Trastuzumab and thyroid dysfunction: An association to be aware of.

The incidence of autoimmune thyroid disorders is higher among women with breast cancer (BC) than in other solid malignancies, while it has not a prognostic impact. Trastuzumab (T) is a humanized monoclonal antibody approved for human epidermal growth factor receptor 2 (HER2)-positive BC in the neoadjuvant, adjuvant, and metastatic scenarios. Since 2014, subcutaneous (SC) T has been employed with the same efficacy as the intravenous formulation together with an easier way of administration. To date, autoimmune thyroiditis has been linked rarely to the use of intravenous T, and no cases have been related to the SC presentation. We report two cases of HER2-positive early BC patients who developed hypothyroidism during maintenance therapy with SC T that required levothyroxine supplementation. SC T includes recombinant human hyaluronidase to facilitate tissue penetration of the drug. This enzyme may alter the thyroid gland stroma and facilitate the development of thyroid disorders. Thyroid function tests are recommended in patients on SC T.

37th Annual San Antonio Breast Cancer Symposium. Resumen de las aportaciones translacionales y clínicas más relevantes / 37th Annual San Antonio Breast Cancer Symposium. Summary of the most important translational and clinical contributions

En diciembre de 2014 hemos tenido la oportunidad de ampliar nuestro conocimiento en el Simposio Internacional de Cáncer de Mama, celebrado en San Antonio, resaltando: 1) en el escenario básico, la adquisición de mutaciones durante el proceso de carcinogénesis y metástasis, aumentando la clonalidad y heterogeneidad tumoral, el papel pronóstico de los neoantígenos y los linfocitos infiltrantes en el residuo tumoral tras la neoadyuvancia, así como el mayor conocimiento de alteraciones en el receptor de estrógeno asociadas a hormonorresistencia; 2) en el translacional, el empleo de xenoinjertos derivados de tumores de pacientes en modelos murinos para evitar las resistencias terapéuticas, y los biomarcadores líquidos para descartar enfermedad mínima residual en cáncer de mama precoz; y 3) en clínica los resultados tanto en prevención como en adyuvancia con hormonoterapia, la quimioterapia en triples negativos y las novedades en inmunoterapia (AU)

The 37th San Antonio Breast Cancer Symposium, held in December 2014, provided an opportunity to gain greater knowledge. Notable contributions were the following: 1) in basic research, the acquisition of mutations in carcinogenesis and metastasis, which increase with clonality and heterogeneity; the prognostic role of neoantigens and infiltrating lymphocytes in the residual tumor after neoadjuvant chemotherapy; and an increased knowledge of molecular mutations in the estrogen receptor, which explain hormonal resistance; 2) in the translational arena, the role of patient-derived xenografts to avoid therapeutic resistance; and the role of liquid biomarkers to detect minimal residual disease in early breast cancer; and 3) in the clinical scenario, advances in prevention and hormone therapy, and news on triple-negative tumors and immunotherapy (AU)

Leptomeningeal carcinomatosis: prognostic value of clinical, cerebrospinal fluid, and neuroimaging features.

INTRODUCTION: Leptomeningeal carcinomatosis (LC) is a devastating complication occurring in 5% of all patients with cancer. To date there are no well-established prognostic markers in patients with LC, except for the presence of cerebrospinal fluid (CSF) blocks and the Karnofsky performance status scale (KPS). We aimed to identify clinical, neuroradiologic and CSF prognostic factors related to LC survival and to develop an easy-to-use Prognostic Scoring Scale (PSS) to identify patients who are more likely to benefit from receiving treatment. METHODS: Single-center retrospective study evaluating patients who had a diagnosis of LC during a 10-year period. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LC were also included. RESULTS: Fifty patients with LC were analyzed (58% women). Median age was 54.4 years, and KPS was 60%. The most common types of tumor were breast (35%), lung (24%), and hematologic malignancies (16%). Thirty-two percent of patients were diagnosed by imaging, 22% by cytology, and 40% by both. Median overall survival (OS) was 10 weeks (95% confidence interval 5.1-14.9). Median OS for patients who received specific treatment was 21.2 weeks vs. 6.38 weeks for patients receiving supportive care only (p<0.001). In multivariate analysis, initial KPS, initial CSF protein level (<112 mg/dL) and time from diagnosis of primary tumor to diagnosis of LC (>67 weeks) were significant and independent predictors of increased survival. CONCLUSIONS: Prognosis remains poor in LC. The predictive factors for patients with LC here identified could help to improve the selection of patients who are more likely to benefit from receiving treatment.

Sequential administration of dose-dense epirubicin/cyclophosphamide followed by docetaxel/capecitabine for patients with HER2-negative and locally advanced or node-positive breast cancer.

PURPOSE: Capecitabine is effective against metastatic breast cancer (MBC). We hypothesized that sequential treatment with dose-dense epirubicin/cyclophosphamide (EC) and docetaxel/capecitabine would be active and tolerable in the adjuvant/neoadjuvant setting. METHODS: In this prospective phase II clinical trial patients with HER2-negative and node-positive or locally advanced tumors were eligible to receive four cycles of EC (100/600 mg/m2) every 2 weeks with G-CSF on days 3-10, followed by four cycles of docetaxel/capecitabine (75/1,000 mg/m2 b.i.d., days 1-14) every 3 weeks. RESULTS: Fifty-five patients were enrolled with median age of 49, and 80% had hormone receptor-positive disease. The median tumor size was 2.5 cm, with a median of two axillary nodes involved. Seventy-five percent of the first 20 patients had grade 2/3 hand-foot syndrome (HFS). Dose reduction of capecitabine to 800 mg/m2 reduced the grade 2/3 HFS incidence to 31% in the remaining patients. No grade 4/5 toxicities were observed. All 20 patients treated preoperatively responded, with 5 (25%) pathologic complete responses and 3 additional pT0N1 tumors. At a median follow-up of 48 (range 28-60) months, the event-free and overall survival rates are 91 and 98%, respectively. CONCLUSIONS: Sequential treatment with dose-dense EC followed by docetaxel/capecitabine, using a lower capecitabine dose than that approved for MBC, has an acceptable toxicity profile and encouraging activity when used as neoadjuvant or adjuvant treatment of breast cancer.

Early breast cancer treated with conservative surgery, adjuvant chemotherapy, and delayed accelerated partial breast irradiation with high-dose-rate brachytherapy.

PURPOSE: To evaluate the feasibility and intermediate-term results of conservative surgery, adjuvant chemotherapy, and delayed accelerated partial breast irradiation (APBI) with high-dose-rate brachytherapy. METHODS AND MATERIALS: Between 2000 and 2007, a total of 26 patients with a median age of 54 years were treated with conservative surgery followed by adjuvant chemotherapy and exclusive high-dose-rate brachytherapy. Inclusion criteria followed the Radiation Therapy Oncology Group 95-17 trial guidelines. The tumor bed was marked at the time of surgery (n = 2) or before brachytherapy (n = 24). The brachytherapy procedure was performed at a median of 22 weeks after surgery. A median of 14 brachytherapy catheters were placed in three to four parallel planes. A dose of 34.0 Gy in 10 b.i.d. fractions given over 5 consecutive days was prescribed to the clinical target volume (CTV90). RESULTS: After a median followup of 53 months (range, 6.8-81), Radiation Therapy Oncology Group Grade 1-2 events and Grade 3 events were observed in 10 (38.4%) patients and 3 (11.5%) patients, respectively. No Grade 4-5 events were observed. Patients rated their cosmetic result as excellent (37.5%), good (50.0%), fair (8%), or poor (4%) based on the Wazer's Criteria. The 6-year actuarial local, elsewhere in the breast, and distant control rates were 100%, 96.2%, and 96.2%, respectively. Six-year disease-free survival and overall survival were 92.3% and 96.2%, respectively. CONCLUSIONS: Patients undergoing surgery and adjuvant chemotherapy can still be candidates for APBI. Optimal visualization of the internal lumpectomy scar before implantation is mandatory. Cosmetic results may be slightly worse due to the interaction between chemotherapy and APBI, and technical refinements may be needed in this group of patients.

Docetaxel administered during pregnancy for inflammatory breast carcinoma.

We report the case of a 35-year-old pregnant woman with inflammatory breast carcinoma initially treated with 5-fluorouracil/doxorubicin/cyclophosphamide beginning her 13th week of pregnancy. There was no noticeable shrinkage of the axillary or breast tumors after 4 cycles, at which point the patient accepted a treatment change to docetaxel. Four cycles of docetaxel at 100 mg/m2 every 21 days were delivered from the 25th week of pregnancy with good tolerance. She exhibited a clinical complete response, determined by clinical examination and imaging tests. Obstetric monitoring with fetal ultrasound showed normal fetal development throughout chemotherapy. After delivery of a healthy child, she underwent surgery, which showed tumor downstaging to pT0 N2, followed by radiation therapy and hormone therapy. This report suggests the safety of docetaxel after the first trimester of pregnancy.

Intraoperative radiotherapy electron boost followed by moderate doses of external beam radiotherapy in resected soft-tissue sarcoma of the extremities.

PURPOSE: To analyze the patterns of failure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). PATIENTS AND METHODS: Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was >5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. RESULTS: Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P=0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P=0.01). CONCLUSIONS: IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage.

Docetaxel plus vinorelbine as salvage chemotherapy in advanced breast cancer: a phase II study.

PRECIS: Administration of a combined regimen of docetaxel plus vinorelbine every 4 weeks is feasible and shows activity in heavily pretreated patients with advanced breast cancer. PURPOSE: To determine the activity and tolerance of docetaxel plus vinorelbine in heavily pretreated patients with advanced breast cancer. METHODS: Thirty-five metastatic breast cancer patients with ECOG performance status of 0-2 received docetaxel (80 mg/m2 given intravenously) on day 1 and vinorelbine (30 mg/m2 given intravenously) on days 1 and 14, every 4 weeks. The median number of prior chemotherapy regimens was 2 (range: 1-4). Twenty-five patients (71.4%) had been treated previously using intensive therapy approaches with peripheral blood-derived stem cell (PBSC) support, including high-dose chemotherapy (11 patients), multicyclic dose-intensive chemotherapy supported with repeated PBSC infusions (seven patients), or both (seven patients). Twenty-eight patients (80%) received previous chemotherapy for metastatic disease. Adjuvant therapy in the remaining seven patients consisted of high-dose chemotherapy and PBSC support or an anthracycline-containing regimen. RESULTS: The total number of courses was 229, and the median number of courses per patient was 6 (range: 1-16). There was one toxic death (2.8%). Grade 3-4 toxicities included mucositis (17.1%), neutropenia (37.1%), anemia (5.7%), vomiting (2.9%), and asthenia (14.3%). Eighteen patients (58%; 95% CI: 40.6-75.4%) achieved an objective response, including four complete responses (12.9%) and 14 partial responses (45.1%). Overall response rate was 51.4% (95% CI: 34.8-67.9%). After a median follow-up of 20 months (range: 2-42), overall survival was 20 months (95% CI: 16-24), and median time to progression was 13 months (95% CI: 7-19). CONCLUSION: This combination shows activity and an acceptable toxicity profile in patients with advanced breast cancer.

Irinotecan, oxaliplatin, and 5-fluorouracil/leucovorin combination chemotherapy in advanced colorectal carcinoma: a phase II study.

The purpose of this study was to evaluate the efficacy and tolerance of a combination of irinotecan, oxaliplatin, and 5-fluorouracil (5-FU)/leucovorin in advanced colorectal cancer (ACC). Twenty-six consecutive patients with ACC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of oxaliplatin (120 mg/m2 intravenously [i.v.] for 2 hours) on day 1, irinotecan (250 mg/m2 i.v. for 90 minutes) on day 1, and 5-FU (2600 mg/m2 plus leucovorin 500 mg/m2 i.v. in a 24-hour infusion) on day 1 and 15, every 4 weeks. Five of the patients (19.2%) had shown previous chemoresistance. One hundred sixty-two cycles were administered (median, 6; range, 3-13 cycles). All patients were evaluated for toxicity; 23 were evaluable for response. According to intention-to-treat, the overall response rate was 69.2% (18 patients; 95% CI: 48.2%-85.7%), including 3 complete remissions (11.5%). Four additional patients (15.3%) had stable disease, and only 1 (3.8%) progressed. Major toxicities were neutropenia and diarrhea. Grade 3 neutropenia occurred in 9 patients (34.6%), and grade 4 occurred in 1 patient (3.8%). Grade 3 diarrhea occurred in 8 patients (30.7%) and grade 4 in 1 patient (3.8%). Other toxicities were mild. After a median follow-up of 15.5 months, the median progression-free survival was 14 months. Seventeen patients (65.4%) are still alive, and the median overall survival has not been reached yet. This combination of irinotecan, oxaliplatin, and 5-FU/leucovorin is fairly well tolerated and shows promising activity in ACC. This treatment merits further comparison with other combination regimens.

Combined irinotecan, oxaliplatin and 5-fluorouracil in patients with advanced colorectal cancer. a feasibility pilot study.

OBJECTIVES: To evaluate the feasibility and a possible activity range of combination irinotecan (CPT-11), oxaliplatin, and 5-FU in advanced colorectal cancer (ACC). PATIENTS AND METHODS: A total of 53 patients (51% chemoresistant) were treated. Twenty-eight received monthly intravenous oxaliplatin (120 mg/m2) and CPT-11 (250 mg/m2) on day 1 and a course of 5-FU; these constituted the IRI250 group. Twenty-five received monthly intravenous oxaliplatin (120 mg/m2), CPT-11 (300 mg/m2) on day 1, and a course of 5-FU (IRI300 group). 5-FU administration was carried out as follows. Those with predominant hepatic disease (n = 32) received an intra-arterial infusion of 5-FU (2,500 mg/day on days 1-4); these were the IA-FU group. The remaining 21 patients received intravenous 5-FU (2,600 mg/m2 plus leucovorin 500 mg/m2 on days 1 and 15); these constituted the IV-FUFOL group. RESULTS: Intention-to-treat response rate was 54.7% (4 CR, 7.5%). Twelve patients (22.5%) had stable disease; only 4 (7.5%) progressed. Median progression-free and overall survivals were 10 and 18 months, respectively. One-year progression-free and overall survival rates were 44.3 and 67.4%, respectively. Grade 3-4 toxicities included diarrhea (45.3% of patients), neutropenia (52.8%), mucositis (13.2%), and emesis (11.3%). There were 3 treatment-related deaths (5.7%), all in the IA-FU/IRI300 subgroup. Severe adverse effects requiring chemotherapy dose adjustment were observed in 67.9% of the patients, with odds ratios 9.04-fold higher in the IA-FU/IRI300 group (95% CI: 1.07-76.20) and 0.23-fold lower in the IV-FUFOL/IRI250 group (95% CI: 0.05-0.97). CONCLUSION: This combination seems to have substantial activity in ACC. Overall toxicity was unacceptable in the IA-FU and IRI300 groups, with diarrhea and cytopenia constituting the dose-limiting side effects. Tolerance and efficacy profiles achieved with IV oxaliplatin (120 mg/m2 day 1), IV CPT-11 (250 mg/m2 day 1) and IV 5-FU 2.6 g/m2 with IV leucovorin (500 mg/m2 days 1 and 15) was favorable and deserves further investigation.

Tratamiento complementario con citostáticos en el sarcoma de partes blandas del adulto / Complementary treatment with cytostatics in sarcoma of soft tissues of adults

A pesar de los resultados atentadores en el control local de los SPB, el falto distal oscila entre un 27% y un 39%, y sólo un pequeño número de los pacientes que fallan puede ser curado con citostáticos, en diversas combinaciones. En esta revision se comentan estudios efectuados con citostáticos después del tratamiento local con cirugía asociada o no a radioterapia

Tratamiento complementario con citostáticos en el sarcoma de partes blandas del adulto / Complementary treatment with cytostatics in sarcoma of soft tissues of adults

A pesar de los resultados atentadores en el control local de los SPB, el falto distal oscila entre un 27% y un 39%, y sólo un pequeño número de los pacientes que fallan puede ser curado con citostáticos, en diversas combinaciones. En esta revision se comentan estudios efectuados con citostáticos después del tratamiento local con cirugía asociada o no a radioterapia (AU)