Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes.

BACKGROUND: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. METHODS: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC). RESULTS: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). CONCLUSION: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.

Clinical outcomes to pemetrexed-based versus non-pemetrexed-based platinum doublets in patients with KRAS-mutant advanced non-squamous non-small cell lung cancer.

PURPOSE: KRAS mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether KRAS mutation correlates to increased sensitivity to pemetrexed in patients with advanced NSCLC is unknown. METHODS: Patients with advanced non-squamous NSCLC who had a documented EGFR and ALK WT genotype with simultaneous KRAS mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to KRAS mutation status. RESULTS: Of 356 patients identified, 138 harbored a KRAS mutation. Among KRAS-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%, P = 0.05), DCR (51.8% versus 71.9%, P = 0.02) and shorter median progression-free survival [mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03-2.12), P = 0.03] and median overall survival [mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27-2.94), P = 0.002] compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between KRAS WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death [HR 2.27 (95% CI 1.12-4.63), P = 0.02] among KRAS-mutant patients in multivariate analysis. CONCLUSION: Patients with KRAS-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether KRAS-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.

Economic evaluation of sunitinib versus pazopanib and best supportive care for the treatment of metastatic renal cell carcinoma in Chile: cost-effectiveness analysis and a mixed treatment comparison.

Background: Sunitinib and Pazopanib are two metastatic renal cell carcinoma (MRCC) treatment alternatives, however the health system in Chile does not consider coverage for any. The cost-effectiveness versus relevant comparator was assessed to support evidence-based decision making. Methods: A four health states Markov model was built: first, second line treatments, BSC and death. Benefits were measured in QALYs, and efficacy estimates were obtained from an indirect treatment comparison. A 10-year time horizon and a 3% undifferentiated discount rate were considered. Deterministic and probabilistic sensitivity analyses were performed. Results: The costs of treating MRCC with Sunitinib were higher than Pazopanib and BSC. When comparing Sunitinib versus Pazopanib, the incremental benefit is small favoring Sunitinib (0.03 QALYs). The base case scenario shows an average ICER of PA versus BSC of US$62,327.11/QALY and of US$85,885/QALY for Sunitinib versus Pazopanib. The ICER was most sensitive to the OS relative to BSC, where evidence was associated to important bias. Conclusions: Sunitinib or Pazopanib can be considered cost-effective if a 3 GDP per-capita threshold is assumed. The decision between SU or PA is highly sensitive to the price of the drugs, rather than the outcomes. Therefore, the decision might be made based on cost-minimization exercise.

Estudio de impacto presupuestal de Daclatasvir asociado a Asunaprevir desde la perspectiva del sistema de salud público chileno.

OBJECTIVES: To assess the impact on the 2015 national health budget of incorporating Daclatasvir/Asunaprevir (DCV / ASV) for the treatment of Hepatitis C genotype 1b (HC1b) in Chile. METHODS: A Chilean HC1b patients cohort was modelled using local prevalence and incidence data. Two scenarios were built and compared, one were all patients receive Peginterferon/Ribavirin (PR) and another were all patients are treated with DCV/ASV. The analysis was conducted from the perspective of public health system of Chile assuming 100% reimbursement and a time horizon of 5 years. Costs associated with drug treatment, adverse events, other relevant resources and costs associated with disease complications were used. RESULTS: At a total DCV/ASV treatment price of USD $55,039, an additional of USD $65,6MM are required during the first year (prevalent cases) equivalent to 0.71% of the 2015 national health budget. From year 2 (incident cases), an additional of USD $12,3MM are needed (0.13% of the 2015 health budget). A price reduction of 33% (USD $36,693), requires an additional of USD $38,2MM the first year and USD $7,16MM from the second year (0.11% and 0.6% of the health budget). If the treatment price is reduced further (USD $18,347), an additional USD $10,9MM are required for the first year and USD $2,03MM from the second year (0.3% and 0.057% of the 2015 heath budget). CONCLUSION: The impact on the health budget ranges between 0.3% and 0.71% the first year and decreases to less than 0.15% from the second year considering the price assessed price range.

Pacientes adultos com leucemia aguda - experiência da Faculdade de Medicina do ABC / Adult patients with acute leukemia - ABC Medical School experience

Introdução: Houve uma melhora lenta, porém definitiva no tratamento das leucemias agudas nos últimos anos. No entanto, existem controvérsias para pacientes com características específicas. Este trabalho tem como objetivo descrever o perfil epidemiológico dos pacientes com leucemia aguda atendidos no Hospital Estadual Mário Covas (HEMC), assim como demonstrar as curvas de sobrevida global e livre de doença e as taxas de mortalidade desta população. Métodos: Realizado estudo de corte transversal para avaliação de pacientes com diagnóstico de leucemias agudas da FMABC atendidos, no HEMC, no período de 2008 a 2012. Análise estatística das curvas de sobrevida utilizando Kaplan-Meier (XL Stat® v2012). Resultados: LMA: 50 pacientes com média de 57,72 anos de idade (18 a 89 anos), predomínio do sexo feminino 2,12: 1 e SLD = SG = 42 meses (média de seguimento = 49,9 meses); sendo 12 pacientes com LMA-M3 (SG=SLD=50%) e 38 outros subtipos (SG=SLD=39,5%). LLA: 17 pacientes, com média de 33,7 anos de idade (19 a 66 anos), predomínio do sexo masculino 1,43: 1 e SG = 58,82%, SLD = 47,3% (média de seguimento = 24,6 meses). Conclusão: Pacientes com LMA que atingem resposta na fase de indução apresentam curvas de SG e SLD compatíveis com a literatura. Pacientes com LLA apresentam SG e SLD inferior ao observado na literatura. É preciso prosseguir com este programa a fim de determinar o melhor tratamento para estes pacientes e o impacto do TCTH, assim como sua viabilidade.

Physician, patient and family attitudes regarding information on prognosis: a Brazilian survey.

BACKGROUND: Communication between physicians and patients is a fundamental aspect of cancer care, yet most physicians' perceptions are often inconsistent with the patients' stated preferences while prognostic information is the most misunderstood. PATIENTS AND METHODS: Members of the Brazilian Society of Oncology Physicians (n=609) were identified and asked to complete a mailed questionnaire. Outpatients (n=150) and their family members (n=150), oncologists and fellows (n=55) from a public healthcare hospital and a tertiary cancer hospital in Sao Paulo were also personally invited to participate. RESULTS: A total of 202 physicians, 150 outpatients and 150 family members were participated. The majority of patients (92%) believe they should know about their terminal stage compared with 79.2% of physicians and 74.7% of families (P=0.0003). Cancer patients were most likely to support disclosure of diagnosis and terminality (P=0.001), to consider that this disclosure was not stressful (P<0.0001) and that this knowledge would improve their quality of life (P<0.0001). CONCLUSIONS: Cancer patients seen in these centers in Southeastern Brazil prefer to know the truth about their poor prognosis more than their physicians and families think. Further studies with larger samples of patients and physicians are necessary to show if our results are representative of all Brazilian situations.

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis.

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P = 0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT = 14.9 and NNT = 2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18 ± 3.38% and 2.35 ± 1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

[Androgen deprivation therapy and morbid obesity: do they share cardiovascular risk through metabolic syndrome?]. / Terapia de privación de andrógenos y obesidad mórbida: ¿tienenen común el riesgo cardiovascular por síndrome metabólico?

BACKGROUND: Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. OBJECTIVES: Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. METHODS: This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. RESULTS: Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p=0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p=0.054). CONCLUSION: This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.

Doctor, how long?

This study aimed to quantify the average survival time of cancer patients once terminal sedation was started until death and identify potential variables that may influence their survival time on sedation. This is a retrospective cohort analysis of all consecutive terminal cancer patients who died after starting terminal sedation at public tertiary Brazilian Hospital. A total of 532 cancer patients died in Hospital Estadual Mário Covas during this period and 181 out of them who received terminal sedation were included in this analysis. The median survival was 27 h. By multivariate analysis, increase in the dose of sedative drug during sedation (odds ratio 1.576, 95% CI 1.113-2.232), use of opioids alone for sedation (odds ratio 1.438, 95% CI 1.046-1.977) and dyspnoea as cause of sedation (odds ratio 1.564 95% CI 1.045-2.341) were independent risk factors for a shorter survival time after starting terminal sedation. Sedated, terminal cancer patients usually live about 1 day. We identified risk factors for a shorter sedation period. This study is limited by its retrospective design and by the frequent use of opioids as the main sedative medications. Prospective studies must be carried out in order to validate these data.

Drug interactions in oncology: how common are they?

BACKGROUND: Drug-drug interactions (DDIs) comprise an important problem in medical oncology practice. We systematically reviewed the frequency of DDIs in oncology. METHODS: We searched PubMed for eligible articles and on-line databases for abstracts of major oncology meetings. RESULTS: Eight studies reported on the frequency of DDIs: six evaluated the frequency of potential DDIs, while two studies reported on real DDIs, i.e. interactions that had clinical consequences. Studies of potential DDIs found that approximately one-third of patients are exposed to dangerous drug doublets, with the most common ones involving warfarin and anticonvulsants. One study of real DDIs found that 2% of hospitalized cancer patients had a DDI as the cause of admission. CONCLUSIONS: Drug interactions comprise an important issue in oncology, with approximately one-third of ambulatory cancer patients being at risk of DDIs. Data are limited on the clinical consequences of drug interactions among cancer patients.

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy.

BACKGROUND: Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen after myelotoxic chemotherapy in breast cancer (BC) patients. METHODS: A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 microg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. RESULTS: The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen could be demonstrated. Toxicities were similar between XM02 and Neupogen. CONCLUSION: XM02 was superior to placebo and equivalent to Neupogen in reducing DSN after myelotoxic chemotherapy.

Burnout in cancer professionals: a systematic review and meta-analysis.

Burnout syndrome is typified by three dimensions: emotional exhaustion (EE), depersonalization (DP) and low personal accomplishment (PS), and is prevalent among cancer care providers. The objective is to conduct a systematic review and meta-analysis of studies that evaluated the presence of burnout syndrome in professionals dedicated to the care of cancer patients. A search was conducted of the MEDLINE, LILACS and COCHRANE databases. Articles were selected that had used the Maslach questionnaire to assess burnout syndrome prevalence, had evaluated at least 35 subjects (including physicians), had at least a 20% questionnaire response rate, and that were published in English, Spanish or Portuguese. Ten studies (2375 participants) were included in this analysis. Severe involvement by any one of the three dimensions ranged from 8% to 51%. The overall prevalence of EE was found to be 36% [95% confidence interval (CI) (31-41)], while for DP this was 34% [95% CI (30-39)] and for PS 25% [95% CI (0.16-34)], demonstrating considerable heterogeneity across studies. The prevalence of burnout syndrome is elevated among cancer professionals throughout the world but varies substantially among studies. Further research is needed to better understand and prevent this syndrome.

Bone and total alkaline phosphatase for screening skeletal metastasis in patients with solid tumours.

Alkaline phosphatase (AP) has several isoforms including bone alkaline phosphatase (BAP). We evaluated BAP and AP for screening for bone metastasis (BM) in patients with solid tumours. This is a prospective non-blinded study conducted at ABC Foundation School of Medicine Oncology clinics. A total of 40 subjects without a history of cancer and 62 patients with various solid tumours referred for a bone scan had serum drawn for BAP and AP determination. Bone alkaline phosphatase and AP levels in patients with cancer and BM, without BM and with no cancer, were 70.32 +/- 3.65 and 310.21 +/- 16.87 U/L; 41.40 +/- 2.80 and 113.23 +/- 12.95 U/L; 21.19 +/- 2.76 and 148.05 +/- 12.79 U/L respectively (P < 0.0001 for both AP and BAP). For BAP and AP sensitivity, specificity, positive and negative predictive values were 0.86 and 0.52; 0.69 and 1; 0.45 and 1; 0.94 and 0.87 respectively. ROC AUC value for BAP was 0.89 and for AP was 0.93. We conclude that BAP is more sensitive than AP, whereas AP had a remarkable specificity of 100%. In screening for BM in patients with solid tumours, obtaining initially BAP and then selecting for further investigation only patients with an abnormal AP may be a cost and resource saving strategy.

An open-label, fixed-dose study of bupropion effect on sexual function scores in women treated for breast cancer.

BACKGROUND: Sexual morbidity after chemotherapy and hormonal therapy for breast cancer can seriously affect patients' quality of life. Bupropion is an antidepressant that has been reported to increase libido. OBJECTIVE: To investigate the improvement of sexual function in female breast cancer patients using bupropion. PATIENTS AND METHODS: We performed an 8-week open trial using bupropion in women diagnosed with breast cancer who had received chemotherapy and were currently receiving adjunctive hormonal therapy. The Arizona Sexual Experience Scale (ASEX) was used. The ASEX scale includes five questions that evaluate sexual function in the following areas: libido, excitability and ability to reach orgasm. Women received oral Bupropion 150 mg/daily for 8 weeks and were evaluated prior to the initiation of the study and again during Weeks 4 and 8. RESULTS: Twenty patients were included in the study. At the beginning of the study, the mean ASEX score was 23.45 [21.67-25.24] 95% CI. After 4 weeks of treatment, we observed a reduction in the mean ASEX score that persisted until the end of the study, at eight weeks: 18.45 [16.59-20.31] 95% CI (P = 0.0003) and 18.95 [16.60-21.30] 95% CI (P = 0.0024), respectively. CONCLUSION: In this non-controlled open trial bupropion 150 mg/daily was associated with improved sexual function in women receiving adjuvant systemic treatment for breast cancer.

Use of complementary and alternative medicine by Brazilian oncologists.

Complementary and alternative medicine (CAM) is frequently employed by patients with cancer. An extensive survey was conducted among Brazilian cancer physicians to understand their attitude towards CAM. A questionnaire was sent to all 655 members of the Brazilian Cancer Society asking what is their opinion regarding CAM and if they would prescribe any CAM modality for their patients. They were also questioned regarding their degree of awareness of CAM self-administration by their patients. Overall, 119 questionnaires were returned to us (18%). Most oncologists knew at least one type of CAM (96.6%) and 76.7% had previously made use of at least one type of CAM for themselves. We observed that 76 (63.8%) of the oncologists used to ask their patients about CAM utilization and 37.8% described at least one reason to stimulate its use (68.8% as complementary treatment). Only 10% of the oncologists would prescribe at least one type of CAM and this attitude correlated significantly with previous physicians' use of CAM and with being a clinical oncologist as well as with having questioned patients about CAM use. Most oncologists (80.7%) would not indicate the use of CAM, mainly for lack of scientific proof of its efficacy (56.2%). Physicians knew many kinds of CAM and had frequently used some of them themselves, but only a minority of Brazilian oncologists would indicate them. As CAM use is very prevalent in our population, we believe that most of its utilization depends, probably, on patient's own and independent initiatives. However, these results should be viewed with caution because of the low response rate we observed in this study.

Randomized crossover trial of intravenous 5-FU versus oral UFT both modulated by leucovorin: a one-centre experience.

Although intravenous (IV) 5-fluorouracil (5-FU) and uracil/futraful (UFT) have comparable antitumour efficacy in the treatment of metastatic colorectal cancer (MCC), we wanted to assess which of these two regimens would be preferred by our patients. We randomized 20 previously untreated patients with MCC at our centre to receive oral UFT or bolus IV 5-FU both associated with leucovorin. After the first cycle patients were crossed over to the other arm. Before the third cycle we left patients to choose one of the regimens to continue their treatment until disease progression. Two patients chose 5-FU and 18 chose UFT (P < 0.001). Fewer side effects (50%) and convenience of home treatment (40%) were the main reasons for their choice for the oral regimen. UFT induced less mucositis (P = 0. 02) and diarrhoea (P = 0. 01). We conclude that convenience and lower toxicity may explain the observed preference for oral UFT.

Apert syndrome: analysis of associated brain malformations and conformational changes determined by surgical treatment.

Apert Syndrome, also called acrocephalosyndactylia type 1, is characterized by craniostenosis with early fusion of sutures of the vault and/or cranial base, associated to mid-face hypoplasia, symmetric syndactylia of the hands and feet and other systemic malformations. CNS malformations and intracranial hypertension are frequently observed in these patients. Early surgical treatment aims to minimize the deleterious effects of intracranial hypertension. Fronto-orbital advancement, the usual surgical technique, increases the intracranial Volume and improves the disposition of encephalic structures previously deformed by a short skull. This study analyzes CNS alterations revealed by magnetic resonance in 18 patients presenting Apert Syndrome, and the conformational alterations in the encephalic structures after surgical treatment. The patients' age in February 2001 ranged from 14 to 322 Months (m=107). Image study included brain magnetic resonance showing ventricular enlargement in five cases (27.8%), corpus callosum hypoplasia in five cases (27.8%), septum pellucidum hypoplasia in five cases (27.8%), cavum vergae in two cases (11.1%) and, arachnoid cyst in the posterior fossa in two cases (11.1%). Absence of CNS alterations was noted in 44.4% of cases. A corpus callosum morphologic index was established by dividing its height by its length, which revealed values that ranged from 0.4409 to 1.0237. The values of this index were correlated to the occurrence or absence of surgical treatment (p=0.012; t=2.83). Data analysis allowed the conclusion that the corpus callosum morphologic measure quantified the conformational alterations of the cerebral structures determined by the surgical treatment.

CK-19 expression by RT-PCR in the peripheral blood of breast cancer patients correlates with response to chemotherapy.

BACKGROUND: The recent introduction of sensitive RT-PCR-based techniques for the detection of epithelial antigen expression, such as CK-19, in the peripheral blood and bone marrow of breast cancer patients may provide an opportunity to evaluate tumor response at the molecular level, even in the absence of measurable disease while patients are still receiving chemotherapy. METHODS: We studied serially collected blood samples of 53 patients with breast cancer before, during, and after adjuvant, neoadjuvant, and palliative chemotherapy to evaluate its effects on the expression of CK-19 measured by RT-PCR. RESULTS: The percentage of CK-19 RT-PCR positivity decreased consistently from 43% (23/53) before chemotherapy to 14.3% (7/49), and to 18.9% (7/37) after 3 and 6 cycles, respectively (chi-square for linear trend = 7.948; p = 0.0048). Furthermore, there was a significant correlation between a negative CK-19 at three months and the response to chemotherapy (p = 0.024). CONCLUSION: We conclude that RT-PCR negativity for CK-19 expression at 3 months after the beginning of chemotherapy correlates with tumor response and, as treatment progresses, there is a significant trend for the occurrence of more negative RT-PCR results. Further studies are needed to confirm if this technique can be useful to assess response to chemotherapy in patients without measurable disease and if negativation of CK-19 expression while on chemotherapy is of prognostic significance.