¹8F-choline positron emission tomography/computed tomography-driven high-dose salvage radiation therapy in patients with biochemical progression after radical prostatectomy: feasibility study in 60 patients.

PURPOSE: 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). METHODS AND MATERIALS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Quantitative molecular analysis of sentinel lymph node may be predictive of axillary node status in breast cancer classified by molecular subtypes.

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.

Detection of a suspected bronchobiliary fistula by hepatobiliary scintigraphy.

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.

153Sm-EDTMP for bone pain palliation in skeletal metastases.

153Sm-ethylene diamine tetramethylene phosphonate (EDTMP) is a widely available and extensively tested radiopharmaceutical for systemic radionuclide therapy in patients with symptomatic multiple skeletal metastases. Its use is approved for any secondary bone lesion which has been shown to accumulate (99m)Tc-methylene diphosphonate, including breast carcinoma. The molecule is stable in vitro and upon injection more than 50% of the dose is avidly fixed by lesional and non-lesional bone, with the rest being rapidly eliminated unchanged via the urine. The short half-life (46.3 h), the relatively low-energy beta emissions (E(ave)=233 keV) and the gamma emission (103 keV) make (153)Sm a very attractive radionuclide, allowing therapeutic delivery of short-range electrons at relatively high dose rates with external imaging to corroborate biodistribution and possible dosimetric estimates. For a standard dose of 2,590 MBq/70 kg, the estimated radiation dose to metastases is 86.5 Gy. Critical organs are the bladder wall (2.5 Gy/2,590 MBq) and red marrow (4 Gy/2,590 MBq), with the latter being the critical factor in clinical practice as the dose-limiting factor is marrow radiotoxicity. The therapy has, however, proved safe provided that the platelet count exceeds 100 x 10(9)/l and the white blood cell count exceeds 3.5 x 10(9)/l. Clinical data obtained in fewer than 250 patients, within several studies, lead to the following conclusions: a dose of 37 MBq/kg has a better therapeutic ratio than a dose of 18.5 MBq/kg; the mean pain palliation rate after a single treatment in breast cancer is about 80%; toxicity is generally mild and transitory; and re-treatments are effective and safe provided that haematological values have fully recovered.

Prognostic value of (99m)Tc-sestamibi washout in predicting response of locally advanced breast cancer to neoadjuvant chemotherapy.

UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: (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.

Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial.

UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.