoradiotherapy when complete resection of the esophagus is expected. [source] Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Anna Candoni Abstract Introduction:,WT1 overexpression is described in several oncological diseases including acute myeloid leukemia (AML). Quantification of WT1 in bone marrow samples may be useful as a marker of minimal residual disease (MRD) and may predict the relapse of AML after allogeneic hematopoietic stem cell transplant (HSCT). Methods and results:, The quantitative expression of WT1 was measured in 38 AML patients (16 males and 22 females) at diagnosis, at the time of transplant and after the allogeneic HSCT (at precise time points). All cases showed high WT1 expression levels at diagnosis with a mean of 4189 (SD 3325) and a median of 3495 (range 454,13923) copies WT1/104Abl. At transplant, 25 patients (66%) were in complete cytologic remission (CcR) and 13 (34%) had refractory or relapsed AML. Bone marrow samples from patients transplanted in CcR showed significantly lower WT1 expression levels during HSCT compared with the samples from patients with a relapsed or refractory AML (P = 0.004). After HSCT, a rapid decline in WT1 expression levels was observed in all patients who attained or maintained a condition of CcR. Six of 38 patients (13%) relapsed after HSCT and all of them had an increase in WT1 expression at/or before relapse. Five of these six patients died of leukemia and one was successfully reinduced with donor lymphocyte infusion (DLI) + chemotherapy with a rapid reduction of WT1 levels. Besides, we found a complete concordance between WT1 expression levels and other disease markers (when available). Conclusions:, In our experience, there was a complete concordance between WT1 expression levels (measured by quantitative RT-PCR at precise time points) and status of AML before and after allogeneic HSCT. WT1 may be useful as a non-specific leukemia marker for monitoring MRD and as a predictor of AML clinical relapse. Based on these results, cases with increase of WT1 levels after HSCT and without graft vs. host disease may be candidate to discontinuation of immunosuppression and/or DLI therapy. [source] Comprehensive comparison of FISH, RT-PCR, and RQ-PCR for monitoring the BCR-ABL gene after hematopoietic stem cell transplantation in CMLEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2002Yoo-Jin Kim Abstract: The reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with fluorescence in situ hybridization (FISH) and real-time quantitative RT-PCR (RQ-PCR) for minimal residual disease (MRD) monitoring in 266 post-transplant bone marrow samples from 78 patients with chronic myelogenous leukemia (CML). The sensitivities of FISH to BCR-ABL positive samples determined by first-round (1st) RT-PCR, second-round (2nd) RT-PCR, and RQ-PCR were 64.2%, 25.8%, and 20.7%, respectively. The BCR-ABL/ABL ratio by RQ-PCR had a mean of 0.000,13 in the 1st RT-PCR-negative samples and 1.42 in the 1st RT-PCR-positive samples (P<0.001), and means of 0.000,39 and 0.51 in the 2nd RT-PCR-negative and -positive samples (P< 0.001). The mean ratios of BCR-ABL/ABL by RQ-PCR were significantly different in N/N (1st/2nd RT-PCR) or N/P and P/P (P<0.001), but not in N/N and N/P, which showed that the discriminative power of RQ-PCR is confined to the 1st RT-PCR level. In this respect, monitoring of the 1st RT-PCR might be useful for estimating normalized BCR-ABL levels after transplantation. Nested RT-PCR was of limited use, as RQ-PCR quantified the BCR-ABL transcripts in 60 (91%) of 66 samples determined to be negative by 2nd RT-PCR. FISH was significantly correlated with RQ-PCR in FISH-positive samples (n=24, r=0.79, P=0.001). An increase of FISH preceded that of RQ-PCR in a few cases with molecular relapse. By analyzing a large number of samples post-transplant, we found that RQ-PCR might be the most useful assay for MRD monitoring; however, FISH and RT-PCR were found to be useful complementary tools. [source] Hypomethylation of PRAME is responsible for its aberrant overexpression in human malignanciesGENES, CHROMOSOMES AND CANCER, Issue 9 2007Tino Schenk The preferentially expressed antigen of melanoma (PRAME) is expressed at high levels in large fractions of human malignancies, e.g., acute myeloid leukemia. Therefore, PRAME is an important marker for diagnosis of various malignant diseases and a relevant parameter for monitoring minimal residual disease. It is supposed to be involved in tumorigenic processes. Because of these important aspects we investigated its transcriptional regulation in detail. Most relevant was a detailed DNA methylation analysis of the PRAME 5, region by genomic sequencing in correlation with PRAME expression in various human patient samples and cell lines. In combination with DNA-truncation/transfection experiments with respect to DNA methylation, we show that changes in the methylation pattern in defined parts of the regulatory regions of PRAME are sufficient for its upregulation in cells usually not expressing the gene. © 2007 Wiley-Liss, Inc. [source] Use of MLL/GRAF fusion mRNA for measurement of minimal residual disease during chemotherapy in an infant with acute monoblastic leukemia (AML-M5)GENES, CHROMOSOMES AND CANCER, Issue 4 2005Monika Wilda No abstract is available for this article. [source] Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: Is it necessary for all?HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2006FACS, Phillip K. Pellitteri DO Abstract In the absence of large-scale randomized trials evaluating dissection versus observation of the involved neck after neoadjuvant chemoradiotherapy, there is a need to collect data that will either support or ultimately refute a role for planned posttreatment neck dissection. A significant percentage of patients with extensive (N2 or N3) neck disease who demonstrate a complete response to chemoradiation therapy may harbor residual occult metastases, and identification of this subset of patients remains a clinical challenge. Because surgical salvage rates are greatly diminished when occult nodal disease becomes clinically manifest, planned posttreatment neck dissection is advocated but may not be necessary in all patients. The role of positron emission tomography chemoradiotherapy (PET-CT) in this scenario remains unproven but holds promise in being able to identify which patients may be harboring residual disease in the neck after chemoradiotherapy. The implementation of as yet unidentified molecular tumor markers in combination with PET-CT may ultimately prove to be effective in identifying patients who will best benefit from posttherapy neck dissection. Correlation of imaging results and pathologic node status will be important in determining the accuracy and, therefore, the value of this imaging modality for predicting the presence or absence of residual disease. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Adjuvant fractionated high-dose-rate intracavitary brachytherapy after external beam radiotherapy in Tl and T2 nasopharyngeal carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2004Jiade J. Lu MD Abstract Background. The value of high-dose-rate intracavitary brachytherapy (HDRIB) for persistent or recurrent nasopharyngeal carcinoma has been well described; however, the benefit of routine adjuvant fractionated HDRIB following external beam radiation therapy (EBRT) has not been completely determined. The objective of this analysis was to evaluate the outcome of two fractions of adjuvant HDRIB treatment in Tl and T2 nasopharyngeal carcinoma. Methods. Thirty-three consecutive and nonselected patients who had Tl and T2 non-disseminated nasopharyngeal carcinoma were treated according to an IRB approved institutional research protocol between March 1999 and July 2001. By the 1997 AJCC cancer staging classification, 22 patients (67%) had Tl disease and 11 patients (33%) had T2 disease. Seventeen of these patients who had stage I or stage II disease (i.e., NO or Nl) were treated with EBRT followed by two fractions of adjuvant HDRIB (group 1); 16 patients who had stage III or stage IV disease (i.e., N2 or N3) were treated with concurrent cisplatin, EBRT and adjuvant HDRIB and subsequent adjuvant cisplatin and fluorouracil (5-FU) chemotherapy (group 2). EBRT was delivered by daily conventional fractionation to a total dose of 66 Gy to the primary tumor. Nodal disease received 66 Gy if it was less than 3cm in maximum diameter and 70 Gy if larger or there was palpable residual disease after 66 Gy. A total of 10 Gy of HDRIB in 2 equal fractions of 5 Gy spaced 1 week apart was delivered starting 1 week after the completion of EBRT. All patients were assessed for treatment response, local control, survival, and toxicity. Results. The median follow up for all 29 surviving patients is 29 months (range: 17,38 months). One patient died 7 months and one died 18 months after radiation therapy from the effects of distant metastases; two died of unrelated causes. At the time of this analysis, one patient (3%) had persistent local disease and one patient (3%) developed pathologically confirmed local recurrence in the nasopharynx. In addition, one patient (3%) developed recurrence only in a neck node followed by distant metastasis, and two patients (6%) developed distant metastasis without locoregional relapse. The 2-year local control rate at the primary site was 93.6%, and the overall survival and disease-free survival rates were 82% and 74% respectively. All patients experienced some degree of acute and/or late toxicity related to radiation therapy. Ten patients (30%) experienced grade 3 acute and/or late toxicity and six patients (18%) developed grade 4 acute and/or late toxicity. No grade 5 toxicity occurred. No unexpected damage of structures within the HDRIB fields was detected. Conclusions. EBRT supplemented by two fractions of adjuvant HDRIB produced a 93.6% local control rate for Tl and T2 nasopharyngeal cancer at 2 years of follow up, with acceptable rates of acute and late toxicity. Brief adjuvant HDRIB appears to permit dose escalation safely, even in patients who receive chemotherapy concurrently with conventional radiation therapy. This strategy needs to be optimized and then tested in a prospective randomized phase III trial to learn if it can improve outcome. © 2004 Wiley Periodicals, Inc. Head Neck26: 389,395, 2004. [source] Serial positron emission tomography scans following radiation therapy of patients with head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2001Kathryn M. Greven MD Abstract Background A single institution study was undertaken to evaluate the role of positron emission tomography (PET) scans with fluorodeoxyglucose (FDG) prior to radiation and following radiation. Methods Forty-five patients with head and neck cancers were evaluated with FDG-PET scans as well as either CT or MRI prior to treatment with definitive radiation (RT). These same scans were obtained following completion of RT at 1 month (36 patients), 4 months (28 patients), 12 months (19 patients), and 24 months (15 patients). Standard uptake values (SUV) normalized for blood glucose and lean body mass were calculated on the initial and 1-month post-treatment PET scans. Results Fifteen patients are alive without evidence of disease at 24 to 52 months following RT. Initial SUVs were calculated on the primary tumor site and ranged from 2.5 to 28.5. These values did not have any correlation with local control when examined for the entire group, primary site, or T stage. One-month post-RT SUV ranged from 1.8 to 6.24. Of the 36 1-month post-RT PET scans, six were interpreted as positive for residual disease and were confirmed by biopsy. Four of the five scans, which were interpreted as equivocal, were positive on biopsy. Seven of the 25 scans, which were interpreted as negative for tumor, were positive on biopsy. Four-month scans were more accurate for disease with disease noted in 0 of 18 negative scans, 6 of 7 positive scans, and 2 of 3 equivocal scans. Conclusions PET is useful for initial imaging of head and neck cancers. SUV does not appear to be useful for predicting outcome following treatment with RT. One-month post-RT scans were inaccurate for predicting the presence of cancer. Four-month post-RT scans were a better predictor for the presence of cancer. © 2001 John Wiley & Sons, Inc. Head Neck 23: 942,946, 2001. [source] High sensitivity of chemiluminescent methodology for detection of clonal CDR3 sequences in patients with acute lymphoblastic leukemiaHEMATOLOGICAL ONCOLOGY, Issue 2 2004E. Leal Abstract Detection of minimal residual disease (MRD) in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been achieved using several radioactive labelling methodologies; however, limited information exists about the use of chemiluminescent labelling. Although many malignant disorders are related to cytogenetic alterations, there is not a consistent chromosomal translocation that could serve as a tumour marker for the monitoring of MRD. ALL are derived from B-lymphocytes in 80% of cases. In the early stages of their maturation, the immunoglobulin heavy chain genes (IgH) undergo rearrangements among their V, D, and J segments, giving rise to the Complementary Determining Regions (CDR). Among these, CDR3 is considered unique for each lymphocyte and used as a tumour-specific marker in B-ALL patients. In this study, the CDR3 was labelled with digoxigenin and used as a patient-specific probe to test its sensitivity for further detection of MRD. Fourteen pretreatment samples of bone marrow (BM) or peripheral blood (PB) from B-ALL patients were included. Tumour-specific probes were designed from each clonal product by elimination of the consensus sequences. Ten digoxigenin-labelled probes were hybridized with a mixture of their respective clonal DNA and the polyclonal product from a normal healthy donor, in serial dilutions from 1:1 up to 1:107. A sensitivity range of 1:103,1:106 was obtained, with an average of 1:105. Crossed tests performed in four patients, showed right probe specificity in all cases. We propose that the design of allele-specific probes with chemiluminescent labelling, represents a reliable, sure and sensitive alternative methodology for MRD detection in patients with B-cell lymphoproliferative disorders. Copyright © 2004 John Wiley & Sons, Ltd. [source] Hypermethylation of gene promoters in hematological neoplasiaHEMATOLOGICAL ONCOLOGY, Issue 4 2002C. S. Chim Abstract Cancer cells are associated with global hypomethylation but with focal hypermethylation of specific gene promoters organized as CpG island. DNA methyltransferases, DNMT1 and 3 (3a and 3b), have been implicated in mediating maintenance and de novo methylation. Hypermethylation of gene promoters results in the inactivation of the corresponding genes, by preclusion of the formation of the transcription complex, due to the recruitment of MBP, MeCPs and histone deacetylase. This results in the deacetylation of histone and thus a compact chromatin complex unfavourable for the initiation of transcription. This methylation-associated gene silencing has been demonstrated in various genes including tumour suppressor genes (p15, p16, p73, VHL). Therefore, gene promoter hypermethylation collaborates with other mechanisms of gene inactivation such as deletion and intragenic mutations to fulfil Knudson's hypothesis. Hypermethylation may serve as a molecular disease marker for the detection of minimal residual disease. Emerging evidence suggests a possible prognostic value of gene promoter hypermethylation. Moreover, gene hypermethylation may also serve as a target for therapeutic invention by hypomethylating agents. Copyright © 2002 John Wiley & Sons, Ltd. [source] Cd8+/v,5.1+ large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin.HEMATOLOGICAL ONCOLOGY, Issue 2 2002E. Granjo Abstract We report a case of CD8+/V,5.1+ T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3+/TCR,,+/CD8+bright/CD11c+/CD57,/CD56, large granular lymphocytes with expression of the TCR-V,5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR ,-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V, monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease. Copyright © 2002 John Wiley & Sons, Ltd. [source] Prognostic value of p27kip1 expression in adenocarcinoma of the pancreatic head regionHPB, Issue 3 2006Jerzy Mielko Abstract Background. p27kip1 is a tumour suppressor gene, functioning as a cyclin-dependent kinase inhibitor, and an independent prognostic factor in breast, colon, and prostate adenocarcinomas. Conflicting data are reported for adenocarcinoma of the pancreas. The aim of this study was to establish the prognostic value of p27kip1 expression in adenocarcinoma of the pancreatic head region. Patients and methods. The study included 45 patients (male/female ratio 2:1; mean age 59, range 38,82 years) with adenocarcinomas of the pancreatic head region: 24 , pancreatic head, 18 , periampullary and 3 , uncinate process. The patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus-preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1). Eight patients received adjuvant chemotherapy postoperatively. Follow-up time ranged from 3 to 60 months. Tumours were staged according to the pTNM classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded blocks from tumour sections. Quantitative determination of p27kip1 expression was based on the proportion of p27kip1 -positive cells (< 5%= negative). Survival analysis was carried out using the Kaplan-Meier method and Cox regression model. Results. Positive p27kip1 expression was detected in 22 tumours (49%), whereas 23 tumours (51%) were p27kip1 -negative. There were no significant correlations between p27kip1 index and stage or lymph node involvement. Median survival time in patients with p27kip1 -positive tumours was 19 months, whereas in patients with p27kip1 -negative tumours it was 18 months (p=0.53). A significant relationship was found between p27kip1 -negative tumours and radical resection (p=0.04). Multivariate survival analysis revealed that the localization of the tumour (pancreatic head/uncinate process vs periampullary) was the only significant and independent prognosticator (p=0.01, Cox regression model). Resection margins involvement and grade remained nearly significant prognostic factors (p=0.07 and p=0.09, respectively). Conclusion. We conclude that p27kip1 has limited overall prognostic utility in resected carcinoma of the pancreatic head region, but its potential role as a marker of residual disease needs to be further assessed. [source] Disseminated bony metastases following incidental gallbladder cancer detected after laparoscopic cholecystectomyHPB, Issue 4 2003F Youssef Background In patients with gallbladder cancer bony metastases are usually a late feature. Case outline A 47-year-old woman presented with a 2-month history of right upper quadrant pain. Ultrasound scan showed gallstones and a thick-walled gallbladder. Laparoscopic cholecystectomy was performed. Histopathology showed poorly differentiated adenocarcinoma infiltrating the muscular layer and vascular invasion. She was referred for further surgery. Staging CT scan of the abdomen showed no local residual disease. However Tc-99 bone scan suggested disseminated bony metastases, which were confirmed by bone trephine biopsy. The cancer progressed rapidly and the patient died 4 months after the diagnosis. Discussion Bone metastases can occur with early gallbladder cancer and a radioisotope bone scan can avoid unnecessary extensive liver surgery. [source] Various components of the insulin-like growth factor system in tumor tissue, cerebrospinal fluid and peripheral blood of pediatric medulloblastoma and ependymoma patientsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Judith M. de Bont Abstract The insulin-like growth factor (IGF) system plays an important role in neuronal development and may contribute to the development of brain tumors. In this study, we studied mRNA expression levels of IGFs, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor receptors (IGFRs) in 27 pediatric medulloblastomas, 13 pediatric ependymomas and 5 control cerebella. Compared to normal cerebellum, mRNA levels of IGFBP-2 and IGFBP-3 were significantly increased in medulloblastomas and ependymomas. IGFBP-2 expression was indicative of poor prognosis in medulloblastomas, whereas IGFBP-3 mRNA levels were especially high in anaplastic ependymomas. IGFBP-5 and IGF-II mRNA levels were significantly increased in ependymomas compared to control cerebellum. Protein expression levels of IGFs and IGFBPs were analyzed in the cerebrospinal fluid (CSF) of 16 medulloblastoma, 4 ependymoma and 23 control patients by radioimmuno assay to determine whether they could be used as markers for residual disease after surgery. No aberrant CSF protein expression levels were found for ependymoma patients. In medulloblastoma patients, the IGFBP-3 protein levels were significantly higher than in ependymoma patients and controls. Moreover, enhanced levels of proteolytic fragments of IGFBP-3 were found in the CSF of medulloblastoma patients, being in concordance with a significantly increased IGFBP-3 proteolytic activity in the CSF of these patients. In conclusion, our data suggest that the IGF system is of importance in pediatric medulloblastomas and ependymomas. Larger studies should be conducted to validate the predictive values of the levels of intact IGFBP-3 and proteolytic fragments in CSF in the follow-up of medulloblastomas. © 2008 Wiley-Liss, Inc. [source] Molecular genetic analysis of haematological malignancies: I. Acute leukaemias and myeloproliferative disordersINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2005A. J. BENCH Summary Molecular genetic techniques are now routinely applied to haematological malignancies within a clinical laboratory setting. The detection of genetic rearrangements not only assists with diagnosis and treatment decisions, but also adds important prognostic information. In addition, genetic rearrangements associated with leukaemia can be used as molecular markers allowing the detection of low levels of residual disease. This review will concentrate on the application of molecular genetic techniques to the acute leukaemias and myeloprolferative disorders. [source] Radical radiotherapy with high-dose-rate brachytherapy for uterine cervix cancer long-term results,JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 6 2007TH Khor Summary The aim of this is to report the results of radical radiotherapy in carcinoma of the cervix treated by high-dose rate (HDR) intracavitary brachytherapy and external beam radiotherapy (XRT) at a single centre in Singapore. This is a retrospective analysis of 106 consecutive cases with histologically proven cervical cancer, treated by HDR brachytherapy and XRT at the Mount Elizabeth Hospital from 1990 to 1993. External beam radiotherapy to the pelvis was delivered with 6 MV photons, to 45,50.4 Gy in 1.8 Gy fractions. High-dose-rate brachytherapy comprised two to three applications of an intrauterine tandem with paired ovoids, to a median dose of 18 Gy to point ,A', carried out during XRT. All 106 patients completed treatment. Their ages ranged from 32 to 80 years (median 57 years). Most patients presented with stage II or III disease (44 and 37%, respectively) and with squamous cell carcinoma (91%). Median follow-up time was 59 months (range 2,169 months). The 5-year relapse-free survival rate across all stages was 71%. The corresponding overall survival rate was 69%. Local control was achieved in 86 patients (81%); six patients had residual disease (6%), and 14 patients had local recurrence (13%). Fourteen patients developed metastatic disease (13%). On univariate analysis, tumour stage, haemoglobin level, number of brachytherapy treatments and overall treatment time were found to be prognostic factors for overall survival. Late complications were mild (Radiation Therapy Oncology Group score 1,2), except for one patient with grade 4 rectal toxicity. The complication rates were 8, 14 and 45%, respectively, for the rectum, bladder and vagina (stenosis). The use of two to three fractions of HDR intracavitary brachytherapy in addition to pelvic XRT achieves good outcomes. [source] Outcomes of re-excision after unplanned excisions of soft-tissue sarcomasJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2005Mark W. Manoso MD Abstract Background and Objectives Unplanned excisions of soft-tissue sarcomas of the extremities occur commonly. Our goal was to evaluate the presence of residual disease, the treatment outcomes as they relate to local and distant recurrence and 5-year survival, and the limb functional outcomes in patients with unplanned sarcoma excision who were treated with re-excision and adjuvant therapy. Methods Between 1993 and 1999, 42 patients presented to our institution after unplanned excision of soft-tissue sarcomas. Of those 42 patients, 38 without gross residual disease or metastatic lesions formed the basis of this review. All 38 patients underwent revision wide excision; most (31) also received adjuvant therapy (radiation and/or chemotherapy). Clinical data were obtained from analysis of patient records and radiographic studies. Univariate analysis was performed with logistical regression, and multivariate analysis was performed with Cox modeling. Results The overall 5-year survival rate was 91.3% and the disease-free 5-year survival rate was 82.2%. Univariate analysis showed that stage-III disease (American Joint Committee on Cancer classification of soft-tissue sarcomas), lesions below the fascia, a histologic high-grade, and the development of organ metastasis were statistically significant factors for mortality. Stage-III disease also was significant for mortality on multivariate analysis. Only stage-III disease was significant for the development of local recurrence. Eighty-four percent of the patients had good to excellent functional outcomes. Conclusions Re-excision with adjuvant therapy proved to be a safe and effective method for treating the disease and preserving limb function. J. Surg. Oncol. 2005;91:153,158. © 2005 Wiley-Liss, Inc. [source] The value of monitoring minimal residual disease in the patients with donor lymphocyte infusion as intervention of relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation,AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2010Xiao Ma No abstract is available for this article. [source] A focal lesion in the falx cerebri: Harbinger of classic stage 4 neuroblastoma in an infant cured despite residual disease after minimal therapyPEDIATRIC BLOOD & CANCER, Issue 7 2009Brian H. Kushner MD Abstract An asymptomatic 11 weeks old received no treatment after he was classified as having a suspected atypical form of MYCN -nonamplified hyperdiploid stage 4S neuroblastoma (NB), with masses in an adrenal gland, subcutaneous tissues, and the falx cerebri. Within 2 months, however, disease progressed in dura and bone marrow. Two cycles of low-dose chemotherapy achieved a partial response; treatment was discontinued. Complete remission was documented 24 weeks post-cycle 2, and has continued >6 years. The falx cerebri probably does not represent an atypical site for stage 4S NB, but stage 4 NB with favorable biology is sometimes curable with minimal therapy. Pediatr Blood Cancer 2009; 53:1340,1342. © 2009 Wiley-Liss, Inc. [source] Pre-transplant minimal residual disease in children with acute lymphoblastic leukemiaPEDIATRIC BLOOD & CANCER, Issue 1 2007Parinda A. Mehta MD No abstract is available for this article. [source] Toxicity and efficacy of intensive chemotherapy for children with acute lymphoblastic leukemia (ALL) after first bone marrow or extramedullary relapse,PEDIATRIC BLOOD & CANCER, Issue 5 2004Blythe Thomson MD Abstract Background Approximately 25% of children newly diagnosed with acute lymphoblastic leukemia (ALL) will eventually experience leukemic relapse, with bone marrow being the most common site of recurrence. The ability to achieve a durable second remission is complicated by toxicity and resistant disease. We report a novel combination of chemotherapy for relapsed pediatric ALL. Procedure Thirty pediatric patients with relapsed medullary (n,=,18) and extra-medullary (n,=,12) ALL were enrolled at three pediatric institutions. Following receipt of induction and the first Block A and Block B of intensification, each patient was evaluated for toxicity, efficacy in achieving remission, and long-term survival. Additionally, minimal residual disease (MRD) detection by multidimensional flow cytometry (MDF) was performed. Results During induction, the major non-hematopoeitic toxicities were mucositis (30% of patients) and bacteremia (50% of patients). Two patients (7%) died of toxicity during induction. Toxicity during intensification Block 1A and 1B was markedly reduced. Eight-nine percent of patients with marrow disease achieved a remission following induction and intensification. The event-free survival (EFS) for all patients at 2 and 4 years were 60% (95% CI: 42,78%) and 49% (95% CI: 30,68%), respectively. Conclusions This regimen for patients with relapsed ALL was successful in achieving a second remission for the majority of patients with acceptable toxicity. © 2004 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||