What do we know about survivorship after treatment for extremity sarcoma? A systematic review

Objective

The varied presentations and treatments of extremity bone and soft tissue sarcoma mean that the issues faced by survivors are diverse and complex. The aim of this systematic review was to investigate what is known about this topic with a view to identifying areas for further research or service development.

Methods

This was a review of the English language literature identified from Medline and Ovid and hand searches published between January 2000 and September 2012. Results were compiled according to physical, psychological and social domains of survivorship.

Results

Of 182 studies identified, 22 met the inclusion criteria. There is a wide range of outcome measures used and a need for more objective measures. Unsurprisingly, survivors of extremity sarcoma typically demonstrate lower levels of physical functioning than healthy controls. In addition, survivors demonstrate a substantial psychological morbidity.

Conclusions

Services for survivors of extremity sarcoma should include rehabilitation and psychological support, sexual health services, expert pain management, and support to return to work.     

Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand?

Aim

Since the introduction of chemotherapy, survival in localised high-grade osteosarcoma has improved considerably. However, there is still no worldwide consensus on a standard chemotherapy approach. In this systematic review evidence for effectiveness of each single drug and the role of response guided salvage treatment of adjuvant chemotherapy are addressed, whereas in a meta-analysis the number of drugs in current protocols is considered.

Methods

A systematic literature search for clinical studies in localised high-grade osteosarcoma was undertaken, including both randomised and non-randomised trials. Historical clinical studies from the pre-chemotherapy era were included for comparison purposes.

Results

Nine historical studies showed a long-term survival of 16% after only local treatment. Fifty single agent phase II studies showed high response rates for adriamycin (A, 43%), ifosfamide (Ifo, 33%), methotrexate (M, 32%), cisplatin (P, 26%) but only 4% for etposide (E). In 19 neo-adjuvant studies the mean 5-year event free survival (EFS) was 48% for 2-drug regimens and 58% for ?3 drug regimens, with a 5-year overall survival (OAS) of 62% and 70%, respectively. Meta-analysis showed that ?3 drug regimens including methotrexate plus adriamycin plus cisplatin (plus ifosfamide) (MAP(Ifo)) had significant better outcome (EFS: HR = 0.701 (95% confidence interval [95% CI]: 0.615–0.799); OAS: HR = 0.792 (95% CI: 0.677–0.926) than 2-drug regimens, but there was no significant difference between MAP and MAPIfo (or plus etoposide). Salvage of poor responders by changing drugs, or intensifying treatment postoperatively has not proven to be useful in this analysis.

Conclusion

Meta-analysis in patients with localised high-grade osteosarcoma shows that 3-drug regimens, for example MAP are the most efficacious drug regimens.     

Postoperative radiation therapy for lung cancer: where do we stand?

Lung cancer is the leading cause of cancer mortality in the United States. Local recurrence after surgery for operable disease has long been recognized as a hindrance to long-term survival. Postoperative radiation therapy was logically explored as a means to improve local control and survival. Multiple randomized trials were conducted, many showing improved local control, but none demonstrated a statistically significant survival benefit. In fact, a meta-analysis showed a rather large survival detriment, presumably from treatment-related complications. Radiation therapy has evolved over the years, and more modern treatment planning and delivery has the potential to treat sites deemed at high risk of recurrence while limiting the dose to critical intrathoracic structures, which should decrease the risk of treatment-related complications. Recent studies have supported this supposition. Similarly, since cancer is often a systemic disease, local control will become a more pressing issue as systemic micrometastatic disease is eradicated with effective chemotherapy. Unfortunately, randomized trials testing the effectiveness of modern postoperative radiation therapy in the chemotherapy era have not been performed. Clinicians must therefore counsel patients regarding the risk of disease recurrence after surgery, the potential but unproven benefit of postoperative radiation therapy, and the possibility of treatment-related complications.     

Where do we stand with hepatoblastoma? A review

Hepatoblastoma (HB) is the most common pediatric liver malignancy, comprising approximately 1% of all pediatric cancers. The disparate clinical staging systems and histologic classifications that were developed during the last decades, nevertheless, reflect the remaining difficulties and uncertainties in characterizing HB. Furthermore, the combination of surgery and (neo)adjuvant chemotherapy has improved patient outcomes dramatically. A poor prognosis is associated with large tumor size, multifocality, extrahepatic disease, and metastatic spread. The exact etiology of HB remains unknown, but the cytogenetic alterations, phenotypic features, and biologic aspects that accompany this neoplasm yield more and more insight into its pathogenesis. New cell-biologic and molecular-biologic insights may lead to the development of new treatment modalities, especially for patients with a bad prognosis. This review summarizes the different aspects of this intriguing tumor and discusses the current status of research and treatment for patients with HB.     

Prevention of ER-negative breast cancer: where do we stand?

Oestrogen receptor-negative and triple-negative breast cancers are types of aggressive tumours that account for approximately 30 and 15% of total breast cancers, respectively. Selective oestrogen receptor modulators and aromatase inhibitors are unable to treat and prevent these subtypes of mammary tumours. Thus, it is worth identifying new pathways, biomarkers, and agents that are effective in the treatment and prevention of these subtypes. Several classes of drugs have been studied, and many are still currently under investigation. We have attempted to conduct a state-of-the-art study on this important issue.     

Recent translational research: antiangiogenic therapy for breast cancer – where do we stand?

The central importance of angiogenesis and our understanding of how new blood vessels are formed have led to the development of novel antiangiogenic therapies. Although the number of agents in development has grown exponentially, only one phase III trial in breast cancer has been completed. In that study the addition of bevacizumab to capecitabine did not extend the progression-free survival of patients with refractory disease as compared with capecitabine monotherapy. Early enthusiasm for antiangiogenic therapy must give way to clinical reality. Our challenge now is to exploit better the activity of antiangiogenic agents seen in the early clinical studies.     

Do we need to routinely perform cavity shaving with breast-conserving surgery for breast cancer? A systematic review and meta-analysis

AimsTo evaluate comparative outcomes of breast-conserving surgery (BCS) of breast cancer with and without cavity shaving.MethodsA systematic search of multiple electronic data sources was conducted, and all randomised controlled trials (RCTs) comparing BCS with or without cavity shaving for breast cancer were included. Positive margin rate, second operation rate, operative time, post-operative haematoma, cosmetic appearance and budget cost were the evaluated outcome parameters for the meta-analysis.ResultsSix RCTs reporting a total number of 971 patients; 495 of these underwent BCS plus shaving (BCS + S), and 473 underwent BCS alone were included. BCS + S showed significantly lower positive margin rate (Risk Ratio [RR] 0.40, P = 0.00001) and second operation rate (RR 0.38, P = 0.00001). BCS + S demonstrated longer operative time than BCS (79 ± 4 min vs 67 ± 3 min, Mean Difference 12.14, P = 0.002), and there was no significant difference in the risk of post-operative haematoma (RR 0.33, P = 0.20).ConclusionBCS + S is superior to BCS in terms of positive margins rate and second operation rate. Operative time is longer when cavity shaving is performed.     

Multinational clinical trials in oncology and post-trial benefits for host countries: where do we stand?

International collaboration has undoubtedly played a key role in the extraordinary progress we have witnessed in some areas of oncology in recent years. It has allowed us, for instance, to design trials large enough to depict very small benefits, as well as high-quality trials in less incident types of cancer. For different reasons, developing countries have also shown growing interest in this international effort and have been participating in many international trials. However, the ever-growing costs of novel anti-cancer treatments and technologies have created unprecedented difficulties for health economies in developing countries. Although the issue of individual benefit for patients must also be taken into account, the actual benefit for their society may be minimal. This paper discusses the ethics of including patients from non-developed countries in clinical trials evaluating the role of treatments that are unlikely to be made available to them after the trial because of prohibitive costs. Upfront arrangements ensuring post-trial access to interventions that have been proven successful might be the best alternative to exclusion from the research.     

Intrauterine exposures, pregnancy estrogens and breast cancer risk: where do we currently stand?

Since 1990, when a hypothesis on intrauterine influences on breast cancer risk was published, several studies have provided supportive, indirect evidence by documenting associations of birth weight and other correlates of the prenatal environment with breast cancer risk in offspring. Recent results from a unique cohort of women with documented exposure to diethylstilbestrol in utero have provided direct evidence in support of a potential role of pregnancy oestrogens on breast cancer risk in offspring.     

Mediastinal (thymic) large B-cell lymphoma: where do we stand?

Mediastinal (thymic) B-cell lymphoma (MBL) is a locally highly aggressive tumour that was first definitively described in the early 1980s. The incidence of MBL is low, which made disease characterisation difficult initially. However, MBL has several peculiar clinical, morphological, immunological, and genetic features. Collectively, these characteristics distinguish it from other diffuse, large B-cell lymphomas. Consequently, MBL has become a defined subtype of diffuse large B-cell lymphoma with its own code (9679/3) in the International Classification of Diseases. New insights into the biological and clinical aspects of MBL have been gained from the study of large numbers of cases. Nevertheless, the histogenesis of the disease is not yet fully understood. We review the available data on MBL with special emphasis on its morphological, immunological, and genetic properties. Also discussed are recent data on molecular genetics, biology, and treatment.     

Laparoscopic surgery for gastric cancer: where are we now and where are we going?

Introduction: Minimally-invasive surgery is gaining increasing popularity for the management of gastric cancer (GC).

Areas covered: The authors hereby comprehensively and systematically reviewed the randomized and/or prospective evidence on laparoscopic gastrectomy (LG) for GC. For early GC located in the distal stomach, various randomized trials have demonstrated the superiority/non-inferiority of LG especially in reducing surgical trauma and enhancing postoperative recovery without compromising surgical safety and oncologic efficacy. For advanced GC, while multicenter large-scale randomized evidence has demonstrated the safety and feasibility of LG by experienced hands, the long-term survival which is to be clarified by several ongoing trials are crucial to determine whether a more widespread application is acceptable. Randomized evidence regarding the application of laparoscopic total or proximal gastrectomy, which is technically challenging, is scarce. Various attempts in modification of the traditional laparoscopic approach to further reduce the trauma have been evaluated, such as single-incision and totally LG. LG is becoming increasingly individualized and precise.

Expert commentary: The current randomized and/or prospective evidence supports the non-inferiority of laparoscopic surgery especially for the management of early GC located in the distal stomach, while the definitive efficacy of the laparoscopic approach for more surgically challenging situations remains largely explorative and investigative.