Leveraging the power of pooled data for cancer outcomes research

Background: Clinical trials continue to be the gold standard for determining the effcacy of novel cancer treatments, but they may also expose participants to the potential risks of unpredictable or severe toxicities. The development of validated tools that better inform patients of the beneifts and risks associated with clinical trial participation can facilitate the informed consent process. The design and validation of such instruments are strengthened when we leverage the power of pooled data analysis for cancer outcomes research. Main body: In a recent study published in the Journal of Clinical Oncology entitled“Determinants of early mortal?ity among 37,568 patients with colon cancer who participated in 25 clinical trials from the adjuvant colon cancer endpoints database,”using a large pooled analysis of over 30,000 study participants who were enrolled in clinical trials of adjuvant therapy for early?stage colon cancer, we developed and validated a nomogram depicting the predictors of early cancer mortality. This database of pooled individual?level data allowed for a comprehensive analysis of poor prognostic factors associated with early death;furthermore, it enabled the creation of a nomogram that was able to reliably capture and quantify the beneift?to?risk proifle for patients who are considering clinical trial participation. This tool can facilitate treatment decision?making discussions. Conclusion: As China and other Asian countries continue to conduct oncology clinical trials, efforts to collate patient?level information from these studies into a large data repository should be strongly considered since pooled data can increase future capacity for cancer outcomes research, which, in turn, can enhance patient?physician discus?sions and optimize clinical care.     

Current oncologic applications of radiofrequency ablation therapies

Radiofrequency ablation (RFA) uses high frequency alternating current to heat a volume of tissue around a needle electrode to induce focal coagulative necrosis with minimal injury to surrounding tissues. RFA can be performed via an open, laparoscopic, or image guided percutaneous approach and be performed under general or local anesthesia. Advances in delivery mechanisms, electrode designs, and higher power generators have increased the maximum volume that can be ablated, while maximizing oncological outcomes. In general, RFA is used to control local tumor growth, prevent recurrence, palliate symptoms, and improve survival in a subset of patients that are not candidates for surgical resection. It’s equivalence to surgical resection has yet to be proven in large randomized control trials. Currently, the use of RFA has been well described as a primary or adjuvant treatment modality of limited but unresectable hepatocellular carcinoma, liver metastasis, especially colorectal cancer metastases, primary lung tumors, renal cell carcinoma, boney metastasis and osteoid osteomas. The role of RFA in the primary treatment of early stage breast cancer is still evolving. This review will discuss the general features of RFA and outline its role in commonly encountered solid tumors.     

Meta-analysis of trials comparing gemcitabine and pegylated liposomal doxorubicin for treatment in women with progressive or recurrent ovarian cancer

OBJECTIVE To evaluate the efficacy and adverse effects of gemcitabine versus pegylated liposomal doxorubicin in patients with progressive or recurrent ovarian cancer. METHODS We conducted a systematic literature search to identify all randomized controlled trials comparing gemcitabine and pegylated liposomal doxorubicin for progressive or recurrent ovarian cancer. Trial data were reviewed and extracted independently by 2 reviewers. We evaluated the quality of the included studies using the Handbook 5.0 recommend standards and then analyzed data by Cochrane Collaborations RevMan 5.0. RESULTS Two trials which included a total of 348 patients were analyzed. The results of meta-analysis showed that gemcitabine improved disease control rates significantly better than pegylated liposomal doxorubicin. A greater number of patients receiving gemcitabine experienced neutropenia compared with patients receiving pegylated liposomal doxorubicin; however, hand-foot syndrome and mucositis were more severe in patients receiving pegylated liposomal doxorubicin. CONCLUSION Gemcitabine provided a limited advantage compared with pegylated liposomal doxorubicin. There exists an urgent need for more high-quality, multicenter, adequate randomized, controlled clinical trials for comparing gemcitabine with pegylated liposomal doxorubicin in patients with progressive/recurrent ovarian cancer.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

Neoadjuvant chemotherapy in stage III NSCLC

Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related mortality in the United States. Current standard care for treating NSCLC is surgical resection, when feasible, followed by adjuvant chemotherapy in stages II and III. Neoadjuvant or induction chemotherapy may have several potential advantages compared with adjuvant chemotherapy and has been evaluated in randomized and nonrandomized clinical trials in NSCLC. This article reviews the data for neoadjuvant chemotherapy in NSCLC with a particular focus on regionally advanced disease (stage III) that is still amenable to surgical resection.     

Adjuvant chemotherapy for lung cancer: cisplatin doublets only?

Lung cancer is the leading cause of cancer-related mortality worldwide. Despite adequate resection, more than half of patients die of recurrent disease, usually at distant sites. Adjuvant systemic chemotherapy is mainly used to eradicate micrometastatic disease. Since the seminal 1995 meta-analysis from earlier studies showed a trend toward improved survival with the use of cisplatin-based adjuvant chemotherapy, several randomized prospective adjuvant trials have addressed this question and eventually established the role for platinum-based adjuvant chemotherapy in patients with stage II or IIIA non-small cell lung cancer who have undergone complete resection. The role of adjuvant chemotherapy in patients with stage I disease remains controversial. Although no clinical or molecular predictors of recurrent disease after surgical resection are reliable, encouraging preliminary data on gene expression studies suggest that identifying, and perhaps treating, only patients at high risk for relapse might be possible in the near future. Furthermore, molecular predictors of resistance may guide the selection of chemotherapy in this setting.     

Adjuvant therapy of non small-cell lung cancer

Multiple randomized prospective trials have failed to show a definitive survival advantage for the administration of adjuvant therapy following complete resection of non small-cell lung cancer.     

Surgical adjuvant chemotherapy in non-small cell carcinoma of the lung

A review of the published clinical trials of surgical adjuvant chemotherapy in lung cancer indicated that in the majority of nonrandomized trials, conclusions favored the use of adjuvant chemotherapy. On the other hand, most randomized trials were unable to show any statistically significant difference in survival or disease-free interval between treated groups and controls. On the contrary, in several studies the survival was better in the control group. It was concluded that adjuvant chemotherapy has no place in the routine treatment of resectable lung cancer; however, further prospective controlled randomized trials are needed using new agents, new combinations, or new schedules.     

Postsurgical adjuvant therapy in stages I, II, and IIIA non-small cell lung cancer

The prognostic importance of accurate staging of non-small cell lung cancer was established in 1974 and reaffirmed and refined in 1986. The concept of adjuvant therapy after pulmonary resection for lung cancer is justified by the behavior of the disease. The best available data pertinent to adjuvant therapy of lung cancer have been collected by The Lung Cancer Study Group over the past 13 years. These data are based on a commitment to prospective and standardized surgical staging as a basis for large-scale prospective randomized control trials. A treatment effect of combination chemotherapy has been detected for stage II and IIIA nonsquamous cancer and is suggested for squamous cancer as well. This treatment effect is of marginal clinical significance. Adjuvant therapy for stage I disease has not shown a detectable benefit. Adjuvant radiation therapy for stage II and IIIA squamous cell carcinoma likewise has not resulted in survival benefit. Systemic metastasis continues to be the major clinical problem in lung cancer treatment, and better systemic therapy is necessary to improve the outcome in this disease. However, some patients do benefit from adjuvant chemotherapy, and efforts to identify such patients prospectively are also the subject of current clinical research.     

Novel adjuvant therapies for pancreatic adenocarcinoma

Contemporary adjuvant therapy for pancreatic cancer patients following surgical resection includes chemotherapy and chemoradiotherapy. However, the median survival remains approximately 20 months despite multi-modality treatment using gemcitabine or fluoropyrimidine systemic chemotherapy. Adjuvant randomized trials are currently underway to evaluate cytotoxic combinations found to be active in advanced disease including FOLFIRINOX, gemcitabine/nab-paclitaxel and gemcitabine/capecitabine. Immunotherapy using genetically engineered cell-based vaccines had shown promise in resected pancreatic cancer patients during early phase trials, and algenpantucel-L vaccine is currently being evaluated in adjuvant setting in a randomized trial. This review focuses on novel adjuvant therapies currently in clinical evaluation.     

Adjuvant treatment of non-small-cell lung cancer: how do we improve the cure rates further?

Surgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.     

Surgical treatment of pancreatic cancer: the role of adjuvant and multimodal therapies.

Surgical treatment in specialized referral centers has improved the prognosis of resectable pancreatic cancer considerably despite the generally aggressive behavior of this malignancy. At the same time, adjuvant therapy for pancreatic cancer has been shown to be effective in providing a survival benefit. However, some controversy remains over whether to use chemotherapy alone or combined chemoradiation. Few prospective randomized controlled clinical trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation have demonstrated a distinct survival advantage of systemic chemotherapy (5-FU/FA or gemcitabine) following surgical resection. The most notable published trial is the European Study Group for Pancreatic Cancer (ESPAC)-1 trial. In addition, there are several retrospective analyses and two randomized studies on adjuvant radiation and chemoradiation. Some of these suggested increased survival rates using chemoradiation, which was subsequently widely introduced in clinical routine, especially in the United States. RCTs and a recent meta-analysis of these RCTs confirm, however, the superiority of chemotherapy over chemoradiation, except for a subgroup of patients with positive resection margins. Thus, curative surgery followed by adjuvant systemic chemotherapy should be the standard treatment for patients with resectable, locally confined pancreatic cancer. Further RCTs may clarify potential benefits of chemoradiation in the adjuvant treatment setting. Moreover, the best chemotherapy, or a combination thereof, remains to be determined in large-scale randomized trials.     

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.     

Adjuvant therapy for resected non-small-cell lung cancer: Recent advances,emerging agents,and lingering questions

Survival rates for all stages of non-small-cell lung cancer (NSCLC) are dismal. Despite complete resection of earlystage NSCLC, many patients have recurrence at distant metastatic sites, reinforcing the need for effective systemic adjuvant therapy. Chemotherapy, and more recently, targeted therapies, have been evaluated in the adjuvant setting. Although initial trials did not suggest improved survival, a 1995 meta-analysis favored adjuvant cisplatin-based chemotherapy. The recently published International Adjuvant Lung Trial confirms this finding and suggests a new standard of care. In this paper we review data on adjuvant chemotherapy and limitations of recent clinical trials, including those with targeted therapies. We also address the most effective and least toxic regimens for adjuvant chemotherapy and the subsets of patients likely to derive the most benefit.