Postsurgical Pyoderma Gangrenosum in a Breast Cancer Patient: A Case Report and Literature Review.

Pyoderma gangrenosum is a rare skin necrotizing disease that can arise on a site of surgical trauma. Its pathogenesis has recently been related to dysregulation of the immune system, with inflammatory bowel disease representing the most commonly underlying systemic conditions. Several authors have also reported an association with solid malignancies (especially gastrointestinal and breast cancer). We describe the case of a 39-year-old patient diagnosed with a locally advanced, triple-negative breast cancer who developed a pyoderma gangrenosum on the surgical wound after a CVC implant with systemic complications. As the diagnosis and management of postsurgical pyoderma gangrenosum can be challenging for clinicians, underlying conditions as autoimmune disease and solid tumors have to be considered in order to guide treatment.

Neoplastic Pericardial Effusion: A Monocentric Retrospective Study.

Background: Neoplastic pericardial effusion (NPE) is a life-threatening condition that can worsen clinical outcome in cancer patients. The optimal management of NPE has yet to be defined because randomized studies are lacking. Objective: We report a retrospective monoinstitutional experience describing characteristics, management and prognostic factors in NPE patients. Design: We reviewed clinical, pathological, and echocardiographic features, therapeutic strategies, and outcome in NPE patients referred to our institute from August 2011 to December 2017. Measurements: Twenty-nine patients with NPE from solid tumors have been identified: 21 lung, 5 breast, and 3 other cancer patients. Results: Median age was 62 years. Most of the patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 (69%) and a symptomatic NPE (69%). In 52% of patients NPE was detected at first diagnosis of metastatic disease, and in 20% of patients pericardium was the only site of metastases. Most of the patients (62%) received systemic therapy, 28% received combined locoregional and systemic therapy, and 10% received locoregional therapy alone. Median overall survival (OS) from NPE diagnosis was 3.9 months. Patients with PS ≥2 had worse OS than patients with better PS <2 (hazard ratio [HR] 3.56, IC 95% 1.19-10.65, p 0.02). Older age, extrapericardial disease, and NPE at progression showed a trend of association with worse OS. Patients treated with locoregional therapy alone showed the shortest median OS (p 0.05). Conclusions: NPE is related to dismal prognosis. Poor PS significantly worsens survival and influences therapeutic approaches. Randomized studies are required to investigate prognostic factors and appropriate clinical management for patients with NPE.

Patterns of Fertility Preservation and Pregnancy Outcome After Breast Cancer at a Large Comprehensive Cancer Center.

BACKGROUND: In the last decades, long-term outcomes of breast cancer (BC) patients have improved, raising new survivorship issues, including fertility preservation and safety of pregnancy after BC. This study assesses evolution in patterns of fertility discussion/preservation over time and reports pregnancy outcomes in a cohort of young BC patients. METHODS: A retrospective cohort of 590 BC patients aged ≤40 diagnosed between 2000 and 2016 at a large cancer center was identified. Fertility counseling and preservation patterns for patients receiving chemotherapy were analyzed and compared for two cohorts: 2004-2006 and 2014-2016 (total n = 161). Outcomes were reported for patients with documented pregnancy after BC. RESULTS: Significantly, more patients diagnosed in 2014-2016 had evidence of discussion on fertility issues and/or application of fertility preservation techniques versus patients diagnosed in 2004-2006 (82.9% vs. 66.0%, p = 0.017). In particular, there was a significant difference in rate of documented fertility issues discussion (67.6% vs. 34.0%, p < 0.001). Age >35 and parity were associated with lower rates of fertility discussion/preservation. However, rates significantly improved over time (77.6% in 2014-2016 vs. 58.1% in 2004-2006 for patients aged >35, p = 0.046; 80.7% in 2014-2016 vs. 57.6% in 2004-2006 for patients with children at diagnosis, p = 0.018). Twenty-six patients with pregnancy after BC were identified; eight delivered at the age of >40. No complications for women or newborns were reported. Only two patients experienced BC relapse. CONCLUSIONS: In this small retrospective cohort, no safety concerns were identified for pregnancy after BC. The importance attributed by clinicians to address fertility issues has increased over time.

Diagnostic and prognostic impact of fluorine-18-fluorodeoxyglucose PET/CT in preoperative and postoperative setting of breast cancer patients.

PURPOSE: The aim of this study was to assess the diagnostic and prognostic value of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in patients with breast cancer (BC) in the preoperative and the postoperative setting. PATIENTS AND METHODS: Between 2011 and 2015, we prospectively enrolled 275 patients (mean age: 53 years) with BC (stage I-III; triple-negative or HER2-positive cancer). One-hundred and forty-nine (54.2%) patients underwent F-FDG PET/CT before neoadjuvant therapy and 126 (45.8%) after surgery and before any additional adjuvant therapy. The patients were followed for a median period of 44 (2-57) months. The different effects of PET/CT on the presetting and postsetting phase form a therapeutic and prognostic point of view were assessed by χ, by Kaplan-Meier, and Cox-regression analyses. RESULTS: In the preoperative setting, PET/CT provided additional diagnostic information in 42/149 (28%) patients. In particular, 17/70 (24%) patients at stage III were converted into stage IV and 4/68 (6%) at stage II were upstaged to IV. In the postoperative setting, PET/CT upstaged the disease in both stage IIIC and stage IV in 14/126 (11%) cases. At the end of follow-up, 28/271 (10%) patients died from BC and 40 (15%) had a recurrence of disease. On Kaplan-Meier analysis, patients with a positive PET/CT other than the primary tumor site showed both a worse overall survival and a worse disease-free survival compared with their counterpart (76 vs. 92%; P=0.063 and 65 vs. 100%; P<0.001). Conversely, in the postoperative setting, no differences in overall survival and disease-free survival were found between patients with positive and negative PET/CT findings (both P>0.05). On multivariate Cox-regression analysis, a positive PET/CT was a significant predictive factor of a poor prognosis in the preoperative setting. The significance was lost in the postoperative setting. CONCLUSION: In the preoperative setting, PET/CT can provide additional diagnostic and prognostic information. Conversely, in the postoperative setting, PET/CT adds diagnostic information, but does not provide any adjunctive prognostic assessment.

Staging of locally advanced breast cancer and the prediction of response to neoadjuvant chemotherapy: complementary role of scintimammography and 18F-FDG PET/CT.

BACKGROUND: The primary endpoint of the study was to established the role of sestamibi scintimammography and PET/CT findings in locally advanced breast cancer (LABC) before neoadjuvant systemic therapy (NST) in different histological subtypes. The secondary endpoint was to determine the role of FDG PET/CT as multi-drug resistance marker. METHODS: From January 2012, we prospectively enrolled 51 consecutive women (median age: 49 years; range: 27-76 yrs) with a biopsy-proven LABC. All patients underwent both sestamibi scintimammography and FDG PET/CT within one week before to start NST. Both examinations were qualitatively and semiquantitatively analysed. For scintimammography we calculated the tumor to background ratio (T/B) and the most intense uptake of the tumor to background ratio (I/B) according the following formula: T/B=[cntsT-cntsB]/ [cntsB] and I/B [cntsI-cntsB]/[cntsB]. Furthermore, the percentage washout index (WO) for T and I were obtained, according to: WOT,I= [cntsT,I]early image-[cntsT,I]delayed image/[cntsT,I]early image. Maximum and average (avg) standardized uptake value (SUV) was computed by PET/CT, using a region of interest. Patients who had an evidence of systemic metastases or a second active cancer at imaging scans, were excluded. At the end of pre-operative therapy, the response to therapy was assessed by the analysis of surgical specimen and then correlated with both scintimammographic and PET/CT data. RESULTS: Based on the inclusion criteria, the final analysis was performed in 49 patients. Scintimammography and PET/CT showed a sensitivity of 100% for the evaluation of primary cancer, while PET/CT showed a slightly higher detection rate for axillary lymph node than scintimammography. According to the biological pattern, SUVmax and SUVavg resulted significantly different among histological subtypes, whereas scintimammographic data did not. At the end of neo-adjuvant therapy, pathological complete response was obtained in 12 (24.4%) patients, while 37 had a partial or no response to NST (identified as no-responders). On the basis of histopathological response to NST, median WOI resulted significantly lower in responders than non-responders (30.5% vs. 44%; P=0.027). Conversely, SUVmax and SUVavg were significantly higher in responders than non-responders (all P<0.05). In this latter subset of patients, high WOTs were associated with low SUVs. On the contrary, in responder group, high SUVs were reported particularly for high WOT values. CONCLUSIONS: Scintimammography with sestamibi did not accurately determine the responsiveness to therapy. FDG PET/CT is more accurate in the prediction of response to therapy, particularly in the aggressive LABC subtype. Moreover, semiquantitative data by FDG PET seems to be linked with the chemosensitivity to NST.

Beyond breast specific-Graded Prognostic Assessment in patients with brain metastases from breast cancer: treatment impact on outcome.

Brain metastases are a serious relatively common complication of breast cancer. We evaluated prognostic factors for survival after diagnosis of brain metastases from breast cancer in a contemporary cohort of patients. Patients diagnosed with breast cancer brain metastases at our institution between 1999 and March 2016 were evaluated. Overall survival was defined as time from brain metastasis diagnosis to death or last follow-up. Patients were classified according to the Breast cancer-specific Graded Prognostic Assessment (BS-GPA), based on age, Karnofsky performance score and breast cancer phenotype. 181 patients were identified. Tumor phenotype distribution was as follows: triple negative (TN, 18.8%), hormone receptor (HR)-HER2+ (16.6%), HR+HER2+ (23.2%) and HR+HER2- (30.9%), not available (10.5%). Median overall survival from brain metastasis diagnosis was 7.7 mos (95% CI 5.4-10.0 mos). Although TN patients experienced the worse outcome, no significant difference was observed across tumor phenotypes (median 5.1, 7.7, 11.0 and 8.6 months in TN, HR-HER2+, HR+HER2+, HR+HER2-, p = 0.081). The BS-GPA index was significantly associated with overall survival (median 18.8, 8.8, 6.2 and 3.6 months, respectively, for BS-GPA categories 3.5-4, 2.5-3, 1.5-2 and 0-1, p = 0.014). Increased number of local treatments for brain metastasis (radiotherapy or neurosurgery) or the administration of systemic therapy after brain metastasis diagnosis were also significant predictors of better overall survival (p < 0.001) and, when evaluated in multivariate analysis with BS-GPA, both added independent prognostication beyond BS-GPA. Patient-related features, tumor phenotype and multimodal treatments all independently contribute to modulate prognosis of patients diagnosed with breast cancer brain metastases.

Braf mutation in interdigitating dendritic cell sarcoma: a case report and review of the literature.

Interdigitating dendritic cell sarcoma is an extremely rare tumor. The diagnosis is difficult and is based on clinical, pathological and immunohistochemical evaluation. Differential diagnosis includes melanoma, mesenchymal and hematological malignancies. The mainstay of treatment is surgery for limited disease and different chemotherapy combinations have been tested for advanced disease. No evidence from prospective trials is currently available. We report the case of a 59 year-old male patient who experienced axillary lymphadenopathy with initial diagnosis of large-cell lung cancer on tumor biopsy. He underwent surgical resection with radical intent. Pathological diagnosis of interdigitating dendritic cell sarcoma was obtained on surgical samples. Nine months after radical surgery, he experienced systemic recurrence of disease and underwent chemotherapy with epirubicin and ifosfamide for 4 courses. During chemotherapy, he developed brain disease progression and underwent whole-brain radiotherapy. Systemic progression was then observed and molecular characterization was performed. B-RAF evaluation resulted positive for V600E mutation and the patient was treated with Vemurafenib according to molecular findings. He thus obtained initial clinical benefit but eventually died of brain hemorrhage. In conclusion, we report a case of B-RAF mutation detected in an interdigitating dendritic cell sarcoma patient treated with targeted therapy. B-RAF pathway could have a role in pathogenesis and evolution of this rare disease and could open new perspectives of treatment.

Could semiquantitative FDG analysis add information to the prognosis in patients with stage II/III breast cancer undergoing neoadjuvant treatment?

PURPOSE: We investigated whether maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and whole-body (WB) SUVmax, WB MTV and WB TLG measured by (18)F-FDG PET/CT could improve prognostic stratification in patients with stage II/III breast cancer (BC). METHODS: We prospectively enrolled 99 consecutive women (median age 50 years, range 27 - 77 years) with pathologically proven stage II/III BC who underwent pretreatment FDG PET/CT. WB SUVmax, WB MTV and WB TLG were measured in all malignant lesions. Survival was analysed using the Kaplan-Meier method. Cox proportional hazards models were constructed to test for relationships among WB SUVmax, WB MTV, WB TLG, and overall survival (OS) and disease-free survival (DFS), after adjustment for age, and histopathological and immunohistochemical features (oestrogen/progesterone and HER2 expression, proliferation index and grade). RESULTS: The median values of WB SUVmax, WB MTV and WB TLG were 16.2 (range 1.5 - 33.1), 14 cm(3) (range 0.03 - 708.6 cm(3)) and 62.5 (0.06 - 3869.4), respectively. All WB semiquantitative values were higher in patients with higher TNM stage, although not significantly (all p > 0.05). The median follow-up for surviving patients was 30 months, with a range of 13 - 45 months. Both PFS and OS of patients with low WB SUVmax, WB MTV and WB TLG were longer than that of patients with high WB values for progression, although not statistically significant. However, stratifying the patients in accordance with the stage of disease, both PFS and OS were significantly lower in patients with high WB TLG and stage III than in patients with stage II (p < 0.05). In multivariate analyses, WB MTV and WB TLG were independent prognostic factors for PFS (hazard ratio 1.004, 95% confidence interval 1.002 - 1.006, p < 0.001, and hazard ratio 1.001, 95% confidence interval 1.000 - 1.001, p = 0.011, respectively). CONCLUSION: The addition of WB TLG to clinical data may provide a more detailed prediction of outcome in patients with stage III BC. Moreover, WB MTV and WB TLG are independent factors predicting recurrence of BC. On the contrary, WB SUVmax has poor prognostic significance in this cohort of patients.

Use of a portable gamma camera for guiding surgical treatment in locally advanced breast cancer in a post-neoadjuvant therapy setting.

The aim of the present study was to assess the feasibility of a portable gamma camera (PGC) for guiding surgical treatment in locally advanced breast cancer (LABC) after neoadjuvant therapy (NT). Since January 2012, a PGC (Sentinella 102, ONCOVISION) has been available in our center. We planned to perform a feasibility monocentric prospective study involving 15-20 patients with LABC for assessing the diagnostic performance of this PGC after NT (Breast Cancer Surgery-S102). Before the surgical treatment and at the end of NT an injection of 99mTc-Sestamibi (100-150 MBq) was made. Conventional scintimmamography (SMM) and Sentinella 102 images were obtained from 18 patients. 10 (55.5 %) patients showed a focal uptake of tracer in the breast or lymph nodes before or after the surgical excision (on histological specimen), while 8 did not. The histological specimen concluded for a complete response to NT in 4 (22.2 %) patients and for a partial or no response to treatment in the remnant 14 subjects. The specificity and false-negative rate of the Sentinella 102 compared to SMM were 100 % for both and 38 % vs. 60 %, respectively. The global diagnostic accuracy of Sentinella 102 was: 66.7 % (95 % confidence interval: 44.88-88.44 %). The present feasibility study shows how a new nuclear imaging device can be useful in the operating theatre for guiding a radical surgery approach in patients with LABC after NT.

Correlation between cancer antigen 15.3 value and qualitative and semiquantitative parameters of positron emission tomography/computed tomography in breast cancer patients.

BACKGROUND: The association of PET/CT and tumor markers can be considered complementary, since any significant increases of tumor markers can indicate the presence of disease while PET/CT is able to detect and describe the tumor sites. In this retrospective, single-institution study, we determine the correlation between cancer antigen (CA) 15.3 value and qualitative and semi-quantitative PET/CT data in breast cancer (BC) patients. METHODS: 193 BC patients (median age 61 yrs) already treated with primary treatment (surgery and others) were identified through institutional databases. All patients underwent PET/CT for increase in tumor markers, post-therapy evaluation, restaging and doubtful conventional imaging for disease relapse. The CA15.3 values before PET/CT scan were collected for all patients. Clinical outcome was defined as presence or absence of disease recurrence based on follow-up data (histological or imaging findings). CA15.3 quartile values and qualitative and semi-quantitative (maximum Standardized Uptake Value - SUVmax) PET/CT findings were compared with chi-square test and linear regression analysis. RESULTS: The mean value of CA15.3 was significantly higher in patients with positive than negative PET/CT (67.51±120.92 vs. 25.54±17.54, p<0.005). PET/CT was positive in 107 (55%) and negative in 86 (45%) patients; CA15.3 value was considered abnormal (≥ 31 UI/mL) in 85 (44%) patients; 57 of them showed positive PET/CT while 28 a negative scan (67 vs. 33%, p<0.05). In all 193 patients, the disease recurrence was found in 71 (37%), whereas 122 (63%) were disease-free. The diagnostic accuracy of PET/CT in all 193 patients was 74%. Among patients with normal CA15.3 value (n=108), 50 showed positive PET/CT; 24 out of these latter 50 patients (48%) had recurrence of disease. The combination of the highest quartile of CA15.3 (value>45 UI/ml) and FDG PET/CT determined high sensitivity and accuracy (92% and 82%, respectively) but a low specificity (50%) for restaging BC patients. The highest specificity (~ 70%) was found when PET/CT and 2nd quartile of CA15.3 (value: 12.95-25) were associated. No correlation between CA15.3 values and SUVmax was found (p=0.489); whereas a trend in increase of the CA15.3 value and SUVmax in the presence of visceral and no-visceral site of disease (22.4±16.2, 64.9±108 and 6.4±4.2, 8.2±5.1, respectively) was identified. CONCLUSIONS: The value of CA15.3 and PET/CT findings are consistently complementary. About 25% of BC patients with a negative CA15.3 value had a positive PET/CT and disease relapse. SUVmax and CA15.3 values are not correlated.

Bleomycin electrochemotherapy in elderly metastatic breast cancer patients: clinical outcome and management considerations.

PURPOSE: To evaluate the efficacy and toxicity of electrochemotherapy (ECT) in elderly metastatic breast cancer (BC) patients. METHODS: Retrospective analysis of 55 patients with superficial metastases who underwent ECT according to the European Standard Operative Procedures of electrochemotherapy. Treatment schedule consisted of intravenous or intratumoral bleomycin followed by locally delivered electric pulses. Statistical comparisons were performed between two groups: the patients aged <70 years (n = 27) and those ≥70 years (n = 28). Treatment outcomes were as follows: complete response (CR) rate, local progression-free survival (LPFS), new lesions-free survival (NLFS), toxicity and patient compliance. RESULTS: Patient groups were comparable for clinical-pathological features, except for the number of comorbidities (P < .001). The median follow-up was 32 months (range 6-53). Overall, CR rate was 40 % and was significantly higher in elderly patients (57 vs. 26 %, P = .023) and in patients with better performance status (PS = 0-1, 53 vs. PS = 2, 21 %, P = .048), although local tumor control showed a trend for lower values (2-year LPFS, 67 vs. 93 % among elderly and young patients, respectively; P = .061). Older women seemed less likely to progress outside the ECT field (2-year NLFS, 39 vs. 30 %, P = .075), but discontinued treatment more frequently due to impaired performance status (P = .002). Local pain was graded ≥3, according to a 10-point visual analog scale, by 16/28 (57.1 %) and 8/28 (28.6 %) elderly patients at 4 and 8 weeks, respectively. Wound debridement was required in 5/28 (18 %) older women, due to G3 skin ulceration. CONCLUSIONS: 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.

FDG avidity at PET/CT during adjuvant hormonal therapy in patients with breast cancer.

BACKGROUND: We aim to retrospectively evaluate the impact of hormone therapy (HT) on FDG avidity of metastatic lesions in patients with breast cancer (BC) undergoing PET/CT. PATIENTS AND METHODS: Three hundred eight patients with BC were scanned with PET/CT at 2 Italian institutions (mean time from diagnosis 4 yrs, range: 1-24 yrs). Main indications for PET/CT were elevation of tumor markers (34.4%) and clinical or radiological suspicion of relapse (65.6%). The diagnostic accuracy of FDG PET/CT was computed according to the standard method. Student t test was used to assess the mean differences between the study groups, whereas categorical data were compared with chi-square test. Significance was set at P <0.05. RESULTS: Two hundred sixty-four patients with positive estrogen receptor and who had received adjuvant HT were included in the analysis. At the time of PET/CT scan, HT was ongoing in 176 patients (66.7%) and 88 (33.3%) had completed adjuvant HT. Ninety-eight (55.7%) patients on HT and 59 (67%) off HT had a positive PET/CT; therefore, the scan resulted negative in the remaining 107 patients, 78 and 29 on and off HT, 44.3% and 33%, respectively (P < 0.001). At a median follow-up of 7 months (range 1-48 mos), disease recurrence was confirmed in either clinical or radiological examinations in 126 (47.7%) patients; 72 (40.9%) versus 54 (61.4%) patients on and off HT, respectively (P < 0.005). True-positive PET/CT results were found in 82% and 91% of patients on and off HT, respectively, whereas it failed to identify disease relapse in 13 (18%) and 5 (9%) patients on and off HT, respectively. CONCLUSIONS: In our series, FDG PET/CT shows a similar diagnostic accuracy in detecting disease relapse between patients with BC on adjuvant HT versus those who have completed therapy. These preliminary results suggest that the glucose metabolism is not altered by hormonal suppression at the time of the scan.

Preliminary monocentric results of biological characteristics of pregnancy associated breast cancer.

PURPOSE: We performed a mono-institutional study for evaluating the biological data, such as p53, Ki67 and BRCA mutations, as well as clinical characteristics of pregnancy associated breast cancer (PABC), its therapeutic management and the prognosis in a small cohort of patients. MATERIALS AND METHODS: We retrospectively examined 26 patients with PABC. Clinical and histopathological characteristics along with Ki67, p53 and BRCA mutations were analysed. Information about chemotherapy, surgery and radiotherapy was recovered. Data about long-term prognosis was registered and computed by Kaplan-Meier analysis. RESULTS: Of 26 patients, 17 (65%) were considered as having a locally advanced breast cancer. The majority of them (65.4%) had a ductal invasive carcinoma. Oestrogen and progesterone receptors were positive in 13 (50%) patients, resulting both negative in four (15.4%) subjects. HER-2 was positive in 5 subjects (19.2%). Ten patients underwent conservative surgery treatment, and 14 were sent to radical mastectomy (38 vs. 54%) associated with axillary lymph node dissection in 18 cases. Many patients (65%) were further treated with adjuvant chemotherapy and/or hormone therapy. Eight out of 11 patients undergoing the evaluation of BRCA mutation were positive while only 2 out of 3 patients had a mutation of p53. After a median follow-up of 110 months (range: 8.2-1227 mo.), 18 women were still alive, six patients (25%) died and two were lost. Three patients showed a loco-regional recurrence, after a median period of 26 months (range: 2-42 mo.). Distant metastases verified in six patients after a median period of 12.5 months (range: 2-108 mo.). The prognosis was less favourable in BRCA mutated patients than no-BRCA mutated group, although not statistically significant. CONCLUSIONS: In women with PABC, the initial stage of disease is more advanced requiring more aggressive treatment.

Tumor marker-guided PET in breast cancer patients-a recipe for a perfect wedding: a systematic literature review and meta-analysis.

INTRODUCTION: Early detection of breast cancer (BC) recurrence is a fundamental issue during follow-up. Although the utilization of new therapeutic protocols aimed at reducing the recurrence risk is defined, the diagnostic approach for early detection remains to be clarified. We aim to provide a critical overview of recently published reports and perform a meta-analysis on the use of tumor markers in BC patients as a guide for fluorodeoxyglucose positron emission tomography (PET) imaging. METHODS: Medline and Google Scholar were used for searching English and non-English articles that evaluate the role of PET in BC recurrence when an increase in tumor markers is found. All complete studies were reviewed; thus, quantitative and qualitative analyses were performed. RESULTS: From 2001 to May 2011, we found 19 complete articles that critically evaluated the role of PET in BC recurrence detection in the presence of elevated tumor markers. The meta-analysis of the 13 studies provided the following results: pooled sensitivity 0.878 (95% CI: 0.838-0.909), pooled specificity 0.693 (95% CI: 0.553-0.805), and pooled accuracy 0.828 (95% CI: 0.762-0.878). CONCLUSIONS: The current experience confirms the potential of fluorodeoxyglucose PET, and in particular of PET/CT, in detecting occult soft tissue and bone metastases in the presence of a progressive increase of serum tumor markers in BC patients, but this should be better defined in the current practical recommendations.

Could the serial determination of Ca15.3 serum improve the diagnostic accuracy of PET/CT?: results from small population with previous breast cancer.

OBJECTIVES: A single value of tumor marker elevation is not used for the diagnosis of breast cancer (BC) relapse, whereas the serial measurements which confirm a persistent Ca15.3 increase can represent an early signal of tumor relapse, even if described in asymptomatic patients without any other clinical or instrumental signs of cancer. The aim of this study was to assess the relationship between serial measures of Ca15.3 and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) findings in patients with already treated BC during follow-up. METHODS: We retrospectively selected 60 patients (mean age 62 ± 11 years) with previous history of BC, already treated with surgery and other treatments. Three serial measures of Ca15.3 were collected within 1 year before PET/CT examination, respectively, at 12-9 months (297 ± 30 days), 9-3 months (154 ± 51 days) and 3-0 months (46 ± 28 days). Clinical outcome or imaging follow-up data were used to define disease relapse. The increase in tumor marker value was compared with PET/CT results and disease relapse. Coefficient of variation (CV) and ROC curves were used. Disease-free survival (DFS) curves were computed by Kaplan-Meier method. RESULTS: PET/CT was negative in 36 (60%) and positive in 24 (40%) patients. The median time between initial treatment and PET/CT was 3 years. CV of the Ca15.3 serial determinations was significantly higher in patients with positive than negative PET/CT (39 vs. 24%, p < 0.05). Disease relapse was found in 25 (42%) patients, of these 21 (88%) had positive PET/CT. ROC analyses showed that an increase of Ca15.3 between the 2nd and 3rd measures have better individuated positive PET/CT and disease relapse (AUC 0.65 and 0.64, respectively; p < 0.05). DFS was higher in patients with negative than positive PET/CT (65 vs. 15%, p < 0.05). CONCLUSIONS: Serial increase of Ca15.3 could be considered optimal to address FDG PET/CT examination during BC patients follow-up. PET/CT performed just on time might allow, earlier and with higher diagnostic accuracy, the detection of disease relapse in BC patients.

Tumour markers and FDG PET/CT for prediction of disease relapse in patients with breast cancer.

PURPOSE: The aim of the study was to assess the role of CA 15.3, CT and positron emission tomography (PET)/CT in patients with breast cancer and suspected disease relapse after primary treatment. METHODS: We studied 111 consecutive patients (mean age 61 ± 12 years) with previous breast cancer, already treated and with clinical or biochemical suspicion of disease relapse. All patients underwent CT and (18)F-fluorodeoxyglucose (FDG) PET/CT. In all patients, the value of CA 15.3 was compared to PET/CT and CT. The final diagnosis of relapse was established by invasive and noninvasive follow-up and was compared with CA 15.3, CT and PET/CT results. Univariate and multivariate analyses were used to identify the independent predictors of disease relapse and receiver-operating characteristic (ROC) curve for the identification of optimal CA 15.3 cutoff. RESULTS: Of all patients, 40 (36%) showed an increased CA 15.3 value, CT was positive in 73 (66%), whereas at PET/CT imaging 64 (58%) showed positive findings for disease relapse. Of 40 patients with increased marker levels, 22 patients had positive CT and 30 positive PET/CT (55 vs 75%, p < 0.001). At the end of follow-up, recurrence occurred in 32 (29%) patients, 16 (50%) of whom showed high levels of CA 15.3. PET/CT predicted relapse in 26 (81%) patients, whereas CT correctly identified 23 (72%). At univariate analysis, recurrence was significantly associated with high CA 15.3 values (p < 0.05) and positive PET/CT (p < 0.005). At multivariable analysis only positive PET/CT remained an independent predictor of disease relapse (p < 0.05). ROC analysis showed an optimal cutoff point for CA 15.3 of 19.1 U/ml (AUC 0.65, p < 0.01) to individuate positive PET/CT. CONCLUSION: 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.

Intrathecal chemotherapy in lymphomatous meningitis.

Central Nervous System (CNS) involvement in lymphoma can occur whether at diagnosis or, more often, at the progression or recurrence of disease and the most frequent clinical manifestation is lymphomatous meningitis (LM). The first risk factor for LM development is the histotype, with the highest incidence for highly aggressive non-Hodgkin's lymphomas (NHL) such as Burkitt's lymphoma (BL) and lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and the lowest for indolent NHL. LM prophylaxis in aggressive NHL (other than BL and LBL/ALL) is a much debated question, because the identification of specific risk factors remains controversial. Moreover, there is not a consensus if the LM prophylaxis should consist of systemic chemotherapy (CT), intrathecal (i.t.) CT or both. In case of LM, the i.t. CT has a key role, but there is not a consensus on treatment schedule. Newer intensified regimens and rituximab lead to reconsider the whole approach to LM.

M30 neoepitope expression in epithelial cancer: quantification of apoptosis in circulating tumor cells by CellSearch analysis.

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.

Correlation between magnetic resonance imaging and histopathological tumor response after neoadjuvant chemotherapy in breast cancer.

AIM: To evaluate the accuracy of magnetic resonance imaging in assessing tumor response following neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIALS AND METHODS: Twenty-six patients entered a phase II study of neoadjuvant chemotherapy, undergoing bilateral breast magnetic resonance imaging before therapy and before surgery. Tumor response was classified using RECIST criteria, using tumor size at magnetic resonance imaging. The latter was then compared to residue found at histopathological examination. RESULTS: Magnetic resonance imaging showed 6 (23%) complete responses, 17 (65%) partial responses, 3 (11.5%) disease stabilizations and no disease progressions. Twenty-three tumors (88.5%) were considered responsive and 3 (11.5%) unresponsive. Pathological tumor response was: 6 complete responses (23%), 17 partial responses (65%), 2 stable disease (8%), 1 progression (4%). When results of the preoperative magnetic resonance imaging were compared to pathological tumor response, magnetic resonance imaging overestimated tumor size in 12 cases (46%) and underestimated it in 9 (35%). However, preoperative magnetic resonance imaging failed to detect invasive tumor in 2 false-negative cases (8%), 1 of which was multifocal. Mastectomy was performed in 12 cases: 1 case of disease progression even though the neoplasm appeared smaller at magnetic resonance imaging, 3 cases with stable disease, and 4 cases with T3 or T4 disease. The 9th patient was T2N2 with initial retroareolar disease and negative magnetic resonance imaging after chemotherapy. The 10th patient, affected by lobular cancer, was in partial remission but was T3N1. The 11th patient was 57 years old but was not interested in conservative surgery. The 12th patient requested bilateral prophylactic mastectomy due to her positive family history of breast cancer. CONCLUSIONS: Magnetic resonance imaging of the breast allowed conservative surgery in 54% of the patients. This low value is primarily due to overestimation of tumor size, with a negative predictive value of 67% in our population. However, surgeons were able to choose conservative surgery with relative safety in cases of small residual disease.