Treatment strategies for advanced and metastatic cancer in Europe

ESTRO members were surveyed by questionnaires regarding the management of three cases of advanced cancer and the organisation of cancer care in their centre. There were 278 replies from within Europe from a total of 21 countries and 231 centres. The cases were a 64-year-old man with brain metastases from a small cell carcinoma of the lung, a 64-year-old woman with bone metastases from carcinoma of the breast on tamoxifen and a 59-year-old man with a squamous cell carcinoma (NSCLC) of the bronchus and positive mediastinal lymph nodes. Over 90% of respondents replied that they would give radiotherapy in each of these cases. The median total doses were 30 Gy for the brain metastases, 30 Gy for the bony metastases and 56 Gy for the case of NSCLC. There was variation as to the perceived prognosis and appropriate aims of therapy, particularly for the case of NSCLC. The total dose and number of fractions of radiotherapy could be related to the perceived aims and expectations of treatment, e.g. those aiming to extend life gave significantly higher total doses of radiotherapy (p = 0.0001) and those aiming to relieve symptoms gave significantly lower total doses (p = 0.0001). Treatment for this case was described as "radical" by 53% of respondents and as "palliative" by 47% and the prognosis was estimated to be less than 12 months by 41% and 1-2 years by 44%. Those describing treatment as radical and estimating longer survival gave higher doses and more fractions than those treating palliatively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological differences between primary and metastatic breast cancer

BackgroundLittle is known about how the immune microenvironment of breast cancer evolves during disease progression.Patients and methodsWe compared tumor infiltrating lymphocyte (TIL) count, programmed death-ligand 1 (PD-L1) protein expression by immunohistochemistry and mRNA levels of 730 immune-related genes using Nanostring technology in primary and metastatic cancer samples.ResultsTIL counts and PD-L1 positivity were significantly lower in metastases. Immune cell metagenes corresponding to CD8, T-helper, T-reg, Cytotoxic T, Dendritic and Mastoid cells, and expression of 13 of 29 immuno-oncology therapeutic targets in clinical development including PD1, PD-L1, and CTLA4 were significantly lower in metastases. There was also coordinated down regulation of chemoattractant ligand/receptor pairs (CCL19/CCR7, CXCL9/CXCR3, IL15/IL15R), interferon regulated genes (STAT1, IRF-1,-4,-7, IFI-27,-35), granzyme/granulysin, MHC class I and immune proteasome (PSMB-8,-9,-10) expression in metastases. Immunotherapy response predictive signatures were also lower. The expression of macrophage markers (CD163, CCL2/CCR2, CSF1/CSFR1, CXCR4/CXCL12), protumorigenic toll-like receptor pathway genes (CD14/TLR-1,-2,-4,-5,-6/MyD88), HLA-E, ecto-nuclease CD73/NT5E and inhibitory complement receptors (CD-59,-55,-46) remained high in metastases and represent potential therapeutic targets.ConclusionsMetastatic breast cancers are immunologically more inert than the corresponding primary tumors but some immune-oncology targets and macrophage and angiogenesis signatures show preserved expression and suggest therapeutic combinations for clinical testing.     

晚期胃癌药物治疗策略和展望

目的:总结国内外晚期胃癌药物治疗的研究现状。方法:以胃癌和药物治疗为关键词,检索Medline和中国生物医学文献数据库1989-01-2009-09的相关文献,获得英文文献1809篇,中文文献131篇。纳入标准:1)晚期胃癌患者的化疗;2)晚期胃癌的靶向治疗。根据纳入标准,精选81篇全文文献,最后纳入分析34篇。结果:晚期胃癌的药物治疗基本上是姑息性的,患者接受治疗后仅能获得部分缓解,且持续时间有限。对于晚期胃癌患者,目前国际上仍然没有统一的标准化疗方案。多个靶向药物在胃癌治疗中的效果正在观察。结论:近年对晚期胃癌治疗药物及方案的研究主要集中于以下几个方面,1)改进已有的联合化疗方案;2)评价已有有效方案;3)新的化疗药物、靶向药物的应用。     

Explaining differences in attitude toward adjuvant chemotherapy between experienced and inexperienced breast cancer patients.

PURPOSE: Previous studies have shown that patients who have experienced adjuvant chemotherapy (experienced patients) have a more favorable attitude towards chemotherapy than those who have not (inexperienced patients). However, not much is known about the reasons underlying this difference. According to the Theory of Planned Behavior, the attitude towards a particular behavior (eg, accepting chemotherapy) is based on beliefs about the likelihood of outcomes of the behavior and the evaluations of these outcomes. We used this theory to explore in what way the beliefs of experienced patients differed from those of inexperienced patients. PATIENTS AND METHODS: A cross-sectional survey was undertaken among 719 patients who had been treated for early-stage breast cancer between 1998 and 2003. Patients were asked, first, to indicate the likelihood of six positive and six negative outcomes of undergoing chemotherapy and, second, to give their evaluation of these outcomes. RESULTS: Four hundred forty-six women filled in the questionnaire (response rate, 62%). As hypothesized, experienced patients (ie, patients who had been treated with adjuvant chemotherapy as part of their primary treatment plan) had a more positive attitude towards chemotherapy. Experienced patients provided higher likelihood estimates of treatment advantages, such as life prolongation. In addition, they evaluated the positive outcomes of chemotherapy more favorably. With regard to the negative outcomes of chemotherapy, few differences were observed between treatment groups. CONCLUSION: Experienced patients have more confidence in the positive outcomes of chemotherapy than inexperienced patients. This might be the result of a cognitive mechanism to justify the way in which patients were treated.     

Treatment of locally advanced and metastatic non-small cell lung cancer in the elderly

In locally advanced NSCLC, RT/CHT can be used in fit elderly patients. In cases in which CHT is prohibitive, RT can be used alone. Advanced IIIB stage may be treated with palliative RT or CHT, each given alone. In metastatic NSCLC, platinum-containing regimens are feasible when elderly patients have good renal/cardiac function, but a third-generation drug may be a viable option, the choice depending on its toxicity profile. Short-course, palliative RT given in addition to CHT may play an important role in the treatment of symptomatic intra- and extrathoracic disease. Many questions concerning the optimal treatment for elderly patients with NSCLC remain unanswered and more trials designed for the elderly are urgently needed in the future.     

Chemosensitivity differences between primary and metastatic lesions of clinical gastric cancer

An in vitro chemosensitivity test, the succinate dehydrogenase inhibition (SDI) test, was used to examine 16 pairs of samples obtained simultaneously from primary and metastatic lesions of clinical gastric cancer. Concerning the metastases, 11 were in the lymph nodes and five in the liver. The chemosensitivities of metastatic lesions against six anti-tumour drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), and 5-fluorouracil (5-FU), differed from those in the primary lesions, and there were no correlations of chemosensitivities between the primary and the metastatic lesions against these drugs, except for DDP. The lymph nodes were more sensitive to CQ, ADM, MMC, DDP, ACR and 5-FU, while the liver was less sensitive than the primary lesions to CQ, ADM, MMC, DDP, and ACR. Our findings indicate that in patients with lymph node metastasis, there is a sensitivity to anti-tumour drugs, while in cases of liver metastasis, drug treatment may be less effective. We propose that chemosensitivity testing should be done when attempting to design anti-tumour drugs.     

Chemotherapy for advanced, recurrent, and metastatic cervical cancer

When cervical cancer is beyond curative treatment with surgery or radiation therapy, the prognosis is poor and palliation is the primary objective. Early prospective studies identified cisplatin as an active drug for advanced, metastatic, or recurrent cervical cancer, and results with other platinum analogs seemed inferior to cisplatin. Several phase III trials have established the combination of cisplatin plus paclitaxel as standard therapy for comparison. Using pooled data from 3 Gynecologic Oncology Group (GOG) phase III studies, a predictive model was developed to better identify patients who are unlikely to respond to cisplatin-containing chemotherapy. The GOG is currently developing a phase III trial to investigate the impact of bevacizumab and a regimen containing topotecan instead of cisplatin in combination with paclitaxel chemotherapy and also to externally validate the predictive model. This study has the potential to radically change standard care for cervical cancer chemotherapy. Furthermore, if the predictive model is upheld, then patients with high risk factors for treatment failure may be directed to chemotherapy regimens that do not include cisplatin or to investigational trials.     

Treatment of advanced breast cancer: the good, the bad and the ugly.

Every year more than 1 million women are newly diagnosed withbreast cancer, and this figure will likely reach 1.5 millionwith the increased number of cases arising in developing countries[1]. Many of these patients will be offered adjuvant treatmentbased on consideration of disease responsiveness to specifictherapies [2], and almost half eventually will have local ordistant relapses.  Metastatic, or advanced, breast cancer is a chronic diseaserequiring specific strategies to control disease progressionand related symptoms. The treatment choice is often based onevidence obtained from trials designed to investigate therapy-relatedissues such as whether one treatment yields better responsesor longer time to progression. These trials frequently evaluatewhether a given treatment is effective in a selected group ofpatients, usually using measurable or evaluable disease to guidepatient selection and avoiding, for example, those with only     

Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States.

PURPOSE: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. METHODS: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. RESULTS: Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P =.01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P =.40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P =.28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P =.10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P =.01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10(-3)). In stage III disease, the rates were 30% and 54%, respectively (P =.03), and in stage IV disease they were 33% and 64% (P =.002). CONCLUSION: There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.     

Differences in the therapeutic strategies for lung cancer between Europe/United States and Japan

Lung cancer is a leading cause of malignancy-related death worldwide. Recently, therapeutic strategies for lung cancer have dramatically progressed, and attempts have been made to standardize the therapy for lung cancer. Because the disease prevalence and the susceptibility to the drugs differ with the circumstances, such as lifestyle, and genetic background, and ethnicity, the standard therapeutic strategies for lung cancer may differ with the individual country or region. Actually, the EGFR tyrosine kinase inhibitor, gefitinib, is well known to be significantly effective for oriental people, including Japanese, female, adenocarcinoma and never-smoker, suggesting an inherited difference. Here we describe not only the standard therapeutic strategies but also the difference in therapeutic strategies for lung cancer between Europe/United States and Japan.     

草酸铂和伊立替康、氟尿嘧啶联合方案治疗晚期肠癌

目的 :总结探讨草酸铂和伊立替康、氟尿嘧啶联合方案治疗晚期肠癌近期疗效及毒副反应。方法 :2 5例晚期肠癌 ,用草酸铂、伊立替康和氟尿嘧啶 亚叶酸联合方案静脉应用或动脉介入 静脉用药 ,治疗两周期评价疗效及相关症状改善 (DRSI)及毒副反应。结果 :经治疗动脉介入 静脉用药组 15例 ,CR 1例 ,PR 9例 ,有效率 6 6 .6 %。静脉用药组 10例 ,PR 4例 ,有效率 4 0 .0 % ,两组疗效无显著差异 (P >0 .0 5 )。总有效率为 5 6 .0 %。 18例相关症状改善 ,毒副反应可耐受 ,未见严重不可逆反应。结论 :草酸铂和伊立替康和氟尿嘧啶联合方案治疗晚期肠癌复发或转移患者 ,疗效明确 ,安全有效 ,毒副作用小 ,无叠加毒性 ,可明显改善患者症状 ,提高生存质量。     

Testicular cancer in Europe and the USA: survival still rising among older patients

BackgroundDespite high curability, some testicular cancer (TC) patient groups may have increased mortality. We provide a detailed age- and histology-specific comparison of population-based relative survival of TC patients in Europe and the USA.DesignUsing data from 12 European cancer registries and the USA Surveillance, Epidemiology and End Results 9 database, we report survival trends for patients diagnosed with testicular seminomas and nonseminomas between 1993–1997 and 2003–2007. Additionally, a model-based analysis was used to compare survival trends and relative excess risk (RER) of death between Europe and the USA adjusting for differences in age and histology.ResultsIn 2003–2007, the 5-year relative survival of patients with testicular seminoma was at least 98% among those aged <50 years, survival of patients with nonseminoma remained 3%–6% units lower.Despite improvements in the relative survival of nonseminoma patients aged ≥50 years by 13%–18% units, survival remained markedly lower than the survival of seminoma patients of the same age. Model-based analyses showed increased RERs for nonseminomas, older, and European patients.ConclusionsThere remains little room for survival improvement among testicular seminoma patients, especially for those aged <50 years. Older TC patients remain at increased risk of death, which seems mainly attributable to the lower survival among the nonseminoma patients.     

Targeted strategies in the treatment of metastatic colon cancer

Advances in the understanding of tumor biology have led to the identification of important cellular processes involved in the pathogenesis of colon cancer. Drugs that interfere with these critical pathways are known as targeted agents. The goal of these therapies is to selectively interrupt the signal transduction pathways responsible for tumor growth and survival. Some of these targeted agents have made important, albeit modest, contributions to the treatment of patients with metastatic colorectal cancer. However, the activity levels with the currently available targeted therapies are far lower than experts had hoped, and toxicities are often nontrivial. This article reviews the available therapies, the data that justify their use, and the challenges of optimizing targeted therapies through combinations with cytotoxic chemotherapies and other targeted agents. Finally, some newer drugs and strategies currently being tested in clinical trials are discussed.     

Surgical strategies in colorectal cancer metastatic to the liver

Surgical resection remains a milestone in the treatment of colorectal metastases to the liver. There is a distinct subset of patients who benefit from surgical resection in terms of longer survival or definitive cure. The main effort of the surgical oncological regards the safety of the procedure and the adequacy of the recommendation. Many studies, some of them including multivariate analysis, have shown the presence of prognostic determinants of long-term survival and prognostic indexes of the outcome after hepatectomy. It is now accepted that liver resection should be done when the complete excision of all demonstrable tumor with clear resection margins is feasible. Major contra-indication is represented by the presence of extra-hepatic intra-abdominal disease or of unresectable lung metastatic deposits. There is a wide literature indicating that in very selected patients liver reresection and multiorgan synchronous or metachronous resections are beneficial. The role of neoadjuvant chemotherapy and especially postoperative adjuvant local (intra-hepatic) and systemic chemotherapy is promising and supported by recent multicenter randomised clinical trials.