To determine the performance of intraoperative one-step nucleic acid amplification (OSNA) assay in detecting sentinel lymph node metastases compared to postoperative histology taking into account ...breast cancer molecular classification and to evaluate whether the level of cytokeratin 19 mRNA copy number may be useful in predicting the likelihood of a positive axillary lymph node dissection. OSNA assay was performed in a prospective series of 903 consecutive sentinel lymph nodes from 709 breast cancer patients using 2 alternate slices of each sentinel lymph node. The remaining 2 slices were investigated by histology. Cytokeratin 19 mRNA copy number, which distinguishes negative cases (<250 copies), micrometastases (+, ≥250≤5000 copies) and macrometastases (++, >5000 copies), was compared to axillary lymph node dissection status and to the biological tumor profile. Concordance between OSNA and histopathology was 95%, specificity 95% and sensitivity 93%. Multiple Corresponce Analysis and logistic regression evidenced that positive axillary lymph node dissection was significantly associated with a higher cytokeratin 19 mRNA copy number (>5000; p<0.0001), HER2 subtype (p = 0.007) and lymphovascular invasion (p<0.0001). Conversely, breast cancer patients with cytokeratin 19 mRNA copy number <2000 mostly presented a luminal subtype and a negative axillary lymph node dissection. We confirmed that OSNA assay can provide standardized and reproducible results and that it represents a fast and quantitative tool for intraoperative evaluation of sentinel lymph node. Omission of axillary lymph node dissection could be proposed in patients presenting a sentinel lymph node with a cytokeratin 19 mRNA copy number <2000 and a Luminal tumor phenotype.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity ...and feasibility of high-dose salvage radiation therapy (80 Gy).
Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic (18)F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale.
Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%.
At early follow-up, (18)F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.
Bronchobiliary fistula (BBF) represents a rare but severe complication in patients affected by liver metastases. Although a clinical suspicion can arise when specific clinical signs, in particular ...biliptysis, are present, conventional imaging modalities often fail to confirm the diagnosis. We present a case of a patient affected by colon cancer with liver metastases previously treated with partial right-sided hepatectomy and multiple thermo-ablative treatments combined with chemotherapy, who manifested a septic fever associated with productive cough and biliptysis. Diagnosis of BBF was confirmed only by hepatobiliary scintigraphy with
99m
Tc-heptoiminodiacetic acid.
The study evaluates the therapeutic efficacy of Strontium-89-chloride (89Sr) and 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) in the palliation of painful bone metastases from breast ...cancer.
Fifty patients with painful multifocal bone metastases from breast cancer entered the study and were randomized into two groups according to the radiopharmaceutical used: 148 MBq 89Sr i.v. (Group A: 25 patients) and 1406 MBq 186Re-HEDP i.v. (Group B: 25 patients). Pain palliation was evaluated on the basis of the Wisconsin pain test improvement at two months and response was graded as complete, partial, minimal or absent. Hematological toxicity and side effects were reported according to WHO guidelines.
The global response rate was 84% (21/25) for 89Sr and 92% (23/25) for 186Re-HEDP, respectively. The onset of pain palliation appeared significantly earlier in Group B (p < 0.0001). The duration of pain relief ranged from two months to 14 months (mean of 125 days with a median value of 120 days) in Group A and from one month to 12 months (mean of 107 days with a median value of 60 days) in Group B (p = 0.39). A moderate hematological toxicity was apparent in both groups. Platelet and white blood cell counts returned to baseline levels within 12 weeks after 89Sr administration and 6 weeks after 186Re-HEDP administration (p < 0.01).
Both 89Sr and 186Re-HEDP are effective and safe in bone pain palliation in breast cancer with the latter showing a significantly faster onset of pain relief.
Background & Aims The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (⩾70 years) ...and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers. Methods Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with90 Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups. Results Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes ( p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume ( p = 0.016) and appeared more likely to receive segmental treatment ( p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1–2 and of short duration. No significant differences in survival between the groups were found ( p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease. Conclusions Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.
This study evaluated the role of (99m)Tc-sestamibi washout in the prediction of pathologic tumor response to neoadjuvant chemotherapy in 30 patients with locally advanced breast cancer.
Two ...(99m)Tc-sestamibi studies were performed before and after chemotherapy for each patient. Early (10 min) and delayed (240 min) planar breast views were acquired after a 740-MBq (99m)Tc-sestamibi intravenous injection, and the washout rate (WOR) was computed. All patients underwent radical mastectomy with pathologic evaluation of the residual tumor size.
The pretherapy (99m)Tc-sestamibi WOR ranged from 14% to 92% (mean +/- SD, 50% +/- 18%). At pathologic examination, 15 patients showed no tumor response to chemotherapy and 15 patients showed an objective response to chemotherapy. The pretherapy (99m)Tc-sestamibi study predicted chemoresistance (WOR > 45%) in 18 of 30 patients and no chemoresistance (WOR < or = 45%) in 12 of 30 patients. When the WOR cutoff was set at >45%, the prognostic performance of the test was indicated by a sensitivity of 100%; a specificity of 80%; positive and negative predictive values of 83% and 100%, respectively; and a likelihood ratio of 5. The repeatability of the test was good, with 80%-93% interreader agreement (kappa = 0.57-0.85). Posttherapy (99m)Tc-sestamibi studies confirmed the pretherapy study prediction in 29 of 30 patients.
(99m)Tc-Sestamibi WOR is a reliable test for predicting tumor response to neoadjuvant chemotherapy. In fact, negative findings (WOR < or = 45%) rule out chemoresistance and positive findings (WOR > 45%) indicate a high risk of chemoresistance.
Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning ...subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC.
Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients.
Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status.
Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.
This study evaluated the effects of low-dose cisplatin plus 89Sr versus 89Sr alone in the treatment of painful bone metastases from prostate cancer, addressing both pain palliation and cytostatic ...effects. Seventy patients with metastatic hormone-refractory prostate cancer were randomized into 2 groups: One group (arm A) received 148 MBq 89Sr plus 50 mg/m(2) cisplatin, and the other group (arm B) received 148 MBq 89Sr plus placebo. After treatment, the patients were followed up until death to evaluate the outcome variables: grade and duration of pain palliation, onset of new painful sites, changes in bone disease, global survival, serum prostate-specific antigen and alkaline phosphatase changes, and hematologic toxicity. Overall pain relief occurred in 91% of patients in arm A and 63% of patients in arm B (P < 0.01), with a median duration of 120 d in arm A and 60 d in arm B (P = 0.002). New painful sites on previously asymptomatic bone metastases appeared in 14% of patients in arm A and in 30% of patients in arm B (P = 0.18). The median survival without new painful sites was 4 mo in arm A and 2 mo in arm B (P = 0.04). Bone disease progression was observed in 27% of patients in arm A and in 64% of patients in arm B (P = 0.01). Median global survival after therapy was 9 mo in arm A and 6 mo in arm B (P = 0.30). Transient and moderate hematologic toxicity, as determined by World Health Organization criteria, was apparent in both arms without significant differences. The addition of a low dose of cisplatin enhances the effect of a standard dose of 89Sr without significant side effects, producing a significant improvement in pain palliation and a cytostatic effect on bone disease.
This study evaluated changes in lymphocyte subsets in patients with thyroid carcinoma who received iodine-131 for diagnostic and therapeutic purposes. Twenty thyroid cancer patients were entered in ...the study after total thyroidectomy: ten patients (group A) underwent whole-body scintigraphy with 185 MBq of (131)I and the other ten (group B) received 3700 MBq of (131)I therapy. All patients were in a hypothyroid state at the time of administration of (131)I and started L-thyroxine 150 microg/day 3 days after (131)I administration. Free and bound triiodothyronine and thyroxine, thyroid-stimulating hormone, thyroglobulin, thyroglobulin antibodies, thyroid peroxidase/microsomal antibodies, white blood cell, lymphocyte counts and lymphocyte subsets were serially determined at baseline and at days 2, 7, 15, 30 and 60 after (131)I administration. Twenty healthy age- and sex-matched individuals were used as a reference population for lymphocyte subset values. In group A only a reduction in NK cells at days 7 (P=0.043) and 15 (P=0.037) was observed. In group B, patients showed a delayed reduction in the total lymphocyte count at days 15, 30 and 60 (P=0.008, 0.004 and 0. 018, respectively), and a decrease in B cells throughout the study (at days 7, 15, 30 and 60: P=0.006, 0.0017, 0.0017 and 0.0017 respectively). A transient decrease in NK cells was observed at days 15 (P=0.025) and 30 (P=0.008). Among T cells, the helper phenotype (CD4+) was mainly affected, resulting in a reduction in the CD4+/CD8+ ratio at day 60 (P=0.046). Comparing the two groups, the numbers of B lymphocytes at day 30 (P=0.023) and NK cells at days 2 (P=0.037) and 30 (P=0.023) were significantly lower in group B. Neither group showed any clinical sign of immunosuppression during the follow-up period. In patients with thyroid cancer the sensitivity of lymphocytes to the effects of (131)I administered for diagnostic or therapeutic purposes depends upon lymphocyte phenotype and (131)I activity. NK cells are the most radiosensitive cells, being reduced even by low (131)I activity. At higher activity all subtypes show a reduction, which is more marked and prolonged for B lymphocytes and, to a lesser extent, for T-helper lymphocytes. These changes do not result in clinically relevant immunosuppression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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