Advantage Of Neoadjuvant Therapy Research Articles

Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer.

Simple SummaryNeoadjuvant therapy is recommended as standard care for patients with locally advanced resectable esophageal cancer. Neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) have convincingly been shown to improve the survival rate compared with surgery alone based on the results of several randomized clinical trials. Immunotherapy has become a new research direction in the field of EC research due to its great curative effects. However, controversies still remain in regard to identifying the most appropriate combination of nCT, nCRT, immunotherapy, and surgery, optimizing more effective neoadjuvant treatment protocols and surveillance strategies. This review comprehensively summarizes the research progress and describes and discusses the outcomes, pros, and cons of current trials. We believe our work has great academic value and will be of great help for researchers to understand the domestic and foreign research status in the field of neoadjuvant therapy in EC.Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased risk of local–regional recurrence and distant metastasis. Thus, it has been recommended as standard treatment for patients with resectable EC. However, several fundamental problems remain. First, the combination of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), and surgery for EC patients with different histological types remain controversial. Furthermore, to reduce the toxicity of preoperative chemotherapy and the risk of complications caused by preoperative radiation therapy, the treatment protocols of nCT and nCRT still need to be investigated and optimized by prospective trials. Moreover, for patients with complete clinical response following neoadjuvant therapy, it is worth ascertaining whether a “watch and wait” surveillance plus surgery-as-needed policy is more favorable, as well as, in addition to preoperative chemoradiotherapy, whether immunotherapy, especially when combined with the traditional neoadjuvant therapy regimens, brings new prospects for EC treatment. In this review, we summarize the recent insights into the research progress and existing problems of neoadjuvant therapy for locally advanced resectable EC.

Clinical experience in using sorafenib in patients with advanced kidney cancer

In the era of targeted therapy, the attention of researchers is focused on the role of neoadjuvant targeted therapy in the treatment of patients with renal cell carcinoma. The advantages of neoadjuvant therapy for advanced renal cell carcinoma include: detection of patients with primary refractory tumors, recurring tumors, simple onset of systemic therapy. One of the most popular and suitable for neoadjuvant targeted therapy is sorafenib. The use of this drug, in our opinion, can significantly improve the results of treatment of such patients. The article describes the description of 3 clinical observations of a widespread cancer of the kidneys treated in a somatic mode in the neoadjuvant mode. Range of therapeutic effects from progressive diseases to stabilization.

PTU-140 Neoadjuvant therapy toxicity and efficacy in oesophago-gastric cancer

Introduction The advantages of neoadjuvant therapy (NAT) in oesophago-gastric (OG) cancer have been proven in randomised trials. Benefits are modest and likely to be restricted to patients who respond well to therapy. The risks may outweigh benefits in earlier stages of disease. This study explores the risks associated with NAT, analyses which patients benefit and investigates whether there is a need for a change in NAT treatment strategy. Method All patients planned for surgical resection of OG cancer in this unit between 01/2010 and 12/2014 were identified. Part a) patients were divided according to pre-operative stage. Within each stage, survival was compared in patients undergoing NAT and those undergoing surgery alone. Similar comparisons were made with the NAT group further divided into histological responders and non-responders. Part b) from the cohort, patients undergoing NAT were identified. Adverse effects (AE) were recorded and graded according to the Common Terminology Criteria for Adverse Events v3.0. The relationships between the presence of AE and a range of variables were investigated along with survival. Survival analyses were undertaken by plotting Kaplan-Meier curves. Groups were compared using the Log Rank (Mantel-Cox) test. Results 587 patients were identified from the database. Part a) only stage III patients had improved survival with NAT vs. surgery alone (P = 0.02). Those in stage II with a histological response to treatment showed a trend towards better survival vs. surgery alone (P = 0.058). In all patients above the threshold for offering NAT (≥stage II), survival was no different in non-responders vs. those having surgery alone. Age and performance status were lower in the NAT group vs. the surgery only group and were both associated inversely with survival. This could mean NAT effects are overestimated and true survival in non-responders to NAT may be poorer than in patients having surgery alone. Part b) 376 patients received NAT and 88 (23.4%) suffered AE. 69% of these were severe, life-threatening or fatal. NAT course completion rate was lower in patients suffering AE vs. those not (P = 0.003). 20.5% patients with AE did not proceed to resection vs. 6.4% without AE (P = 0.001). Survival was better in patients without AE vs. with AE (P = 0.02) and was better in those undergoing resection (P Conclusion Efficacy of NAT is dependent on cancer stage and histological response to NAT. AE are common, often severe and associated with a reduced resection rate and survival. Identifying a means of predicting response to NAT is of great importance and should be used to guide treatment alongside/instead of disease stage. Disclosure of interest None Declared.

What more do we want from neoadjuvant treatment strategies in rectal cancer?

Radiation therapy (RT) delivered preoperatively has clearly shown to improve local disease control after radical surgery in rectal cancer [1–3]. In fact different options including short-course or long-course regimens have been extensively studied with similar good long-term local disease control [4–6]. Also, the addition of chemotherapy with fluoropyrimidine to radiation led to further improvement in local disease control of these patients [7,8]. At a first glance, the issue of local recurrence in rectal cancer had been solved with widespread introduction of preoperative RT with or without concomitant chemotherapy. So why do we keep searching for alternative treatment options for the already successful neoadjuvant approach? What are we looking for? First of all, the observation that neoadjuvant chemoradiation (CRT) could result in complete tumor eradication, also known as complete pathological response is now considered one of the major advantages of neoadjuvant therapy in patients with rectal cancer [9]. Patients with complete pathological response (pCR) are associated with improved oncological outcomes [10]. Therefore, development of alternative neoadjuvant strategies that could maximize pCR rates is highly desirable. Also, even though increased rates of sphincter preservation have been considered another advantage of the neoadjuvant strategy, none of the randomized studies have demonstrated any superiority in sphincter preservation rates in experimental arms of these studies [11]. However, in select patients with clinical and radiological evidence of pCR (complete clinical response [cCR]), alternative organ-preserving treatment strategies have been suggested [12,13]. Therefore, a substantial increase in pCR and cCR rates could benefit patients by improving oncological outcomes and truly affecting sphincter or even organ preservation rates [9]. Therefore, maximization of pCR/cCR rates is an excellent reason for the search of improved neoadjuvant treatment regimens. But radiation therapy comes at a significant cost for patients, even though some

Neoadjuvant chemotherapy for soft tissue sarcoma

Soft tissue sarcoma is a rare and very heterogeneous disease. The prognosis of these cancers is mainly influenced by histological grading size location and type of histology. Many aspects argue in favor of neoadjuvant chemotherapy but no singular trial could unambiguously prove an advantage of neoadjuvant therapy. This short review has a focus on neoadjuvant chemotherapy as induction therapy prior to chemoradiation or neoadjuvant chemotherapy alone.

Extending Neoadjuvant Care through Multi-Disciplinary Collaboration: Proceedings from the Fourth Annual Meeting of the Canadian Consortium for Locally Advanced Breast Cancer

The use of systemic therapy before surgery (“neoadjuvant therapy”) is the standard of care for the treatment of locally advanced and nonoperable breast cancer. The advantages of neoadjuvant therapy include improved rates of breast-conserving surgery, the possibility of early measurement of response, and potentially improved outcomes for certain subgroups of high-risk patients. The use of neoadjuvant therapy in operable breast cancer is increasing, although there are no clear guidelines in Canada to help guide patient selection and management. Multidisciplinary experts in the diagnosis and treatment of locally advanced breast cancer (labc) converged at the fourth annual meeting of the Canadian Consortium for LABC (colab) to further their goals of improved standards for neoadjuvant care and clinical research through education and collaboration. Canadian clinical researchers were joined by Dr. Michael Untch of the Helios Hospital Berlin–Buch—representing the German neoadjuvant treatment groups German Gynecologic Oncology Working Group (Arbeitsgemeinschaft Gynakologische Onkologie) and German Breast Group—to discuss the advancement of research in the neoadjuvant setting and important issues of clinical care and investigator-led research. The group reached a consensus on the importance of multidisciplinary collaboration, the use of clips to mark tumour location, and core biopsy testing for the estrogen and progesterone receptors and the human epidermal growth factor receptor 2 at the time of diagnosis. Other initiatives—including creation of a prospective database, inception of the colab Neoadjuvant Network, and development of a clinical survey to evaluate current practice—continue to further the colab mandate of transforming the neoadjuvant treatment landscape in Canada.

Using neoadjuvant therapy for breast cancer in clinical practice: when and how?

The roles of neoadjuvant therapy both as a standard thera-peutic approach and a research tool are very closely tied andhave yielded insights into both breast cancer biology andnew drug development [1, 2]. From a clinician’s standpoint,however, the key questions that arise revolve around theclinical advantages of neo-adjuvant therapy in terms ofsurgical outcomes, long-term recurrence/mortality anddecision-making. At the current time, the main advantage ofneoadjuvant therapy is to improve the odds of adequatesurgical resection, particularly breast-conserving surgery[3, 4]. Beyond that, long-term outcomes or clinical deci-sion-making do not appear to be affected by the sequence ofsystemic therapy in relation to definitive surgery. It isbecoming clear that breast cancer is heterogeneous. Ge-nomically defined subsets, which map to some extent withhormone and HER2 receptor subtypes, exhibit differentialrecurrence hazard reductions with systemic therapies—andthis concept also applies to neoadjuvant therapy response aswell [5]. But there is also clinical diversity, for example,contrasting rapid onset inflammatory cancer to a moreindolent cancer that has been clinically present for severalyears. Therefore, current neoadjuvant treatment paradigmsmust incorporate the base of evidence from large scaleclinical trials as well as the biological context of the disease.The reports contained in this special issue of Breast CancerResearch and Treatment highlight current trends and resultsthat are shaping both patient care and research in this area.The report by Lin et al.[6] demonstrate biological dif-ferences between interval and screen-detected cancerstreated on a prospective trial, even though the number ofscreening-detected cancers was small, as would be typicalin a neoadjuvant trial where the majority of patients werenot undergoing screening. As expected, interval cancershad a tendency to be hormone receptor-negative and ofhigher grade, whereas screen-detected cancers were all ofthe luminal intrinsic subtypes by gene expression array.Nevertheless, this report points to the need to stratifypatients by known characteristics associated with responsein clinical trials and to use established factors in routineclinical practice. For example, it is now clear that patientswith hormone receptor-positive cancer have less responseto neoadjuvant therapy and lower pathologic completeresponse (pCR) rates. Receptor status might thereforeaffect the decision regarding the timing of chemotherapy,especially if breast-conserving surgery is driving thedecision. Several phenotypes that are also related to hor-mone receptor content, but appear to have independentprognostic factors for response, such as proliferation indexand risk score by gene profile assays are the next markerson the horizon that could enter into this decision-making iftumor size reduction is a main goal of therapy [7, 8].Is there an optimum neoadjuvant regimen? Should non-standard adjuvant regimens that yield high pCR rates beadopted into routine practice? Until neoadjuvant trials arepowered for long-term outcome, at the current time, it isimportant to remember that the most important benefit ofneoadjuvant therapy is its ‘‘adjuvant’’ effect on long-termrecurrence and mortality. Therefore, an evidence-basedapproach would dictate the use of proven standard adjuvantregimens in the neoadjuvant setting. However, trials thatbridge pCR rates in relevant subsets to long-term outcomecould serve as the basis for approvals of new drugs andregimens and eventually shorten regulatory approval times[9]. Some long-standing standards may need to be

Neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients

Background Neoadjuvant chemotherapy is administered to control disease, make surgical resection possible and increase the possibility of breast tissue conservation. A further advantage of neoadjuvant therapy is that it helps to assess chemo-sensitivity to a particular agent. Induction of a pathological complete response (pCR) is one of the primary goals of neoadjuvant therapy in order to achieve a better disease-free and overall survival. Experimental data suggest that BRCA1 related breast cancer may have increased sensitivity to platinum-based chemotherapy, but clinical data are limited. The aim of this study was to evaluate the frequency of complete pathologic response after neo-adjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation.

Neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients

502 Background: Neoadjuvant chemotherapy is administered to control disease, make surgical resection possible and increase the possibility of breast tissue conservation. A further advantage of neoadjuvant therapy is that it helps to assess chemo-sensitivity to a particular agent. Induction of a pathological complete response (pCR) is one of the primary goals of neoadjuvant therapy in order to achieve a better disease-free and overall survival. Experimental data suggest that BRCA1 related breast cancer may have increased sensitivity to platinum-based chemotherapy, but clinical data are limited. The aim of this study was to evaluate the frequency of complete pathologic response after neo-adjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation. Methods: Twenty five women with breast cancer and a BRCA1 mutation with stage I, II, and III breast cancer between December 2006 and December 2008 were entered into this study. Patients were treated with cisplatin 75 mg/m2 intravenously every three weeks for four cycles. After chemotherapy, patients underwent surgery and were assessed for pathologic response in both the breast and axillary lymph nodes. Complete pathologic response was defined as no residual invasive disease in both the breast and axilla, however ductal carcinoma in situ was allowed. Results: Twenty five patients were enrolled in the study. Thirteen patients had tumors of greater than two centimeters (52%) and seven patients had positive lymph nodes at diagnosis (28%). Twenty two patients completed four cycles of cisplatin (88%) and three patients completed two cycles (12%). Clinical complete response was observed in eighteen patients (72%). Pathologic complete response was observed in eighteen patients (72%). Conclusions: Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancers. Clinical trials are warranted to determine the optimum treatment for this subgroup of breast cancer patients. No significant financial relationships to disclose.

Accessing the Aortopulmonary Window (#5) and the Paraaortic (#6) Lymph Nodes in Patients With Non-Small Cell Lung Cancer

The purpose of this study was to assess the efficacy of the different techniques of lymph node biopsies in patients with suspected metastatic non-small cell lung cancer (NSCLC) in the subaortic (station #5) and paraaortic (station #6) lymph nodes. This was a retrospective cohort study conducted of a prospective database of patients between January 2003 and June 2006 with suspected N2 disease only in the #5 or #6 lymph nodes, or both. All patients had integrated 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography, and nodal biopsy or thoracotomy, or both, with complete thoracic lymphadenectomy. There were 112 patients with clinically suspected N2 disease in lymph node stations #5 or #6, or both. The primary tumor was in the left upper lobe in 98 (88%) and in the left lower lobe in 14 (13%), and 58 had pathologic N2 disease in #5 or #6 lymph node stations only. Mediastinoscopy, used in all patients found, unsuspected N3 disease in 4 patients (3.6%) and N2 (#4L) disease in 12 (11%). Endoscopic ultrasound with fine needle aspiration (EUS-FNA), implemented in 62 patients (56%), correctly identified 41 patients (66%). Left single-incision video-assisted thoracic surgery (VATS) was used in 39 patients and was correct in 100%. Of the 58 patients, 53 (91%) completed neoadjuvant chemoradiotherapy, followed by resection, and their 5-year survival was 64%. EUS-FNA is less accurate for the #5 and #6 lymph node stations than left VATS. We prefer left VATS over the Chamberlain procedure for patients with suspected nodal metastases isolated only to #5 or #6 stations, and if positive, we prefer neoadjuvant therapy. The advantage of neoadjuvant therapy followed by resection compared with resection followed by adjuvant therapy remains controversial; and hence, the role for biopsy of these nodes is also controversial.

Integration of Systemic Chemotherapy in the Management of Primary Breast Cancer

Breast cancer cells can metastasize early in the development of primary tumors. Adjuvant chemotherapy improves disease-free survival and overall survival (OS) in patients with early-stage breast cancer, both in premenopausal and postmenopausal women. Tamoxifen improves OS in patients whose tumors are estrogen-receptor-positive, regardless of age. Although the relative risk reduction with these interventions is the same for all patients, the absolute benefit is more prominent in patients at the highest risk of relapse. All patients with involved lymph nodes should receive adjuvant chemotherapy if no contraindications occur. In patients with negative lymph nodes, adjuvant chemotherapy is recommended if the invasive tumor is moderately or poorly differentiated, the tumor size is larger than 1 or 2 cm, or hormone receptors are negative. Other prognostic and predictive indicators of response to chemotherapy and hormonal therapy remain investigational. Models that combine several factors to determine a patient's risk of relapse and death are presented. Neoadjuvant chemotherapy in conjunction with radiation therapy and surgery is the treatment of choice for patients with locally advanced breast cancer. Recently, this approach has been extended to patients with small, operable tumors. Neoadjuvant chemotherapy can downstage tumors effectively, leading to improved cosmetic results and possibly to a reduction in local recurrence rate. Another advantage of neoadjuvant therapy is the in vivo assessment of tumor sensitivity to chemotherapy, which allows optimization of available therapeutic agents. One disadvantage of neoadjuvant chemotherapy is that preoperative treatment causes an alteration of information regarding lymph node status prior to systemic treatment. Although the optimal chemotherapy regimen has not been established, doxorubicin-containing regimens are considered superior to non-doxorubicin-containing regimens. The role of high-dose chemotherapy is not well defined in the adjuvant setting and remains investigational. The taxanes paclitaxel and docetaxel are moving rapidly from the metastatic setting to the adjuvant setting. A better understanding of the biology of breast cancer is providing molecular tools to study novel treatment approaches. Oncogenes and tumor suppressor genes are emerging as important indicators of response to chemotherapy. These molecules, in turn, become targets for therapy. Novel agents under development are presented.