可手术乳腺癌术前全身治疗存在的问题及未来方向

乳腺癌术前全身治疗(preoperative systemic therapy,PST)也称为新辅助全身治疗,包括化疗、内分泌治疗和生物学靶向治疗,是乳腺癌综合治疗的重要组成部分.     

Presurgical systemic treatment of nonmetastatic breast cancer: facts and open questions

There are several advantages of administering primary systemic therapy (PST) instead of adjuvant therapy in the management of early breast cancer patients: (a) PST allows for a quantifiable evaluation of the sensitivity or resistance of any treated case and (b) the response assessment offers the opportunity to "cross over" to a different regimen for an individual patient, leading to more flexible, "tailored" therapies. Indeed, these advantages are tenable if one assumes that the primary tumor response serves as a surrogate marker of the efficacy of PST in terms of survival. Unfortunately, this has not yet been validated. The data that are actually available show that both clinical complete response (cCR) and pathological (p)CR have prognostic significance. pCR after chemotherapy has a greater prognostic impact than cCR; however, it is frequently observed in a subset of tumors-such as those that are estrogen receptor negative, are human epidermal growth factor receptor positive, and have elevated proliferative activity-but occurs rarely in their human epidermal growth factor receptor-2/neu counterparts. cCR is more sensitive than pCR, but its assessment presents many hindrances. cCR after chemotherapy can predict early on which tumors are destined to undergo pCR, suggesting a role for this endpoint guiding further treatment decisions early on. The pCR rate in small randomized PST studies comparing chemotherapy with chemotherapy plus trastuzumab was able to predict the difference in survival observed in large, randomized adjuvant trials with a similar study design. Conversely pCR cannot predict the outcome benefit of patients undergoing different hormonal therapies. In conclusion, pCR may be a reliable surrogate endpoint for PST efficacy in a subset of patients undergoing chemotherapy.     

Palliative care needs in a District General Hospital: a survey of patients with cancer

Although sophisticated treatment of cancer requires the resources of specialist cancer treatment centres, most patients with cancer still undergo initial diagnostic investigation and treatment in district general hospitals (DGHs). The DGH frequently remains the principle site of referral for management of symptoms and terminal care. This survey was carried out at a DGH which has no palliative care services. It aimed to demonstrate the need for such services by collecting data on inpatients with cancer and interviewing members of the nursing staff. Of 63 patients studied, 76% were admitted as emergencies, 50% had newly diagnosed cancer and 27% died in hospital. The majority (85%) were cared for on general medical, surgical and care of the elderly wards. Assessment of patients' symptoms suggested thet 39 (62%) might have benefited from the services of a palliative care team. Interviews with nursing staff highlighted the need for improved communication between professionals, increased staff education and support, and highlighted the particular difficulties that exist in caring for patients with advanced cancer and their families on busy acute general hospital wards. Imaginative and flexible approaches to the design and delivery of palliative services are essential if patients with cancer in DGHs are to receive the highest standards of care at all stages of their illness.     

Estimates of the world-wide prevalence of cancer for 25 sites in the adult population.

In health services planning, in addition to the basic measures of disease occurrence incidence and mortality, other indexes expressing the demand of care are also required to develop strategies for service provision. One of these is prevalence of the disease, which measures the absolute number, and relative proportion in the population, of individuals affected by the disease and that require some form of medical attention. For most cancer sites, cases surviving 5 years from diagnosis experience thereafter the same survival as the general population, so most of the workload is therefore due to medical acts within these first 5 years. This article reports world-wide estimates of 1-, 2-3- and 4-5-year point prevalence in 1990 in the population aged 15 years or over, and hence describes the number of cancer cases diagnosed between 1986 and 1990 who were still alive at the end of 1990. These estimates of prevalence at 1, 2-3 and 4-5 years are applicable to the evaluation of initial treatment, clinical follow-up and point of cure, respectively, for the majority of cancers. We describe the computational procedure and data sources utilised to obtain these figures and compare them with data published by 2 cancer registries. The highest prevalence of cancer is in North America with 1.5% of the population affected and diagnosed in the previous 5 years (about 0.5% of the population in years 4-5 and 2-3 of follow-up and 0.4% within the first year of diagnosis). This corresponds to over 3.2 million individuals. Western Europe and Australia and New Zealand show very similar percentages with 1.2% and 1.1% of the population affected (about 3.9 and 0.2 million cases respectively). Japan and Eastern Europe form the next batch with 1.0% and 0.7%, followed by Latin America and the Caribbean (overall prevalence of 0.4%), and all remaining regions are around 0.2%. Cancer prevalence in developed countries is very similar in men and women, 1.1% of the sex-specific population, while in developing countries the prevalence is some 25% greater in women than men, reflecting a preponderance of cancer sites with poor survival such as liver, oesophagus and stomach in males. The magnitude of disease incidence is the primary determinant of crude prevalence of cases diagnosed within 1 year so that differences by region mainly reflect variation in risk. In the long-term period however different demographic patterns with long-life expectancy in high-income countries determine a higher prevalence in these areas even for relatively uncommon cancer sites such as the cervix.     

Evaluation of prognostic factors and comparison of systemic treatment modalities in patients with recurrent or metastatic endometrial carcinoma

Background Prognostic factors related to survival in patients with inoperable metastatic or recurrent endometrial carcinoma (MREC) have remained unclear due to lack of clinical trials. The management of these patients is also controversial. This study was performed to compare the efficacy and toxicity profiles of two different systemic therapies (chemotherapy vs hormonal therapy) given for the treatment of patients with MREC and to identify the impact of various prognostic factors on the survival. Methods Between 1992 and 2004, 44 patients with MREC were admitted to our oncology department. Four cases were excluded from this retrospective study because of lack of data in their charts. Age, presence of other systemic diseases (such as diabetes mellitus, hypertension), histological type, tumor grade, stage, disease-free interval, site of recurrence or metastasis, systemic treatment modality, overall response to treatment, and duration of time to progression were evaluated as prognostic factors. Cox regression analysis was performed for identification of independent prognostic factors and differences between patients characteristics of two treatment groups were calculated by the chi-square or t test. Results The median follow-up was 18 mo (range 3–113). The overall response rates for chemotherapy and hormonal therapy group were 42% and 41%, respectively (p>0.05). The median time to progression was 4 mo for the chemotherapy group and 5 mo for the hormonal therapy group (P>0.05). The median survival after metastasis or recurrence was 11 mo for the chemotherapy group and 16 mo for the hormonal therapy group (p>0.05). In the group of chemotherapy, grade 3–4 hematologic and nonhematologic toxicities were seen in eight and two, patients, respectively. No grade 3–4 toxicities were noted in patients treated with hormonal therapy. In multivariate analysis, only time to progression (p=0.001) and grade (p=0.04) were the independent prognostic factors on survival after metastasis or recurrence. Conclusion Histological differentiation and duration of time to progression are predictive factors for survival after metastasis or recurrence in the whole group. The efficacy of two different groups of treatment in these patients appears to be similar. But the chemotherapy may have some disadvantageous in terms of toxicity. This study supports a future randomized prospective trial of hormonal therapy vs chemotherapy in patients with MREC.     

Understanding and addressing social determinants to advance cancer health equity in the United States: A blueprint for practice,research, and policy

Although cancer mortality rates declined in the United States in recent decades, some populations experienced little benefit from advances in cancer prevention, early detection, treatment, and survivorship care. In fact, some cancer disparities between populations of low and high socioeconomic status widened during this period. Many potentially preventable cancer deaths continue to occur, and disadvantaged populations bear a disproportionate burden. Reducing the burden of cancer and eliminating cancer-related disparities will require more focused and coordinated action across multiple sectors and in partnership with communities. This article, part of the American Cancer Society's Cancer Control Blueprint series, introduces a framework for understanding and addressing social determinants to advance cancer health equity and presents actionable recommendations for practice, research, and policy. The article aims to accelerate progress toward eliminating disparities in cancer and achieving health equity.     

Public policy, human consequences: the gap between biomedicine and psychosocial reality

Despite evidence-based research demonstrating the high prevalence rates of emotional distress, medical systems continue to focus their attention on biomedical aspects of treatment leaving a significant gap in patient care. This paper reflects on values and policy and suggests that we are unlikely to change health care systems unless we routinely address comprehensive aspects of the patient's experience. If we do not measure indicators of emotional distress, we risk not responding to this significant aspect of the cancer experience. The key message to health care providers here is: what we measure is what we act upon.     

Advances in the systemic treatment of pancreatic neuroendocrine tumors

Constituting about 1-2% of all tumors of the pancreas, pancreatic neuroendocrine tumors (PNETs) are a subgroup of gastroenetropancreatic neuroendocrine tumors (GEP-NETs) with distinct tumor genetics, biology, and clinicopathological features. Surgical resection is amenable only in a minority of the cases so systemic therapies are considered in most of them. The goals of medical treatment are to control the associated symptoms and signs of the specific tumors and to shrink the tumor mass. Somatostatin analogues can, not only decrease the secretion of peptides and inhibit their functions but also stop tumor growth. Other medical options for limiting tumor growth include interferon, systemic chemotherapy, and targeted therapies including, angiogenesis inhibitors, epidermal growth factor inhibitors, and mTOR inhibitors. Newer agents are tested and the treatment options expected to increase in the near future. Meanwhile optimal use of the available therapeutic strategies is critical.     

食管癌内科治疗及综合治疗进展

食管癌的综合治疗已日益受到临床的重视,放疗、化疗、手术三者的结合是食管癌综合治疗的趋势,合理而有效的综合治疗,已取得较单一方法更为满意的疗效,提高了患者的长期生存率。新的化疗药物的应用、对新辅助化疗的认识、和对辅助性化疗的再认识是食管癌内科治疗领域近年来发展的亮点。本文综述了近年来相关重要文献和临床试验,对食管癌的内科治疗和综合治疗进展作一介绍和述评,尤其是在疗效、生存率和不良反应等方面。     

卵巢癌的初始治疗

 卵巢癌的首次治疗直接关系患者预后。早期卵巢癌（EOC）手术效果良好,化疗似无必要。但对高危EOC患者,术后化疗是有意义的。对于晚期患者,理想的细胞减灭术是治疗的基石。术前估计不能达到理想减灭术者,应先行新辅助化疗,然后再手术。卡铂和紫杉醇联合化疗已成为卵巢癌化疗的首选方案。     

Historical perspective and advances in the treatment of multiple myeloma

Corticosteroids and melphalan were used for decades to treat multiple myeloma. Combination chemotherapy has been extensively studied with similar overall survival rates to melphalan and prednisone. In the last decade, the development of new agents has progressed significantly. Thalidomide and its newer derivatives lenalidomide, bortezomib, and pegylated liposomal doxorubicin have drastically revolutionized treatment approaches. As a result, numerous clinical trials have yielded exciting treatment strategies resulting in therapeutic advances, and improved responses and overall survival of patients. This review summarizes the international uniform response criteria for multiple myeloma and gives a historical perspective on previous therapies with updates on the newest available treatments.     

宫颈癌辅助性化疗的探讨

自1989年5月至1996年1月采用改良VBP方案作为宫颈局部肿瘤是巨块型（＞4cm）宫颈癌病例的第一线治疗共48人，142个疗程，无致命性毒性反应，获得了85％以上的有效率，完全缓解达45％，使48例原本只能放疗的患者有41例得以手术根治，而且手术切缘无残瘤。手术标本的病理学评价Ⅲ,Ⅳ级者占鳞癌病例的54％，占临床反应者的63％。淋巴结阳性率为12．1％。辅助化疗组5年生存率79.1％，对照组仅50.8％（P＜0.005）。     

Advances and controversies in the diagnosis, pathogenesis, and treatment of systemic mastocytosis

The term systemic mastocytosis (SM) encompasses a group of hematopoietic malignancies characterized by excessive proliferation of neoplastic mast cells that accumulate in the bone marrow and visceral organs. Most patients with SM, particularly those who present with aggressive clinical courses, carry somatic mutations of the v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) gene. KIT mutations are considered central events in the pathogenesis of SM and serve as diagnostic markers and putative therapeutic targets. The heterogeneity in the clinical course of patients with SM and recent advances in the genetic and immunophenotypic characterization of neoplastic mast cells may help to improve current diagnostic, taxonomic, and therapeutic approaches in SM.     

Equitably improving outcomes for cancer survivors and supporting caregivers: A blueprint for care delivery,research, education,and policy

Cancer care delivery is being shaped by growing numbers of cancer survivors coupled with provider shortages, rising costs of primary treatment and follow-up care, significant survivorship health disparities, increased reliance on informal caregivers, and the transition to value-based care. These factors create a compelling need to provide coordinated, comprehensive, personalized care for cancer survivors in ways that meet survivors’ and caregivers’ unique needs while minimizing the impact of provider shortages and controlling costs for health care systems, survivors, and families. The authors reviewed research identifying and addressing the needs of cancer survivors and caregivers and used this synthesis to create a set of critical priorities for care delivery, research, education, and policy to equitably improve survivor outcomes and support caregivers. Efforts are needed in 3 priority areas: 1) implementing routine assessment of survivors’ needs and functioning and caregivers’ needs; 2) facilitating personalized, tailored, information and referrals from diagnosis onward for both survivors and caregivers, shifting services from point of care to point of need wherever possible; and 3) disseminating and supporting the implementation of new care methods and interventions.     

Cardiovascular effects of systemic cancer treatment

Many methods of systemic anticancer treatment have detrimental effects on the cardiovascular system, thus limiting the possibility of further therapy, worsening patients’ quality of life and increasing mortality. The best recognized and most clinically relevant is the cardiotoxicity of anthracyclines. Other cytotoxic drugs associated with significant risk of cardiovascular complications include alkylating agents, 5-fluorouracil and paclitaxel. Cardiovascular adverse effects are also associated with the use of targeted therapies, such as trastuzumab, bevacizumab and tyrosine kinase inhibitors, and some of the drugs used in the treatment of hematological malignancies, such as all-trans-retinoic acid and arsenic trioxide.The most serious cardiac complication of anticancer therapy is congestive heart failure, associated predominantly with the use of anthracyclines, trastuzumab and high-dose cyclophosphamide. Myocardial ischemia is mainly caused by antimetabolite and interferon alpha treatment. Other adverse effects may include hypotension, hypertension, arrhythmias and conduction disorders, edema, pericarditis and thrombo-embolic complications.The aim of this review is to summarize and critically analyze the available evidence on the cardiovascular toxicity of systemic anticancer therapies, with particular attention to the recently recognized adverse effects of targeted therapies.     

A catalogue of treatment and technologies for malignant pleural mesothelioma

Malignant pleural mesothelioma is an aggressive fatal malignancy with a prognosis that has not significantly improved in the last decades. This review summarizes the current state of treatment and the various attempts that are made to improve overall survival for patients with malignant pleural mesothelioma. It also discusses technologies and protocols to test new and hopefully more effective compounds in a more individualized manner. These developments are expected to improve the prognosis for this group of patients.