Purpose: This study aimed to detect the M30 neoepitope on circulating tumor cells (CTC) as a tool for quantifying apoptotic CTC throughout disease course and treatment.Experimental Design: An automated sample preparation and analysis platform for computing CTC (CellSearch) was integrated with a monoclonal antibody (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 (CK18) in early apoptosis. The assay was validated using cell lines and blood samples from healthy volunteers and patients with epithelial cancer.Results: M30-positive CTC could be detected in >70% of CTC-positive carcinoma patients, which were free for both chemotherapy and radiologic treatments. The fraction of M30-positive CTC varied from 50% to 80%, depending on the histotype. To investigate the potential application of the M30 CTC assay for the evaluation of response in early phase trials, CTC and M30-positive CTC were enumerated in a small case series of breast cancer patients during treatment. Results indicate that changes in the balance of M30-negative/positive CTC may be used as a dynamic parameter indicating an active disease, as documented by consistent radiologic findings.Conclusions: M30 expression on CTC is detectable by immunofluorescence. The M30-integrated test has potential for monitoring dynamic changes in the quote of apoptotic CTC (in addition to CTC count) to evaluate response in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research, in which there is a pressing need for informative circulating biomarkers.Clin Cancer Res; 16(21); 5233-43. ©2010 AACR.The finding of tumor cells in peripheral blood raises questions as to their metastatic potential. In fact, notwithstanding that a single tumor cell was proved to sustain metastasis in vivo (1), in humans the half-life of circulating tumor cells (CTC) in peripheral blood is estimated at between 1 and 2.4 hours, depending on the mathematical model of the extrapolated curve (2) and on the fact that apoptotic cells significantly contribute to the CTC fraction in breast (3) and prostate cancer (4) patients. On the other hand, a strict correlation was established between CTC count and prognosis (5), and elevated numbers of CTC at any time during therapy was reported to be an accurate indication of subsequent rapid progression and mortality (6). Nevertheless, the phenotypic and biological properties of the CTC that are necessary for the metastatic process are far from clear. Theoretically, CTC should be adapted to shed into peripheral blood and at least some of the CTC should be live cells. Moreover, although the metastatic phenotype may be later acquired as a result of selective pressure exerted at secondary sites, at least some of the CTC should be able to self-renew (7).Addressing the role and mechanism of CTC in the development of metastasis, we investigated whether or not CTC are live cells, considering mainly when and how often the percentage of apoptotic CTC changes throughout disease course and treatment...

From 1977 to 1990, 37 patients with Stage III or IV invasive thymoma (20 men and 17 women; median age, 40 years of age) were referred for chemotherapy to the Padova Medical Oncology Department. All patients initially received the same regimen (50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (IV) on day 1, 0.6 mg/m2 of vincristine IV on day 3, and 700 mg/m2 of cyclophosphamide IV on day 4 [ADOC]), recycling at monthly intervals. No life-threatening side effects were noted. The overall clinical response rate (complete response plus partial response) was 91.8%, with 43% complete remissions. Median duration of response and survival were 12 months (range, 2 to 96+ months) and 15 months (range, 5 to 96+ months), respectively. Seven of the 16 complete remissions were pathologically confirmed at subsequent thoracotomy. Other chemotherapy combinations and radiation therapy have been applied as second-line treatment, achieving only minimal responses. In the opinion of the authors, such chemotherapy deserves evaluation for adjuvant and neo-adjuvant treatment of invasive (and/or inoperable) thymoma due to the high complete response rate and overall response rate.

Background: BRCA1 and BRCA2 are the two major genes responsible for the breast and ovarian cancers that cluster in families with a genetically determined predisposition. However, regardless of the mutation detection method employed, the percentage of families without identifiable alterations of these genes exceeds 50%, even when applying stringent criteria for family selection. A small but significant increase in mutation detection rate has resulted from the discovery of large genomic alterations in BRCA1. A few studies have addressed the question of whether BRCA2 might be inactivated by the same kinds of alteration, but most were either done on a relatively small number of samples or employed cumbersome mutation detection methods of variable sensitivity. Objective: To analyse 121 highly selected families using the recently available BRCA2 multiplex ligation dependent probe amplification (MLPA) technique. Results: Three different large genomic deletions were identified and confirmed by analysis of the mutant transcript and genomic characterisation of the breakpoints. Conclusions: Contrary to initial suggestions, the presence of BRCA2 genomic rearrangements is worth investigating in high risk breast or ovarian cancer families.

Thirty-two patients with stage III or IV invasive thymoma (14 women and 18 men; median age, 40 years) were treated at the Padua Medical Oncology Department from 1977 to 1988. All patients received the following chemotherapy in 4-day courses: 50 mg/m2 of cisplatin intravenously (IV) and 40 mg/m2 of doxorubicin IV on day 1; 0.6 mg/m2 of vincristine IV on day 3; and 700 mg/m2 of cyclophosphamide IV on day 4 (ADOC). The courses were repeated every 3 weeks, and toxic effects were tolerable. The radiologically defined overall clinical response rate (complete plus partial response) was 91% with 47% clinical complete remissions; median time to progression was 11 months (range, 0 to 96) and the median estimated (Kaplan-Meier) progression-free interval was 22 months. Five of the 15 clinical complete remissions were pathologically confirmed at thoracotomy. We believe the ADOC regimen qualifies for adjuvant and preoperative treatment of invasive thymoma due to the high complete response and overall response rates.

FDG PET/CT is more sensitive than CT and CA 15.3 in the evaluation of disease relapse. PET/CT might be considered a complementary imaging technique during follow-up in patients with breast cancer.

Elderly BC patients are highly responsive to ECT and achieve durable local tumor control. Physicians should be aware of possible debilitating side effects, such as pain and skin toxicity. Performance status and frailty screening could be a helpful addition to improve patient selection.

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Elderly BC patients receive much less adjuvant chemotherapy, according to each prognostic factor. N+ HR- disease probably represents the most reasonable indication. As the toxicity of the CMF regimen frequently caused interruption of treatment, alternative regimens should be assessed in this age class.