scholarly journals High-sensitive basal serum thyroglobulin 6–12 months after thyroid ablation is strongly associated with early response to therapy and event-free survival in patients with low-to-intermediate risk differentiated thyroid carcinomas

2017 ◽  
Vol 176 (5) ◽  
pp. 497-504 ◽  
Author(s):  
P Trimboli ◽  
V Zilioli ◽  
M Imperiali ◽  
L Ceriani ◽  
L Giovanella
Keyword(s):  
Disease Free Survival ◽  
Roc Curves ◽  
Early Response ◽  
Differentiated Thyroid Carcinoma ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Intermediate Risk ◽  
Serum Thyroglobulin ◽  
Free Survival

Objective High-sensitive thyroglobulin assays (hsTg) has decreased the need for stimulated Tg measurements in patients with differentiated thyroid carcinoma (DTC). However, multiple assays analyzing the same samples may report different values. Accordingly, appropriate assay-specific cut-off levels should be selected in representative patient series. Here, we evaluate the role of a new hsTg assay in low-to-intermediate risk DTC patients and select appropriate assay-specific clinical cut-off limits. Design This was a retrospective study. The response to treatment was assessed according to ATA. Methods Patients with low-to-intermediate risk DTC treated and regularly followed-up in our thyroid center. Tg was measured on the Kryptor Compact Plus Instrument (BRAHMS Thermo Fisher Scientific). Results The study series comprised 201 DTC patients and excellent response (ER) was demonstrated in 184 (91.5%). Optimized threshold of basal Tg (onT4-Tg) measured 6–12 months after initial treatment was set by ROC curves analysis at 0.28 ng/mL. Having onT4-Tg <0.28 ng/mL at 6–12 months after treatment was associated with longer disease-free survival of Kaplan–Meier (P < 0.001), ER at early follow-up (odds ratio (OR): 165, P < 0.001) and absence of relapse during follow-up (OR: 328, P = 0.0001). Conclusions Patients with low- and intermediate-risk DTC could be considered cured when they have onT4-Tg levels <0.28 ng/mL coupled with negative imaging at their first post-ablation visit.

The contribution of epigenetic and genetic changes to predict gastrointestinal stromal tumors (GIST) behavior

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9542-9542 ◽  
Author(s):  
E. Braggio ◽  
D. P. Guimaraes ◽  
C. E. Bacchi ◽  
L. F. Lopes ◽  
I. A. Small ◽  
...  
Keyword(s):  
Risk Group ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Ki 67 ◽  
Kit Mutation ◽  
Free Survival ◽  
P16ink4a Expression ◽  
Disease Free ◽  
E Cadherin

9542 Background: To search for markers for better prognostic evaluation in patients (pts) with GIST was our goal. Loss of E-cadherin expression and/or function by hypermethylation has been correlated with increase in the invasive potential of human tumors. Recently, loss of p16INK4a expression was considered as an independent prognostic factor in pts with GIST. Methods: We investigated the methylation (MT) status for p16Ink4a and E-cadherin by the MT -specific PCR, c-KIT mutation by SSCP-sequencing, p16INK4a and cKIT expressions and KI-67 index by IHC, in 81 pts with completely ressected GIST between Jan 1990 and April 2003. Clinical data and follow-up information were obtained from medical records.A cutoff at 20% and 5% positivity was used for p16INK4a and KI-67, respectively. Univariate analysis of disease-free survival (DFS) and overall survival (OS) were performed by Kaplan Meier method with the log-rank test. Results: Median age was 55 (9–78); Male/female 42/58%; primary tumor sites were stomach (46.9%), small bowell (37.0%), colorectal (8.6%) and peritoneal (6.2%). Median tumor size was 8cm (1.2–35.0). The median follow-up was 24 months. Pts were stratified into low- (24.7%), intermediate- (37.0%) and high- (38.3%) risk pts based on tumor size and mitotic index. There was a significant correlation between risk classification and disease free survival (DFS) (p=0.023) and overall survival (OS) (p=0.010). The p16Ink4a and E-cadherin MT were observed in 19.4% and 63.3% pts, respectively. We observed loss of p16INK4a expression in 64.9% of GISTs. Overall, 78.4% had KIT mutation in exon 11 or 9. There was non-significant correlations between epigenetic alterations, cKIT mutation, p16INK4a expression, KI-67 index and survival. By analysing the three groups separately we found a significant correlation between E-cadherin MT with DFS (p<0.047) only in the intermediate risk group. Conclusion: Our results suggest that E-cadherin MT may be a helpful prognostic factor particularly in the intermediate risk group of GISTs. In contrast with previous results from the literature p16INK4a alterations had no prognostic impact in our samples. No significant financial relationships to disclose.

Pathologic complete response to standard preoperative chemoradiation in patients with locally advanced rectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 686-686
Author(s):  
Madiha Naseem ◽  
Joshua Murray ◽  
Christine E. Simmons ◽  
Nancy Baxter ◽  
Marcus J. Burnstein ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Response To Treatment ◽  
Significant Response ◽  
Free Survival

686 Background: Pathologic complete response (pCR) is associated with lower rates of recurrences and longer disease-free survival rates in locally advanced rectal cancer (LARC) patients. The purpose of this study was to evaluate clinical outcomes of neoadjuvant chemoradiation and pCR among these patients. Methods: A retrospective chart review was performed for all patients treated for LARC between August 2005 and May 2011 at St. Michael's Hospital, Toronto. Patients were stratified into pCR and no-pCR groups and compared with respect to tumor size, nodal status, and treatment characteristics. Descriptive statistics were calculated for all variables of interest. Chi-square and t-tests were conducted to test for associations between categorical and continuous variables respectively. Disease free survival was calculated as the time between diagnosis and recurrence date, censored at last follow up. Results: A total of 92 patient charts were reviewed; 21 patients had metastatic carcinoma and were excluded from analysis. 63.4% (45/71) were male, with a mean age of 61.2 years and median follow up of 15 months. 12.7% (9/71) of patients achieved a pCR, while the remaining 87.35% (62/71) were no-pCR. All pCR patients received and completed standard pre-operative chemotherapy-radiotherapy. 73.4% (52/71) of the patients had complications from chemoradiotherapy. Furthermore, there was a significant association between having a significant response to treatment and achieving a pCR; where 78% (7/9) of pCR patients had a significant response to treatment. Overall, 4/71 patients had a local recurrence, 22.2% (2/9) pCR and 3.2% (2/62) no-pCR. Those with no-pCR had a recurrence at 1 and 2.2 years post diagnosis, while those with pCR had a recurrence at 3.7 years. Conclusions: This study suggests that patients undergoing standard pre-operative chemoradiotherapy are likely to have a significant response and achieve a pCR. Based on this study, although a pCR does not prevent the risk of recurrence, it delays the onset of local recurrence. Longer follow-up is required to determine if these results are robust and to develop future studies to improve efficacy of treatment delivery in LARC patients.

scholarly journals Follow-up of patients with thyroid cancer and antithyroglobulin antibodies: a review for clinicians

2021 ◽  
Author(s):  
Pedro Weslley Rosario ◽  
Marina Carvalho Souza Cortês ◽  
Gabriela Franco Mourão
Keyword(s):  
Total Thyroidectomy ◽  
Differentiated Thyroid Carcinoma ◽  
Initial Therapy ◽  
Response To Therapy ◽  
Initial Assessment ◽  
Serum Thyroglobulin ◽  
Liquid Chromatography Tandem Mass ◽  
Antithyroglobulin Antibodies ◽  
Structural Disease

Antithyroglobulin antibodies (TgAb) are present in up to 25% of patients with differentiated thyroid carcinoma on initial postoperative assessment. Detectable concentrations of TgAb even below the manufacturer’s cut-off can interfere with serum thyroglobulin (Tg) determination. When Tg is quantified using an immunometric assay (IMA) (hereafter referred to as Tg-IMA), this interference results in underestimated values of Tg. Although promising, more clinical trials evaluating the capacity of liquid chromatography/tandem mass spectrometry and of new assays to detect elevated Tg in patients with TgAb and structural disease are necessary, particularly when Tg is undetectable by a second-generation IMA (Tg-2GIMA). Neck ultrasonography (US) should be performed in patients submitted to total thyroidectomy and with negative Tg-IMA but with detectable TgAb more than 6 months after initial therapy. In patients treated with 131I, comparison of TgAb concentrations obtained before this treatment is useful to estimate the risk of disease and to guide the investigation. If initial assessment does not reveal any persistent tumor, repetition of US is recommended while TgAb persist. Significant elevation of TgAb requires extended investigation. On the other hand, patients with negative Tg-IMA and US without abnormalities who exhibit a reduction > 50% in TgAb generally do not require investigation. Although TgAb can interfere with Tg, the management and follow-up of patients submitted to total thyroidectomy with borderline TgAb can probably be the same as those recommended for patients without TgAb if Tg-2GIMA and US indicate an excellent response to therapy. Currently, the presence/absence or the trend of TgAb levels cannot be considered in the follow-up of patients submitted to lobectomy.

Treatment outcomes in pediatric differentiated thyroid carcinoma

2018 ◽  
Vol 31 (10) ◽  
pp. 1117-1122 ◽  
Author(s):  
Nisha Bhavani ◽  
Kingini Bhadran ◽  
Vasantha Nair ◽  
Usha V. Menon ◽  
Praveen V. Pavithran ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Differentiated Thyroid Carcinoma ◽  
Response To Therapy ◽  
American Thyroid Association ◽  
Intermediate Risk ◽  
Cure Rate ◽  
High Risk Disease ◽  
Clinical Records

Abstract Background Until the American Thyroid Association (ATA) guidelines on management of pediatric differentiated thyroid carcinoma (DTC) became available in 2015, all children with DTC were treated like adults. This study aims to investigate the outcome of pediatric DTC and factors predicting the response to therapy in pediatric DTC managed according to adult guidelines. Methods Clinical records of 41 children less than 18 years of age diagnosed with DTC followed from 2007 in a single center were reviewed. According to the new ATA classification for pediatric DTC, five had low-risk, 28 had intermediate-risk and eight had high-risk disease at presentation. Results There was no mortality or recurrence in this cohort of pediatric DTC patients and the cure rate was 46% during a mean follow-up of 44 months when they were managed according to adult guidelines. Neither the new ATA risk classification nor any clinicopathological character was identified which could predict the response to therapy. The new ATA guidelines would have avoided 27% of the radioiodine therapies given. Conclusions This study showed that DTC in children managed according to adult guidelines had a good cure rate. The new ATA guidelines on pediatric DTC might have drastically reduced the number of radioiodine therapies in the affected children. Long term prospective studies are needed to validate the benefits and risks of both these approaches.

scholarly journals Early Response to Dexamethasone as Prognostic Factor: Result from Indonesian Childhood WK-ALL Protocol in Yogyakarta

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Pudjo H. Widjajanto ◽  
Sutaryo Sutaryo ◽  
Ignatius Purwanto ◽  
Peter M. vd Ven ◽  
Anjo J. P. Veerman
Keyword(s):  
Prognostic Factor ◽  
Low Income ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Early Response ◽  
Added Value ◽  
Response To Treatment ◽  
Intrathecal Methotrexate ◽  
Poor Responders ◽  
Free Survival

Early response to treatment has been shown to be an important prognostic factor of childhood acute lymphoblastic leukemia (ALL) patients in Western studies. We studied this factor in the setting of a low-income province in 165 patients treated on Indonesian WK-ALL-2000 protocol between 1999 and 2006. Poor early response, defined as a peripheral lymphoblasts count of ≥1000/μL after 7 days of oral dexamethasone plus one intrathecal methotrexate (MTX), occurred in 19.4% of the patients. Poor responders showed a higher probability of induction failures compared to good responders (53.1% versus 23.3%,P<0.01), higher probability of resistant disease (15.6% versus 4.5%,P=0.02), shorter disease-free survival (P=0.034; 5-year DFS: 24.9% ± 12.1% versus 48.6% ± 5.7%), and shorter event-free survival (P=0.002; 5-year EFS: 9.7% ± 5.3% versus 26.3% ± 3.8%). We observed that the percentage of poor responders in our setting was higher than reported for Western countries with prednisone or prednisolone as the steroids. The study did not demonstrate a significant additive prognostic value of early response over other known risk factors (age and white blood cell count) for DFS and only a moderately added value for EFS.

Impact of T and N Stage and Treatment on Survival and Relapse in Adjuvant Rectal Cancer

2004 ◽  
Vol 22 (10) ◽  
pp. 1785-1796 ◽  
Author(s):  
Leonard L. Gunderson ◽  
Daniel J. Sargent ◽  
Joel E. Tepper ◽  
Norman Wolmark ◽  
Michael J. O'Connell ◽  
...  
Keyword(s):  
High Risk ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Treatment Method ◽  
Intermediate Risk ◽  
Free Survival ◽  
Risk Patients ◽  
N Stage ◽  
Disease Free

Purpose To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies. Patients and Methods Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) ± semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU ± leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%. Results Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P < .001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT. Conclusion Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.

Elevated serum thyroglobulin levels at the time of ablative radioactive iodine therapy indicate a worse prognosis in thyroid cancer: an Australian retrospective cohort study

2016 ◽  
Vol 130 (S4) ◽  
pp. S50-S53 ◽  
Author(s):  
T J Matthews ◽  
E Chua ◽  
A Gargya ◽  
J Clark ◽  
K Gao ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Radioactive Iodine ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Differentiated Thyroid Carcinoma ◽  
Radioactive Iodine Therapy ◽  
Serum Thyroglobulin ◽  
Free Survival ◽  
Thyroglobulin Level ◽  
Well Differentiated

AbstractBackground:Serum thyroglobulin is used as a surrogate marker for well-differentiated thyroid carcinoma recurrence. This study investigates whether thyroglobulin measured at the time of ablative radioactive iodine therapy predicts disease-free survival.Methods:A retrospective review was conducted of patients with well-differentiated thyroid carcinoma presenting from 1989 to 2010 at the Royal Prince Alfred Hospital, New South Wales, Australia. Disease-free survival of patients with a significantly elevated stimulated thyroglobulin level (27.5 µg/l or higher) at the time of ablative radioactive iodine therapy was compared to that of patients without a significantly elevated thyroglobulin level using univariate analysis.Results:Patients with a thyroglobulin level of 27.5 µg/l or higher had an increased relative risk of disease recurrence of 4.50 (95 per cent confidence interval = 1.35–15.04). If lateral neck dissection was required at the time of surgery, patients also had an increased relative risk of macroscopic disease recurrence of 4.94 (95 per cent confidence interval = 1.47–16.55).Conclusion:An elevated thyroglobulin level of 27.5 µg/l or higher at the time of ablative radioactive iodine therapy is a prognostic indicator for macroscopic disease recurrence in well-differentiated thyroid carcinoma.

131J-speichernde pulmonale und ossäre Metastasen differenzierter Schilddrüsenkarzinome bei niedrigem Serum-Thyreoglobulinspiegel – Ausnahme in der Tumornachsorge?

1987 ◽  
Vol 26 (03) ◽  
pp. 139-142 ◽  
Author(s):  
G. Arning ◽  
O. Schober ◽  
H. Hundeshagen ◽  
Ch. Ehrenheim
Keyword(s):  
Serum Level ◽  
Thyroid Carcinoma ◽  
Bone Metastases ◽  
Differentiated Thyroid Carcinoma ◽  
Serum Thyroglobulin ◽  
Thyroglobulin Level ◽  
Low Serum

In the follow-up of differentiated thyroid carcinoma it is discussed whether the tumormarker thyroglobulin can replace the1311 scan, especially when the thyroglobulin serum level is normal. A positive1311 scan of metastases in the follow-up of patients with differentiated thyroid carcinoma combined with a low serum thyroglobulin level is extremely rare. The literature shows a frequency of about 4%. Recently we found 3 cases with a positive1311 scan demonstrating pulmonary and bone metastases whereas the serum thyroglobulin level was low.

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  
Keyword(s):  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Disease Free Survival ◽  
Low Grade ◽  
Survival Times ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

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