To assess the interest of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) to evaluate the tumor response after radiotherapy (RT) in anaplastic thyroid cancer (ATC) patients.
92 ...patients were treated for ATC at our institution from 1987 to 2012, out of which 64 (70%) received an aggressive multimodal treatment and 28 (30%) a palliative treatment. In the multimodal treatment group, curative-intended surgery, chemotherapy, and RT were delivered in 35 (55%), 59 (92%), and 56 (88%) patients. The maximum standardized uptake value (SUVmax) was determined in tumor (T), nodes (N) and metastases (M) in each available 18F-FDG PET/CT.
The median follow-up was 3.2years. The 1-year actuarial overall survival (OS) was 18% (median: 5.2months) in the entire population and 27% (median: 7months) in the multimodal treatment group. In the multivariate analysis, RT, surgery, and pre-RT chemotherapy independently predicted for OS, with HRs respectively of 0.1, 0.3, and 0.5. Quantification of FDG uptake with SUVmax was assessable in 26 (40%), 19 (30%), and 25 (39%) of 18F-FDG PET/CT performed initially (prior to any treatment), prior to RT, and after RT, respectively. Mean SUVmax significantly decreased in T (p<0.001), but not in N (p=0.1) and M (p=0.3) during the assessment period, which might be related to the local effect of RT. Comparing pre- and post-RT 18F-FDG PET/CT, the T mean relative SUVmax decrease was lower (23±54%) in the 4 patients that had a local relapse (LR) as compared with others in the 12 others patients (62±33%; p=0.3). A relative SUVmax decrease inferior to 20% significantly predicted for LR (p=0.02).
The prognosis of ATC patients remains dismal despite an aggressive multimodal treatment. Although our results were not significant, 18F-FDG PET/CT could potentially serve as a surrogate marker of treatment response in ATC.
Summary Aim To assess the interest of18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET/CT) to evaluate the tumor response after radiotherapy (RT) in anaplastic thyroid cancer (ATC) ...patients. Methods and Materials 92 patients were treated for ATC at our institution from 1987 to 2012, out of which 64 (70%) received an aggressive multimodal treatment and 28 (30%) a palliative treatment. In the multimodal treatment group, curative-intended surgery, chemotherapy, and RT were delivered in 35 (55%), 59 (92%), and 56 (88%) patients. The maximum standardized uptake value (SUVmax) was determined in tumor (T), nodes (N) and metastases (M) in each available18 F-FDG PET/CT. Results The median follow-up was 3.2 years. The 1-year actuarial overall survival (OS) was 18% (median: 5.2 months) in the entire population and 27% (median: 7 months) in the multimodal treatment group. In the multivariate analysis, RT, surgery, and pre-RT chemotherapy independently predicted for OS, with HRs respectively of 0.1, 0.3, and 0.5. Quantification of FDG uptake with SUVmax was assessable in 26 (40%), 19 (30%), and 25 (39%) of18 F-FDG PET/CT performed initially (prior to any treatment), prior to RT, and after RT, respectively. Mean SUVmax significantly decreased in T ( p < 0.001), but not in N ( p = 0.1) and M ( p = 0.3) during the assessment period, which might be related to the local effect of RT. Comparing pre- and post-RT18 F-FDG PET/CT, the T mean relative SUVmax decrease was lower (23 ± 54%) in the 4 patients that had a local relapse (LR) as compared with others in the 12 others patients (62 ± 33%; p = 0.3). A relative SUVmax decrease inferior to 20% significantly predicted for LR ( p = 0.02). Conclusion The prognosis of ATC patients remains dismal despite an aggressive multimodal treatment. Although our results were not significant,18 F-FDG PET/CT could potentially serve as a surrogate marker of treatment response in ATC.
The cell proliferation rate has been correlated to the response of breast carcinomas to preoperative chemotherapy (CT) and to disease outcome. However, this parameter is not yet used to select which ...tumours should be treated with preoperative CT. Furthermore, there is no consensus in the method used to evaluate cell proliferation. In poor prognosis breast carcinomas (PPBCs) treated by intensive preoperative CT, we compared the predictive value of S phase fraction (SPF), mitotic index (MI) and Ki67. We also evaluated the prognostic significance of the variation of the MI after CT. A series of 55 T2-T4N0N1M0 breast carcinomas were treated with 4 cycles of cyclophosphamide, 5-fluorouracil (5-FU) and doxorubicin. SPF was determined by flow cytometry on pre-therapeutic needle aspiration products. MI and Ki67 were evaluated on pre-therapeutic biopsy samples and on the tumours after CT. Fifteen patients (27%) had a pathological complete response (pCR), whereas 40 (73%) had residual disease. All three proliferative markers were found to have predictive value, but this value was higher for MI than for SPF (
P=0.04) and Ki67 (
P=0.03): the rate of pCR was 50% in cases with MI>17/3.3 mm
2, but was only 7% in cases with MI under this threshold (
P=0.0003). A significant decrease of MI (mean 10.97) was observed after CT (
P=0.001). Furthermore, we observed that even for patients with residual tumour, the variation of MI after CT was a prognostic parameter and overall survival. The sequential analysis of MI in breast cancers treated by preoperative CT thus provides a surrogate for predicting long-term outcome.
A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid ...cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined.
Medullary thyroid carcinoma in children Berdelou, Amandine; Hartl, Dana; Al Ghuzlan, Abir ...
Bulletin du cancer,
2013 Jul-Aug, Letnik:
100, Številka:
7-8
Journal Article
Recenzirano
Medullary thyroid carcinoma (MTC) is rare in children. MTC is almost always inherited and occurs as part of a multiple endocrine neoplasia type 2A and B, due to germline mutation in the RET ...proto-oncogene. MTC in the pediatric population is most often diagnosed in the course of a familial genetic investigation. But when the child is the proband, a de novo mutation is most often founded. The main aim is to treat MTC before extrathyroidal extension occurs because when distant metastases are present, it is rarely curable. Treatment is based on total thyroidectomy with cervical lymph node dissection.
Purpose
Our aim was to evaluate in anaplastic thyroid carcinoma (ATC) patients the value of
18
F-FDG PET/CT compared with total body computed tomography (CT) using intravenous contrast material for ...initial staging, prognostic assessment, therapeutic monitoring and follow-up.
Methods
Twenty consecutive ATC patients underwent PET/CT for initial staging. PET/CT was performed again during follow-up. The gold standard was progression on imaging follow-up (CT or PET/CT) or confirmation with another imaging modality.
Results
A total of 265 lesions in 63 organs were depicted in 18 patients. Thirty-five per cent of involved organs were demonstrated only with PET/CT and one involved organ only with CT. In three patients, the extent of disease was significantly changed with PET/CT that demonstrated unknown metastases. Initial treatment modalities were modified by PET/CT findings in 25% of cases. The volume of FDG uptake (≥300 ml) and the intensity of FDG uptake (SUV
max
≥18) were significant prognostic factors for survival. PET/CT permitted an earlier assessment of tumour response to treatment than CT in 4 of the 11 patients in whom both examinations were performed. After treatment with combined radiotherapy and chemotherapy, only the two patients with a negative control PET/CT had a confirmed complete remission at 14 and 38 months; all eight patients who had persistent FDG uptake during treatment had a clinical recurrence and died.
Conclusion
FDG PET/CT appears to be the reference imaging modality for ATC at initial staging and seems promising in the early evaluation of treatment response and follow-up.
Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET). Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup of NET with few treatment options. ...IFN-alpha efficacy in patients with MPPGLs was evaluated in a single-center retrospective study. Progression-free survival (PFS) was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen patients received peginterferon alfa-2a (90 to 180 μg/week) or interferon alfa-2b (1.5 to 3 million units × 3/week) at our institution between December 2005 and February 2014 as the first (
n
= 7), second (
n
= 3), or subsequent line (
n
= 4) of treatment. Most of the patients had a slowly progressive disease before IFN-alpha initiation. Eight patients were men (57%); the median age was 44. At the beginning of treatment, 12 patients had progressive disease demonstrated by FDG-PET (
n
= 9), MIBG (
n
= 1), or CT scan (
n
= 2). Most of the patients treated (64%) had metastatic disease limited to or predominantly located in the bones. During IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9 patients (range 1–4). Median PFS was 17.2 months (95% CI 12.1–58.3). We observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive diseases. No partial response according to RECIST 1.1 was observed. Symptomatic relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10 symptomatic pts. Most frequent all grade IFN-α-related toxicities were asthenia (
n
= 10), lymphopenia (
n
= 7), thrombopenia (
n
= 6), and anemia (
n
= 5). Median overall survival was 7.5 years (95% CI 4–NR). This study suggests symptomatic response and tumor control effect with interferon-alpha in progressive MPPGLs.
Mitotane (
o
,
p
′DDD) is the most effective treatment of advanced adrenocortical carcinoma (ACC) but its mechanism of action remains unknown. Previous studies suggested that
o
,
p
′DDA may represent ...the active metabolite of mitotane. We aimed at reevaluating the potential role and pharmacological effects of
o
,
p
′DDA. Functional consequences of
o
,
p
′DDA exposure were studied on proliferation, steroidogenesis, and mitochondrial respiratory chain in human H295R and SW13 adrenocortical cells. Mitotane and its metabolites were quantified using high-performance liquid chromatography combined to an ultraviolet detection in these cells treated with
o
,
p
′DDD or
o
,
p
′DDA and in human adrenal tissues. Dose–response curves up to 300 μM showed that, as opposed to
o
,
p
′DDD,
o
,
p
′DDA did not inhibit cell proliferation nor alter respiratory chain complex IV activity, gene expression nor induce mitochondrial biogenesis, oxidative stress, or apoptosis. However, whereas mitotane drastically decreased expression of genes involved in steroidogenesis,
o
,
p
′DDA slightly reduced expression of some steroidogenic enzymes and exerts weak anti-secretory effects only at high doses. While
o
,
p
′DDD concentration was significantly reduced by 40 % in H295R cell supernatants after 48 h incubation,
o
,
p
′DDA levels remained unchanged suggesting that
o
,
p
′DDA was not efficiently transported into the cells.
o
,
p
′DDA was not detected in cell homogenates or supernatants after 48 h exposure to
o
,
p
′DDD, consistent with the absence of
o
,
p
′DDA production in these models. Finally, unlike
o
′
p
′DDD, we found that
o
,
p
′DDA content was undetectable in two ACC and one normal adrenal gland of mitotane-treated patients, suggesting a lack of cellular uptake and in situ production. Our results demonstrate that
o
,
p
′DDD, but not
o
,
p
′DDA, induces functional alterations in adrenal cells.
Mitotane (o,p'DDD) is the most effective treatment of advanced adrenocortical carcinoma (ACC) but its mechanism of action remains unknown. Previous studies suggested that o,p'DDA may represent the ...active metabolite of mitotane. We aimed at reevaluating the potential role and pharmacological effects of o,p'DDA. Functional consequences of o,p'DDA exposure were studied on proliferation, steroidogenesis, and mitochondrial respiratory chain in human H295R and SW13 adrenocortical cells. Mitotane and its metabolites were quantified using high-performance liquid chromatography combined to an ultraviolet detection in these cells treated with o,p'DDD or o,p'DDA and in human adrenal tissues. Dose-response curves up to 300 μM showed that, as opposed to o,p'DDD, o,p'DDA did not inhibit cell proliferation nor alter respiratory chain complex IV activity, gene expression nor induce mitochondrial biogenesis, oxidative stress, or apoptosis. However, whereas mitotane drastically decreased expression of genes involved in steroidogenesis, o,p'DDA slightly reduced expression of some steroidogenic enzymes and exerts weak anti-secretory effects only at high doses. While o,p'DDD concentration was significantly reduced by 40 % in H295R cell supernatants after 48 h incubation, o,p'DDA levels remained unchanged suggesting that o,p'DDA was not efficiently transported into the cells. o,p'DDA was not detected in cell homogenates or supernatants after 48 h exposure to o,p'DDD, consistent with the absence of o,p'DDA production in these models. Finally, unlike o'p'DDD, we found that o,p'DDA content was undetectable in two ACC and one normal adrenal gland of mitotane-treated patients, suggesting a lack of cellular uptake and in situ production. Our results demonstrate that o,p'DDD, but not o,p'DDA, induces functional alterations in adrenal cells.
: Mitotane (o,p'DDD) is the most effective treatment of advanced adrenocortical carcinoma (ACC) but its mechanism of action remains unknown. Previous studies suggested that o,p'DDA may represent the ...active metabolite of mitotane. We aimed at reevaluating the potential role and pharmacological effects of o,p'DDA. Functional consequences of o,p'DDA exposure were studied on proliferation, steroidogenesis, and mitochondrial respiratory chain in human H295R and SW13 adrenocortical cells. Mitotane and its metabolites were quantified using high-performance liquid chromatography combined to an ultraviolet detection in these cells treated with o,p'DDD or o,p'DDA and in human adrenal tissues. Dose-response curves up to 300 μM showed that, as opposed to o,p'DDD, o,p'DDA did not inhibit cell proliferation nor alter respiratory chain complex IV activity, gene expression nor induce mitochondrial biogenesis, oxidative stress, or apoptosis. However, whereas mitotane drastically decreased expression of genes involved in steroidogenesis, o,p'DDA slightly reduced expression of some steroidogenic enzymes and exerts weak anti-secretory effects only at high doses. While o,p'DDD concentration was significantly reduced by 40 % in H295R cell supernatants after 48 h incubation, o,p'DDA levels remained unchanged suggesting that o,p'DDA was not efficiently transported into the cells. o,p'DDA was not detected in cell homogenates or supernatants after 48 h exposure to o,p'DDD, consistent with the absence of o,p'DDA production in these models. Finally, unlike o'p'DDD, we found that o,p'DDA content was undetectable in two ACC and one normal adrenal gland of mitotane-treated patients, suggesting a lack of cellular uptake and in situ production. Our results demonstrate that o,p'DDD, but not o,p'DDA, induces functional alterations in adrenal cells.
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