[Metastatic urinary bladder involvement in breast cancer]. / AFECTACIÓN VESICAL METASTÁSICA DEL CÁNCER DE MAMA.

OBJECTIVE: To contribute to the literature with three unusual cases of primary breast tumor with metastasis to the urinary bladder. METHODS: Presentation of the three clinical cases and bibliographic review. RESULTS: Three women, with an average age of 49.3 years, were diagnosed with invasive lobular breast carcinoma. Two of them suffered from hematuria after being diagnosed with breast cancer. The third patient was diagnosed incidentally after a routine CT scan. Upon diagnosis of the bladder metastases, they already had metastasis in other locations. The treatment of the three cases was palliative. The cause of death was due to additional pathologies. CONCLUSIONS: The presence of bladder metastases due to breast cancer is infrequent. The appearance of urinary tract symptoms in these patients requires a diagnostic study in order to rule out metastases.

Adjuvant chemoradiation in gastric cancer: long-term outcomes and prognostic factors from a single institution.

BACKGROUND: Adjuvant chemoradiotherapy (CRT) improves relapse-free (RFS) and overall survival (OS) in patients with resected gastric cancer. However, difficulties in standardizing an optimal surgical approach and a perceived higher toxicity compared with the perioperative approach have limited its widespread application in Europe. The aim of our study was to assess toxicity and long-term outcomes of adjuvant CRT at our institution. METHODS: A retrospective review (September 2001-January 2012) was completed of patients with resected gastric cancer who received adjuvant CRT (Macdonald regimen). Adverse events and completion rates, RFS and OS were estimated. Univariate and multivariate analyses of prognostic factors for OS were performed. RESULTS: Eighty-seven patients were included. Most had diffuse (52%) and locally advanced tumors (stage III-IV; 66.7%). D2 lymphadenectomy was performed in 80.5%. The most frequent grade 3-4 toxicities were gastrointestinal (28%) and stomatitis (20%), with 78.2% completing treatment. With a median follow-up of 115 months, 58.5% had relapsed, most of them distantly. Median RFS and OS were 9 and 24 months, respectively. Univariate analysis showed that performance status, stage and lymph node burden were significant factors for OS. In the multivariate study, only stage and lymph node burden remained as independent OS predictors. CONCLUSIONS: Our implementation of the Macdonald regimen achieved worse outcomes than those reported in the INT-0116 trial. The rate of distant relapse remains unacceptably high. Higher rate of positive lymph nodes and of diffuse tumors could explain some differences. The use of perioperative chemotherapy, especially in patients with a poorer prognosis, might improve these results.

Feasibility and safety of a modified outpatient regimen with intravenous/intraperitoneal chemotherapy for optimally debulked stage III ovarian cancer.

OBJECTIVE: Intraperitoneal (i.p.) chemotherapy improves survival in optimally debulked ovarian cancer patients. However, the need for inpatient administration and the perceived higher toxicity rates compared with standard intravenous chemotherapy have limited its widespread application. Several modified outpatient schemes, such as the Spanish Ovarian Cancer Research Group (GEICO) regimen, have been tested and have reported overall better tolerance with an improvement in completion treatment rates. The aim of our study was to assess the toxicity of the GEICO regimen in patients treated at our institution. METHODS: We reviewed clinical records of stage III ovarian cancer patients with optimally debulked primary cytoreduction surgery that were treated from June 2009 to April 2013 with the GEICO regimen. Patients received intravenous paclitaxel (175 mg/m2) for 3 hours on day 1, i.p. cisplatin (100 mg/m2) on day 2, and i.p. paclitaxel (60 mg/m2) on day 8 every 21 days for a maximum of 6 cycles. RESULTS: Twenty-one patients were identified. In 67% of the patients, i.p. port placement was performed at the primary surgery. The most common grade 3-to-4 toxicities seen were abdominal pain (14.3%) and neurotoxicity (9.5%). Eighteen patients (85.7%) completed the 6 cycles. Three patients stopped chemotherapy because of treatment-related toxicity. There were no serious port-related complications. With a median follow-up of 46 months, median progression-free survival was 23 months (95% confidence interval [11.8-34.6]). Nine patients (42.9%) have relapsed; most relapses were multifocal and extraperitoneal. CONCLUSION: The administration of the GEICO outpatient modified regimen was feasible with a good safety profile. It seems to show less toxicity than previously reported IP chemotherapy regimens. In our institution, port-related complications were infrequent and easily managed. However, further studies are warranted to establish the optimal i.p. regimen in a prospective manner and to validate it in a larger phase 3 trial.

SNPs and taxane toxicity in breast cancer patients.

AIM: In order to identify genetic variants associated with taxanes toxicity, a panel with 47 SNPs in 20 genes involved in taxane pathways was designed. PATIENTS & METHODS: Genomic DNA of 113 breast cancer patients was analyzed (70 taking docetaxel, 43 taking paclitaxel). RESULTS: Two SNPs associated with docetaxel toxicity were identified: CYP3A4*1B with infusion-related reactions; and ERCC1 Gln504Lys with mucositis (p≤0.01). Regarding paclitaxel toxicity: CYP2C8 HapC and CYP2C8 rs1934951 were associated with anemia; and ERCC1 Gln504Lys with neuropathy (p≤0.01). CONCLUSION: Genes involved in DNA repair mechanisms and reactive oxygen species levels influence taxane toxicity in cancer patients treated with chemotherapy schemes not containing platinum. These findings could lead to better treatment selection for breast cancer patients.

Advantages of one step nucleic acid amplification (OSNA) whole node assay in sentinel lymph node (SLN) analysis in breast cancer.

BACKGROUND: The purpose of this study is to present our first results of sentinel node analysis (SLN) by one step nucleic acid amplification (OSNA) in routine clinical practice in our centre and compare them with the results of classic histopathological analysis in a historical cohort from our same institution. METHODS: 407 patients (total study population) with early breast cancer and no clinical nodal involvement underwent SLN biopsy in our institution. The SLN was analysed by OSNA in 164 biopsies. OSNA results were compared with the conventional histopathology study of 244 patients who had undergone SLN biopsy previously. The characteristics of the patients in both groups were evaluated and a comparison was made of the rate of metastases detected by both methods and of the surgical procedures needed in each group. We also investigated the state of non-sentinel lymph nodes if micrometastases where found in SLN. RESULTS: SLN biopsy result was considered as positive in 45 patients (28%) in the OSNA group and in 58 in the historical group (24%). There was no difference in the rate of macrometastases (16,5% for OSNA, 20% for HE) but we found differences in the rate of micrometastases (11% for OSNA and 3,6% for HE p = 0.0007). Axillary lymphadenectomy (ALND) was performed in 43/45 cases in the OSNA group and in 51/58 of the historical group. In all patients diagnosed by OSNA, ALND was performed during the initial surgical procedure. In the historical cohort ALND was performed during the initial surgical procedure in 41 patients and in a second surgical procedure in 10 patients. Patients from both groups with micrometastases in the SLN had no metastases in other nodes when the ALND was performed. CONCLUSIONS: OSNA analysis allows the detection of SLN metastases as precisely as conventional pathology with an increased detection of micrometastases. The OSNA method can reduce the need of a deferred lymphadenectomy.

Paclitaxel and carboplatin treatment for advanced ovarian cancer during pregnancy.

Ovarian carcinoma during pregnancy is a rare event that should be treated. In these cases, due to the lack of information available, doubts about the safety of mother and fetus are present. In this report, a 42-year-old woman who was diagnosed with a stage III ovarian carcinoma received six cycles of chemotherapy with carboplatin and paclitaxel from the 16th until 36th week of gestation. At 38 weeks, a normal male baby was born. There were no abnormalities during birth and during a 2-month follow-up period. This case adds to the available literature and supports the use of these chemotherapy agents during pregnancy, if the risk-benefit balance is appropriate.

Synchronous and metachronous bilateral breast cancer: a long-term single-institution experience.

Bilateral breast cancer (bBC) is the most common 2nd tumor in primary BC patients. However, its natural history is poorly understood as is the effect of previous adjuvant therapies. Between 1980 and 2005, we identified 3757 BC patients treated in our Institution, with 120 (3.2%) cases of bBC, 91 (2.4%) were metachronous BC (mBC), 29 (0.8%) synchronous BC (sBC). sBC defined as found before 3 months of the initial diagnosis. We performed a descriptive and an overall survival (OS) analysis. mBC appeared in young patients with a strong family history of BC. Most were diagnosed mammographically. The risk did not disappear after 15 years of follow-up. In most estrogen receptor (ER)-positive cases, the 2nd tumor was also ER-positive (concordance rate of 91%). No differences were seen according to the previous use of tamoxifen. In ER-negative cases, 43% of mBC were ER-positive. Synchronous BC (sBC) appeared in an elderly population with a strong family history. About 76% were ER-positive. ER status concordance was seen in 62%. There were no statistically significant differences in OS between patients with sBC or those with the 2nd mBC. A shorter time to appearance of the 2nd tumor predicted a worse OS. ER negativity and grade 3 tumors were negative prognostic factors. The risk of mBC does not abate with the pass of time. Contralateral mammographies should form part of follow-up. ER status concordance is high, especially in ER-positive cases. No differences were seen according to previous use of tamoxifen. Shorter disease-free intervals were linked with worse OS.

Magnetic resonance imaging features of the discrete epiphyseal radiolucency: a problem-solving approach to differential diagnosis.

Discrete radiolucencies in the epiphysis of the long bones may be a major radiographic finding in many arthropathies and synovial-based processes, and also in various osteolytic tumors and tumor-like lesions. In addition, a number of miscellaneous bone disorders, particularly infection and avascular necrosis, may present as discrete epiphyseal radiolucencies. Magnetic resonance imaging is frequently used in the diagnostic workup of these lesions. Our purpose was to review and illustrate, in a problem-solving approach, the potential contributions of magnetic resonance imaging in the characterization of discrete epiphyseal radiolucent lesions.

Primary meningeal lymphoma of T-cell origin: a rare presentation of primary central nervous system lymphomas.

Primary meningeal lymphoma is a rare clinical entity. Central nervous system infiltration by systemic lymphoma should always be excluded. Diagnosis can be difficult, and prognosis is usually poor. Most are of B-cell origin. We present the case of a young man with a primary meningeal lymphoma of T-cell origin. He was treated with systemic chemotherapy with high-dose methotrexate and cytarabine and intraventricular chemotherapy. He had a clinical improvement and a complete remission, with a long overall survival. There is no standard treatment for this rare disease. Traditionally, treatment has been based in craniospinal radiation therapy and intrathecal chemotherapy, with poor overall results. More recently, systemic chemotherapy with high-dose methotrexate has been advocated, which could avoid the long-term toxicity of craniospinal radiation therapy, and could improve the prognosis of these patients.

Clinical predictors of severe toxicity in patients treated with combination chemotherapy with irinotecan and/or oxaliplatin for metastatic colorectal cancer: a single center experience.

INTRODUCTION: Little has been published regarding clinical predictors of severe toxicity in patients with metastatic colorectal cancer (CRC) treated with combination chemotherapy (CT) with oxaliplatin and/or irinotecan. MATERIAL AND METHODS: We analyzed retrospectively 142 patients treated between 1996 and 2004 in our center with these regimes with regards to grade 3-4 toxicity and overall survival (OS) rates. Köhne's prognostic classification could be applied in all patients. RESULTS: Köhne classification: good (54.2%), intermediate (26.8%), and poor prognosis (19%). 50.4% received irinotecan-based CT. Median number of cycles 6 with a total response rate of 38.9%. 23.2% stopped first-line CT due to toxicity. 50.7% suffered grade 3-4 toxicity: digestive (28.2%), hematologic (19.7%), and fatigue (25.4%). 7.7% episodes of neutropenic fever with 4.9% toxic deaths. 70.9% of grade 3-4 episodes occurred in the first four cycles. Median follow-up of 33.9 mo; median OS of 15.9 mo. For Köhne classification: good (20 mo), intermediate (15.8 mo), and poor (6.8 mo). Toxicity analysis: female sex and age > 70 yr predicted higher overall grade 3-4 toxicity, with no differences in CT efficacy; age > 70 yr and PS > 1 predicted higher grade 3-4 fatigue. No relationship could be found between baseline laboratory characteristics and higher toxicity, except baseline hemoglobin and grade 3-4 hematologic toxicity. CONCLUSIONS: Female and elderly patients have a higher grade 3-4 toxicity rate when treated with combination CT with oxaliplatin or irinotecan. Prognostic classifications such as Köhne's can help differentiate subgroups of patients who benefit little with the use of combination CT.

Analysis of prognostic factors and applicability of Kohne's prognostic groups in patients with metastatic colorectal cancer treated with first-line irinotecan or oxaliplatin-based chemotherapy.

BACKGROUND: The objective of this study was to analyze prognostic factors for survival and to assess the applicability of Kohne's classification in patients treated with irinotecan- or oxaliplatin-based first-line chemotherapy. PATIENTS AND METHODS: One hundred forty-two consecutive cases from a single center were retrospectively reviewed. Median patient age was 62 years. Sixty percent were men. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0/1 in 88%. Primary tumor resection (PTR) was performed in 80.6% of patients who initially had stage IV disease. Chemotherapy consisted of fluoropyrimidines or raltitrexed plus irinotecan (50.5%), oxaliplatin (38.5%), or both (11%). Univariate and multivariate analyses for survival were performed using pretreatment patient characteristics. RESULTS: Median follow-up was 33.9 months and median overall survival was 15.9 months. Significantly unfavorable prognostic factors were PTR not being performed, disease involvement of >1 organ, liver metastases, undifferentiated histology, EGOG PS>1, increased serum carcinoembryonic antigen and cancer antigen 19.9 levels, hypoalbuminemia, leucocytosis, and elevated alkaline phosphatase and lactate dehydrogenase (LDH) levels. Only ECOG PS, PTR, increased LDH level, no hypoalbuminemia, and number of organs involved retained prognostic value in the multivariate analysis. The incidence and median survival for Kohne's prognostic groups were as follows: good (54.2%; 20 months), intermediate (26.8%; 15.7 months), and poor (19%; 6.8 months). For patients with stage IV disease at presentation, PTR was associated with a significantly longer survival, mainly in patients with an ECOG PS of 0/1. CONCLUSION: Eastern Cooperative Oncology Group PS, PTR, serum albumin, increased LDH levels, and organ involvement were the main prognostic indicators in our series. Kohne's prognostic groups, developed in the era of 5-fluorouracil treatment, also seem to be applicable to patients treated with combination chemotherapy. Primary tumor resection should always be considered, especially in patients with an ECOG PS of 0/1. However, the benefit of PTR and multiple-agent chemotherapy is questionable in patients with an ECOG PS of >1.