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Neoadjuvant Therapy (neoadjuvant + therapy)
Selected AbstractsUSEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORSDIGESTIVE ENDOSCOPY, Issue 1 2005Masaho Ota Objective:, The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods:, Sixty-two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD-SD (progressive disease-stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as , 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results:, The percent reduction of the thickness of Grade 0,1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0,1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD-SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non-responders and 94% of responders. Conclusions:, The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma. [source] International survey on esophageal cancer: part II staging and neoadjuvant therapyDISEASES OF THE ESOPHAGUS, Issue 3 2009J. Boone SUMMARY The outcome of esophagectomy could be improved by optimal diagnostic strategies leading to adequate preoperative patient selection. Neoadjuvant therapy could improve outcome by increasing the number of radical resections and by controlling metastatic disease. The purposes of this study were to gain insight into the current worldwide practice of staging modalities and neoadjuvant therapy in esophageal cancer, and to detect intercontinental differences. Surgeons with particular interest in esophageal surgery, including members of the International Society for Diseases of the Esophagus, the European Society of Esophagology , Group d'Etude Européen des Maladies de l'Oesophage, and the OESO, were invited to participate in an online questionnaire. Questions were asked regarding staging modalities, neoadjuvant therapy, and response evaluation applied in esophageal cancer patients. Of 567 invited surgeons, 269 participated resulting in a response rate of 47%. The responders currently performing esophagectomies (n= 250; 44%) represented 41 countries across the six continents. Esophagogastroscopy with biopsy and computed tomography (CT) scanning were routinely performed by 98% of responders for diagnosing and staging esophageal cancer, while endoscopic ultrasound (EUS) and barium esophagography were routinely applied by 58% and 51%, respectively. Neoadjuvant therapy is routinely administered by 33% and occasionally by 63% of responders. Of the responders that administer identical neoadjuvant regimens to esophageal adenocarcinoma (AC) and squamous cell carcinoma, 54% favor chemoradiotherapy. For AC, chemotherapy is preferred by 31% of the responders that administer neoadjuvant therapy, whereas for squamous cell carcinoma, the majority of responders (38%) prefer chemoradiotherapy. Response to neoadjuvant therapy is predominantly assessed by CT scanning of the chest and abdomen (86%). Barium esophagography, EUS, and combined CT/PET scan are requested for response monitoring in equal frequency (25%). Substantial differences in applied staging modalities and neoadjuvant regimens were detected between surgeons from different continents. In conclusion, currently the most commonly applied diagnostic modalities for staging and restaging esophageal cancer are CT scanning of the chest and abdomen, gastroscopy, barium esophagography and EUS. Neoadjuvant therapy is routinely applied by one third of the responders. Intercontinental differences have been detected in the diagnostic modalities applied in esophageal cancer staging and in the administration of neoadjuvant therapy. The results of this survey provide baseline data for future research and for the development of international guidelines. [source] Neoadjuvant therapy as a paradigm to develop systemic cancer therapyDRUG DEVELOPMENT RESEARCH, Issue 7 2008Guru SonpavdeArticle first published online: 23 DEC 200 Abstract Neoadjuvant systemic therapy preceding definitive surgical resection permits the in vivo assessment of tumor response and induces pathologic downstaging in several malignancies. Since pathologic complete response (pCR) and biologic activity can be determined rapidly, the signal of efficacy of a systemic regimen is evident with a relatively small number of patients before long-term follow-up. Additionally, emerging data suggest that modulation of pharmacodynamic biomarkers after brief neoadjuvant therapy may correlate with long-term clinical outcomes. Early evidence for in vivo resistance and elucidation of mechanisms of resistance may assist with selection of rational combinations of agents as subsequent therapy to improve outcomes. Evidence of biologic anti-tumor activity in target-enriched subsets can be determined with a small number of patients in proof of principal pilot trials. Biologic activity against molecular targets and downstream anti-proliferative and pro-apoptotic activity may help with the selection of the lowest effective dose, which may lead to efficacious and safe therapy. Therefore, this paradigm has the potential to enable the efficient use of resources and accelerate the pace of systemic therapy development. It may also be possible to determine molecular and biologic characteristics that predict for sensitivity. Drug Dev Res 69:388,397, 2008. © 2008 Wiley-Liss, Inc. [source] Neoadjuvant therapy for locally advanced cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010Stephen F. Sener MD No abstract is available for this article. [source] Neoadjuvant therapy for breast cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010Stephen V. Liu MD Abstract The past few decades have seen an increase in both the role and the complexity of neoadjuvant therapy for breast cancer. Neoadjuvant therapy was initially described as systemic chemotherapy for inflammatory or locally advanced breast cancer but now entails a combination of chemotherapy, endocrine therapy, and targeted therapy. Neoadjuvant systemic therapy is employed for inoperable inflammatory and locally advanced breast cancer, and also for patients with operable breast cancers who desire breast-conserving therapy (BCT) but are not candidates based on the initial size of the tumor in relation to the size of the breast. Neoadjuvant therapy in this subset of patients may impact the surgical options. This review will summarize the benefits of neoadjuvant systemic therapy and implications for BCT, the timing of sentinel node biopsy, and the utility of magnetic resonance imaging (MRI) to predict response to therapy. J. Surg. Oncol. 2010; 101:283,291. © 2010 Wiley-Liss, Inc. [source] Neoadjuvant therapy of locally advanced gastric cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010James J. Mezhir MD Abstract Treatment of gastric cancer has evolved with the advent of randomized trials demonstrating chemotherapeutic agents with efficacy in advanced disease. Level I evidence supports delivering chemotherapy in the neoadjuvant setting; the data shows improvement in progression-free and overall survival. A clinical response to therapy is associated with improved R0 resection rates, pathologic response, and outcome in patients with locally advanced disease. Early assessment of metabolic response to therapy can potentially be utilized to tailor treatment. J. Surg. Oncol. 2010; 101:305,314. © 2010 Wiley-Liss, Inc. [source] Neoadjuvant therapy for pancreatic cancer: A current reviewJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010Daniel E. Abbott MD Abstract The optimal therapy for pancreatic cancer continues to evolve. Neoadjuvant chemoradiation is a key component of current treatment regimens, and evaluation of previous treatment options will help guide future trials. Here the authors present a review of the current literature with discussion of future directions. J. Surg. Oncol. 2010; 101:315,320. © 2010 Wiley-Liss, Inc. [source] Oesophagectomy for tumours and dysplasia of the oesophagus and gastro-oesophageal junctionANZ JOURNAL OF SURGERY, Issue 4 2009Krishna Epari Abstract Background:, Neoadjuvant therapy, radical lymphadenectomy and treatment in high-volume centres have been proposed to improve outcomes for resectable oesophageal tumours. The aim of the present study was to review the oesophagectomy experience of a single surgeon with a moderate caseload who uses neoadjuvant therapy selectively and performs a conservative lymphadenectomy. Methods:, A retrospective review of prospectively collected data was performed. The study included 125 consecutive attempted oesophageal resections performed by a single surgeon (RC) from 1993 to 2006. Results:, All patients were staged with computed tomography and also laparoscopy for lower third and junctional tumours. Endoscopic ultrasound was used in 69%. Seventy-seven per cent were adenocarcinomas. Neoadjuvant therapy was used selectively in 23%. One hundred and twenty-one resections were carried out, giving an overall resection rate of 97% with an R0 resection in 82%. In-hospital mortality was 0.8%, clinical anastomotic leak 1.7% and median length of stay 14 days. Overall median and 5-year survival were 46 months and 47%. Stage-specific 5-year survival was 100%, 71%, 41% and 21% for stages 0, I, II and III, respectively. Isolated local recurrence occurred in 8%. Conclusions:, A moderate volume surgeon with specialist training in oesophageal resectional surgery can achieve a low mortality and anastomotic leak rate with good survival outcomes. The role for neoadjuvant therapy and radical lymphadenectomy is controversial and remains to be clearly defined. Accurate preoperative staging is essential for selection of patients for curative surgery with or without neoadjuvant therapy and for comparison of results. [source] Risk factors for malnutrition after oesophageal and cardia cancer surgeryBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2008L. Martin Background: Oesophageal cancer surgery is often followed by malnutrition, but the factors causing weight loss are unknown. The aim of this population-based study was to identify such risk factors. Methods: Data were collected from a nationwide Swedish organization for research on surgery for oesophageal cancer. A total of 340 patients (75·9 per cent of those eligible) responded to a study-specific questionnaire concerning height and weight, just before and 6 months after surgery. Factors influencing malnutrition, defined as loss of body mass index of at least 15 per cent 6 months after operation, were identified by logistic regression. Results: Neoadjuvant therapy (received by 10·6 per cent of all patients) and female sex were associated with at least a twofold increased risk of weight loss (odds ratio (OR) 2·41 (95 per cent confidence interval 1·01 to 5·77) and 2·14 (1·07 to 4·28) respectively), whereas preoperative weight loss was associated with a decreased risk (OR 0·13 (0·03 to 0·65)). Age, tumour stage and location, type of oesophageal substitute, suture technique and postoperative complications did not influence the risk. Conclusion: Neoadjuvant therapy and female sex appear to be associated with an increased risk of malnutrition after oesophageal cancer surgery. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Neoadjuvant therapy for pancreatic cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2007J. Kleeff No good evidence of benefit,trials needed [source] Prospective evaluation of quality of life in patients with localized oesophageal cancer treated by multimodality therapy or surgery aloneBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2006J. V. Reynolds Background: Health-related quality of life (HRQL) outcomes are important in assessing new approaches to the treatment of cancer. Neoadjuvant therapy is being used increasingly before surgery in patients with localized oesophageal cancer. This prospective non-randomized study evaluated HRQL in patients treated by preoperative chemotherapy and radiation therapy followed by surgery (multimodal therapy) or by surgery alone. Methods: Data from European Organization for Research and Treatment of Cancer quality of life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, after chemoradiotherapy where applicable, and at 3, 6 and 12 months after surgery. Results: The study included 202 consecutive patients with oesophageal cancer considered suitable for curative (R0) resection at the time of staging. Eighty-seven patients received chemotherapy combined with external-beam radiotherapy before surgery. At baseline, 75 (86 per cent) of 87 patients in the multimodal group completed questionnaires, compared with 72 (62·6 per cent) of 115 in the surgery-alone group. There were no significant differences in baseline global HRQL scores between groups. Preoperative chemoradiotherapy significantly reduced physical (P = 0·004) and role (P = 0·007) functioning before surgery, despite a significant (P = 0·043) improvement in the dysphagia score. Oesophageal resection had a negative impact on global, functional and symptom HRQL scores at 3 months in both groups. Most variables had recovered by 6 months in the two groups, but at 12 months physical and role functioning remained impaired in the surgery-alone group, and social functioning and financial worries in the multimodal group. Conclusion: Although the multimodal regimen had a negative impact on HRQL before surgery, postoperative quality of life in patients who had multimodal therapy was similar to that in those who had surgery alone. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] NON-GYNAECOLOGICAL CYTOLOGY: THE CLINICIAN'S VIEWCYTOPATHOLOGY, Issue 2006I. Penman There is increased recognition of the importance of accurate staging of malignancies of the GI tract and lung, greater use of neoadjuvant therapies and more protocol-driven management. This is particularly important where regional lymph node involvement significantly impacts on curability. Multidetector CT and PET scanning have resulted in greater detection of potential abnormalities which, if positive for malignancy, would change management. There is also a greater recognition that many enlarged nodes may be inflammatory and that size criteria alone are unreliable in determining involvement. In other situations, especially pancreatic masses, not all represent carcinoma as focal chronic pancreatitis, autoimmune pancreatitis etc can catch out the unwary. A preoperative tissue diagnosis is essential and even if unresectable, oncologists are increasingly reluctant to initiate chemotherapy or enroll patients into trials without this. The approach to obtaining tissue is often hampered by the small size or relative inaccessibility of lesions by percutaneous approaches. As such novel techniques such as endoscopic ultrasound (EUS) guided FNA have been developed. A 120cm needle is passed through the instrument and, under real-time visualisation, through the gastrointestinal wall to sample adjacent lymph nodes or masses. Multiple studies have demonstrated the safety and performance of this technique. In oesophageal cancer, confirmation of node positivity by has a major negative influence on curative resection rates and will often lead to a decision to use neoadjuvant chemotherapy or a non-operative approach. Sampling of lymph nodes at the true coeliac axis upstages the patient to M1a status (stage IV) disease and makes the patient incurable. In NSCLC, subcarinal lymph nodes are frequently present but may be inflammatory. If positive these represent N2 (stage IIIA) disease and in most centres again makes the patient inoperable. Access to these lymph nodes would otherwise require mediastinosocopy whereas this can be done simply, safely and quickly by EUS. Overall the sensitivity for EUS , FNA of mediastinal or upper abdominal lymph nodes is 83,90% with an accuracy of 80,90%. In pancreatic cancer performance is less good but pooled analysis of published studies indicates a sensitivity of 85% and accuracy of 88%. In a recent spin-off from EUS, endobronchial ultrasound (EBUS) instruments have been developed and the ability to sample anterior mediastinal nodes has been demonstrated. It is likely that this EBUS , FNA technique will become increasingly utilised and may replace mediastinoscopy. The development of techniques such as EUS and EBUS to allow FNA sampling of lesions has increased the role of non-gynaecological cytology significantly in recent years. Cytology therefore remains important for a broad range of specialties and there is ongoing need for careful and close co-operation between cytologists and clinicians in these specialties. References:, 1. Williams DB, Sahai AV, Aabakken L, Penman ID, van Velse A, Webb J et al. Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience. Gut. 1999; 44: 720,6. 2. Silvestri GA, Hoffman BJ, Bhutani MS et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61: 1441,6. 3. Rintoul RC, Skwarski KM, Murchison JT, Wallace WA, Walker WS, Penman ID. Endobronchial and endoscopic ultrasound real-time fine-needle aspiration staging of the mediastinum ). Eur Resp J 2005; 25: 1,6. [source] Histopathologic effects of neoadjuvant therapies for advanced squamous cell carcinoma of the esophagus: multivariate analysis of predictive factors and p53 overexpressionDISEASES OF THE ESOPHAGUS, Issue 1 2002Y. Kajiyama SUMMARY. In 97 patients (60, chemotherapy; 22, chemoradiotherapy; 15, radiotherapy), histopathologic effects were evaluated microscopically, and histologic response rates were compared among three neoadjuvant treatment modalities. Predictive factors for neoadjuvant therapies were analyzed by logistic regression, including the results of p53 immunohistochemical staining. In the chemoradiotherapy group, the pathologic response rate was 86.4%, and was significantly higher than that for chemotherapy (P < 0.0001) or for radiotherapy (P = 0.0031). In patients with normal p53 protein expression, the histopathologic response rate to chemotherapy was 20.0%, a higher rate than that for patients with abnormal p53 overexpression. In the chemoradiotherapy or radiotherapy group, however, the response rates were almost the same, irrespective of p53 oncoprotein status. From multivariate analysis, the neoadjuvant treatment modality itself was identified as the most powerful predictive factor for the effect. Chemoradiotherapy had the most powerful effect on advanced esophageal cancer, and p53 status did not influence the clinical outcome in this group. [source] USEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORSDIGESTIVE ENDOSCOPY, Issue 1 2005Masaho Ota Objective:, The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods:, Sixty-two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD-SD (progressive disease-stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as , 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results:, The percent reduction of the thickness of Grade 0,1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0,1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD-SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non-responders and 94% of responders. Conclusions:, The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma. [source] Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-upDISEASES OF THE ESOPHAGUS, Issue 2 2010M. Zemanova SUMMARY Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44,76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5-fluorouracil (5-FU), 200 mg/m2/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty-four patients (41%) were furthermore non-randomly assigned to paclitaxel 200 mg/m2/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4,8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy-eight patients (73%) had surgery and 63 of them were completely resected. Twenty-two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node-negative and esophageal wall-positive residual disease. There were 10 surgery-related deaths, mostly due to pulmonary insufficiency. Twenty-nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow-up of 52 months (range 27,80), median survival of 18.0 months and 1-, 2-, 3- and 5-year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non-hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long-term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non-hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect. [source] International survey on esophageal cancer: part II staging and neoadjuvant therapyDISEASES OF THE ESOPHAGUS, Issue 3 2009J. Boone SUMMARY The outcome of esophagectomy could be improved by optimal diagnostic strategies leading to adequate preoperative patient selection. Neoadjuvant therapy could improve outcome by increasing the number of radical resections and by controlling metastatic disease. The purposes of this study were to gain insight into the current worldwide practice of staging modalities and neoadjuvant therapy in esophageal cancer, and to detect intercontinental differences. Surgeons with particular interest in esophageal surgery, including members of the International Society for Diseases of the Esophagus, the European Society of Esophagology , Group d'Etude Européen des Maladies de l'Oesophage, and the OESO, were invited to participate in an online questionnaire. Questions were asked regarding staging modalities, neoadjuvant therapy, and response evaluation applied in esophageal cancer patients. Of 567 invited surgeons, 269 participated resulting in a response rate of 47%. The responders currently performing esophagectomies (n= 250; 44%) represented 41 countries across the six continents. Esophagogastroscopy with biopsy and computed tomography (CT) scanning were routinely performed by 98% of responders for diagnosing and staging esophageal cancer, while endoscopic ultrasound (EUS) and barium esophagography were routinely applied by 58% and 51%, respectively. Neoadjuvant therapy is routinely administered by 33% and occasionally by 63% of responders. Of the responders that administer identical neoadjuvant regimens to esophageal adenocarcinoma (AC) and squamous cell carcinoma, 54% favor chemoradiotherapy. For AC, chemotherapy is preferred by 31% of the responders that administer neoadjuvant therapy, whereas for squamous cell carcinoma, the majority of responders (38%) prefer chemoradiotherapy. Response to neoadjuvant therapy is predominantly assessed by CT scanning of the chest and abdomen (86%). Barium esophagography, EUS, and combined CT/PET scan are requested for response monitoring in equal frequency (25%). Substantial differences in applied staging modalities and neoadjuvant regimens were detected between surgeons from different continents. In conclusion, currently the most commonly applied diagnostic modalities for staging and restaging esophageal cancer are CT scanning of the chest and abdomen, gastroscopy, barium esophagography and EUS. Neoadjuvant therapy is routinely applied by one third of the responders. Intercontinental differences have been detected in the diagnostic modalities applied in esophageal cancer staging and in the administration of neoadjuvant therapy. The results of this survey provide baseline data for future research and for the development of international guidelines. [source] Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2008T. Kaur SUMMARY., The ability of reactive oxygen species to induce cellular damage and to cause cell death opens the possibility of exploiting this property in the treatment of esophageal cancer through a free radical mediated mechanism. The present study was carried out with the aim of evaluating the changes in the antioxidant defense status in esophageal cancer patients treated without and with neoadjuvant therapy (NAT). Forty surgically resected tissue specimens from tumors, tissue adjoining the tumors and paired macroscopically normal mucosa were obtained from esophageal cancer patients treated with or without chemo-radiotherapy. An evaluation of antioxidant defense system in the normal, adjoining and tumor esophageal tissues in response to NAT revealed decreased catalase activity in tumor and adjoining tissues as compared to their respective normal tissue levels. Similarly, decreased superoxide dismutase activity was observed in tumor tissue in response to NAT. In both the treatment groups (with and without NAT), no significant change was observed in the enzyme activity of glutathione reductase in the normal, adjoining and tumor tissues. Enhanced glutathione peroxidase activity was found in tumor tissue, as compared to the adjoining and paired normal tissue of patients after NAT. Estimation of reduced glutathione (GSH) levels showed a significant decline in GSH levels in esophageal tumors after NAT. Depletion of GSH, an endogenous antioxidant, would elevate drug sensitivity and might predispose neoplastic cells to apoptosis in response to NAT. The antioxidant enzymes in the esophageal carcinoma thus may play an important role in influencing the final outcome upon NAT course. [source] Neoadjuvant therapy as a paradigm to develop systemic cancer therapyDRUG DEVELOPMENT RESEARCH, Issue 7 2008Guru SonpavdeArticle first published online: 23 DEC 200 Abstract Neoadjuvant systemic therapy preceding definitive surgical resection permits the in vivo assessment of tumor response and induces pathologic downstaging in several malignancies. Since pathologic complete response (pCR) and biologic activity can be determined rapidly, the signal of efficacy of a systemic regimen is evident with a relatively small number of patients before long-term follow-up. Additionally, emerging data suggest that modulation of pharmacodynamic biomarkers after brief neoadjuvant therapy may correlate with long-term clinical outcomes. Early evidence for in vivo resistance and elucidation of mechanisms of resistance may assist with selection of rational combinations of agents as subsequent therapy to improve outcomes. Evidence of biologic anti-tumor activity in target-enriched subsets can be determined with a small number of patients in proof of principal pilot trials. Biologic activity against molecular targets and downstream anti-proliferative and pro-apoptotic activity may help with the selection of the lowest effective dose, which may lead to efficacious and safe therapy. Therefore, this paradigm has the potential to enable the efficient use of resources and accelerate the pace of systemic therapy development. It may also be possible to determine molecular and biologic characteristics that predict for sensitivity. Drug Dev Res 69:388,397, 2008. © 2008 Wiley-Liss, Inc. [source] Surgical margin determination in head and neck oncology: Current clinical practice.HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2005Neck Society Member Survey, The results of an International American Head Abstract Background. Our aim was to investigate the ways in which surgeons who perform head and neck ablative procedures on a regular basis define margins, how they use frozen sections to evaluate margins, and the effect of chemoradiation on determining tumor margins. Methods. A custom-designed questionnaire was mailed to members of the American Head and Neck Society asking members how they evaluate and define tumor margins. Results. Of 1500 surveys mailed, 476 completed surveys were received. The most common response for distance of a clear pathologic margin was >5 mm on microscopic evaluation. A margin containing carcinoma in situ was considered a positive margin by most, but most did not consider a margin containing dysplasia a positive margin. When initial frozen section margins are positive for tumor and further resection results in negative frozen section margins, 90% consider the patient's margin negative. Most surgeons sample the frozen section from the surgical bed rather than from the main specimen. Nearly half use wider margins when resecting tumors treated with neoadjuvant therapy. When resecting recurrent or residual tumors treated with previous chemoradiation therapy, most resect to the pretreatment margin. Conclusions. No uniform criteria to define a clear surgical margin exist among practicing head and neck surgeons. Most head and neck surgeons consider margins clear if resection completed after an initial positive frozen section margin reveals negative margins, but this view is not shared by all. Most surgeons take frozen sections from the surgical bed; however, error may occur when identifying the positive margin within the surgical bed. The definition of a clear tumor margin after chemoradiation is unclear. These questions could be addressed in a multicenter prospective trial. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] The case against preoperative biliary drainage with pancreatic resectionHPB, Issue 6 2006Rurik C. Johnson The majority of patients with periampullary malignancies currently undergo biliary drainage before pancreaticoduodenectomy. Placement of an endoprosthesis reliably ameliorates jaundice and pruritus. However, preoperative biliary drainage leads to bile colonization and increases the risk of postoperative wound infection after pancreatic resection. Preoperative biliary drainage does not appear to lower postoperative morbidity or mortality following pancreatic resection and does not lower but probably increases costs associated with pancreatic resection. Preoperative biliary drainage is frequently used with little clinical benefit and its utilization should be limited to specific clinical indications, i.e. patients receiving neoadjuvant therapy, patients waiting several weeks or more for surgical evaluation and resection, patients with cholangitis. [source] Histologic upgrading of prostate cancer occurs frequently over a short period of time: Single hospital experiences of radical prostatectomyINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2001Hideki Mukouyama Abstract A total of 163 patients with localized prostate cancer underwent retropubic radical prostatectomy and pelvic lymphadenectomy at a single hospital from 1989 to 1998. We reviewed the patients in terms of their prognostic factors and survival. The patients without advanced diseases were diagnosed as having prostate carcinoma, using either biopsies or transurethral resection of the prostate. The carcinomas were categorized into localized prostate carcinomas (stage A, B or C) as a result of digital rectal examinations, computed tomography scans and bone scans. The patients were informed of the risk of surgery and, if they agreed to sign the consent form, underwent radical prostatectomy under general and epidural anesthesia usually 2 months after a positive biopsy. The surgical specimens were sent for pathology and were graded according to classifications of well-, moderately and poorly differentiated adenocarcinoma. The patients were usually discharged from the hospital 2,3 weeks postoperatively and had regular follow-up treatment. The mean age (± SD) was 68.75 (± 5.59) years and the mean follow-up period was 47.2 months. There was a significant difference (34.4%) in pathologic grades between biopsy and surgical specimen. In a quarter of the patients (approximately 26.4%) upgrading of the surgical report occurred despite neoadjuvant therapy. Three-year, 5-year and 7-year actuarial survival rates were 91.8%, 79.9% and 71.9%, respectively. Patients with organ-confined prostate cancer underwent radical prostatectomy and survived a fairly good period of time. Histologic upgrading was frequently observed within a short period of time (2 months). [source] Prediction of organ-confined disease by prostate-specific antigen nadir after neoadjuvant therapyINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2000Takahiko Hachiya Abstract Background It is not clear whether or not serum prostate-specific antigen (PSA) levels after androgen deprivation prior to radical prostatectomy (neoadjuvant therapy) have any value in the prediction of the final pathologic stage. Methods We conducted a study on 49 patients who underwent retropubic radical prostatectomy following neoadjuvant therapy for clinical stage T1c, T2, and T3a prostate cancer. We evaluated progression-free survival based on the PSA failure rate and the predictive value of the PSA nadir after neoadjuvant therapy and other clinical factors to determine the most important predictor of organ confinement. Results Of the 49 patients, 30 had organ-confined disease. Of 31 patients without adjuvant therapy after surgery, the PSA failure-free rates at 2 years were 81.6 and 34.3% in the subset of organ-confined disease and non-organ-confined disease, respectively (P = 0.0031). Of the 18 patients with adjuvant androgen deprivation therapy after surgery, the PSA failure-free rate at 2 years was 100% and 59.7% in patients with organ-confined disease and non-organ-confined disease, respectively. Baseline PSA (P = 0.037), PSA nadir (P < 0.0001) and PSA density (P = 0.003) significantly correlated with organ confinement. Multivariate logistic regression analysis revealed that the PSA nadir was the only independent predictor of organ confinement (P = 0.044). Conclusions There was a trend that the patients with non organ-confined disease had a higher probability of PSA failure than did the patients with organ-confined disease. The PSA nadir after neoadjuvant therapy was the strongest predictor of organ confinement. The predictive value of the serum PSA nadir should be validated in well-designed larger population-based studies. [source] Role of systematic ultrasound-guided staging biopsies in predicting extraprostatic extension and seminal vesicle invasion in men with prostate cancerJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2002Koji Okihara MD Abstract Purpose To assess the presence of extraprostatic extension and seminal vesicle invasion in men with prostate cancer, we performed systematic staging biopsies targeting neurovascular bundles, seminal vesicles, and other extraprostatic tissues before the men underwent radical prostatectomy. We retrospectively evaluated the clinical efficacy of these systematic staging biopsies compared with digital rectal examination (DRE) and transrectal sonography (TRUS). Methods Two hundred forty-four candidates for prostatectomy who had a diagnostic biopsy Gleason score of 8 or higher and/or indications of extraprostatic extension (eg, seminal vesicle invasion) by DRE or TRUS underwent staging biopsies using an 18-gauge Tru-Cut needle under real-time TRUS guidance between June 1997 and March 2000. We determined the number of staging biopsy cores to be taken based on the Gleason score of the diagnostic biopsy as well as abnormal DRE and/or TRUS findings. The chi-square test was used to evaluate the statistical significance of differences. Results There were no complications of staging biopsy. In 75 (31%) of the 244 patients, results of the staging biopsies were positive. The clinical stage was upgraded by staging biopsy in 18 (24%) of these 75 patients. After the staging biopsies, 90 patients underwent radical prostatectomy. Among these 90 patients, staging biopsy specimens were positive for cancer in 20 (47%) of the 43 patients who received neoadjuvant therapy and in 1 (2%) of the 47 patients who did not receive neoadjuvant therapy. There were no false-positive staging biopsies in either group. Among the 90 patients who underwent radical prostatectomy, the false-negative rate for the prediction of organ-confined disease was 43% (30/69) for staging biopsies compared with 29% (10/34) for TRUS. The diagnostic accuracy of staging biopsies (67%; 60/90) was higher than that of DRE (52%; 47/90; p < 0.05) but lower than that of TRUS (79%; 71/90; p = 0.066). Conclusions Staging biopsies can reliably sample extraprostatic tissue, including the seminal vesicles and neurovascular bundles. Positive staging biopsy results can aid in the selection of treatment options and in the prediction of outcome for individual patients by providing definitive histologic confirmation of locally advanced disease. Conventional predictive variables for staging can be applied when the results of staging biopsies are negative. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:123,131, 2002; DOI 10.1002/jcu.10052 [source] Neoadjuvant therapy for breast cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010Stephen V. Liu MD Abstract The past few decades have seen an increase in both the role and the complexity of neoadjuvant therapy for breast cancer. Neoadjuvant therapy was initially described as systemic chemotherapy for inflammatory or locally advanced breast cancer but now entails a combination of chemotherapy, endocrine therapy, and targeted therapy. Neoadjuvant systemic therapy is employed for inoperable inflammatory and locally advanced breast cancer, and also for patients with operable breast cancers who desire breast-conserving therapy (BCT) but are not candidates based on the initial size of the tumor in relation to the size of the breast. Neoadjuvant therapy in this subset of patients may impact the surgical options. This review will summarize the benefits of neoadjuvant systemic therapy and implications for BCT, the timing of sentinel node biopsy, and the utility of magnetic resonance imaging (MRI) to predict response to therapy. J. Surg. Oncol. 2010; 101:283,291. © 2010 Wiley-Liss, Inc. [source] Esophageal cancer: Outcomes of surgery, neoadjuvant chemotherapy, and three-dimension conformal radiotherapyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2004FRCS(C), Éric Fréchette MD Abstract Neoadjuvant chemotherapy and radiation are being utilized with increasing frequency in the multimodal treatment of esophageal cancer, although their effects on morbidity, mortality, and survival remain unclear. The objective of this study was to determine the outcome of multimodal treatment in patients with localized esophageal cancer treated at a single institution. Between 1995 and 2002, 118 patients underwent treatment for localized esophageal cancer, utilizing surgery alone, chemoradiation alone, or surgery following neoadjuvant chemoradiation. There was no statistically significant difference in morbidity, mortality, or length of stay between the patients who received multimodal therapy when compared to surgery alone. A surgical resection after down-staging was possible in 9 out of 28 patients (32%) with a clinically non-resectable tumor (T4 or M1a). Forty-seven percent of the patients who received neoadjuvant therapy had a complete pathologic response with a 3-year survival of 59% as compared to only 20 months in those patients who did not achieve a complete response (P,=,0.037). Neoadjuvant chemotherapy administered concomitantly with conformal radiotherapy can be performed safely in the treatment of esophageal cancer, without increasing the operative morbidity, mortality, or length of stay. The higher complete response rates to neoadjuvant treatment (as compared to other reports) may be due to the use of three-dimensional conformal radiation therapy or the novel use of weekly carboplatin and paclitaxel. J. Surg. Oncol. 2004;87:68,74. © 2004 Wiley-Liss, Inc. [source] Management of retinoblastoma with proximal optic nerve enhancement on MRI at diagnosisPEDIATRIC BLOOD & CANCER, Issue 4 2008Saro H. Armenian DO Abstract Background In North America, retinoblastoma rarely presents with gross clinical evidence of tumor involving the optic nerve. Extent of microscopic tumor infiltration into the postlaminar optic nerve is a significant risk factor for metastasis, especially if there is tumor at the cut end. Due to poor outcomes in patients with metastatic disease, historical treatment for patients with clinical evidence of extraocular optic nerve involvement has included upfront enucleation followed by aggressive adjuvant chemotherapy. Additional orbital irradiation is advocated for individuals with optic nerve involvement at the surgical margin. Little is known about the role of neoadjuvant therapy in the setting of orbital optic nerve enhancement on magnetic resonance imaging (MRI) at diagnosis. Methods A retrospective review of consecutive retinoblastoma cases at Childrens Hospital Los Angeles over a 3-year period (2004,2006) found to have gadolinium contrast enhancement in the proximal portion of optic nerve on MRI at diagnosis. Results Nine patients fit the inclusion criteria. Two had secondary glaucoma of a sufficient degree to cause an enlarged eye (buphthalmos). Median age at presentation was 17 months (2,36 months). All patients received neoadjuvant chemotherapy prior to enucleation. Only two received external beam radiation. All are disease-free with a median follow-up of 22 months (12,41 months). Conclusions Neoadjuvant chemotherapy is well tolerated prior to enucleation of retinoblastoma-containing eyes associated with contrast enhancement of the proximal optic nerve on MRI at diagnosis. Such an approach may be used to decrease intensity or duration of chemotherapy and need for external beam radiation. Pediatr Blood Cancer 2008;51:479,484. © 2008 Wiley-Liss, Inc. [source] Outcome following surgery for squamous cell carcinoma of the oesophagusANZ JOURNAL OF SURGERY, Issue 10 2009En Loon C. Yong Abstract Introduction:, This study was undertaken to determine the outcomes of patients treated for squamous cell carcinoma (SCC) of the oesophagus. Methods:, The study group consisted of 61 patients (median age: 64 years) with invasive SCC of the oesophagus who underwent resection between 1987 and 2007 in Adelaide, South Australia. Thirty-two (52%) were female. Survival data were available for all patients. The log rank test was performed to identify prognostic factors for survival. Results:, The 5-year overall survival rate was 33% (median: 24 months). Of 61 patients, 42 (69%) received neoadjuvant therapy prior to surgery. The overall resection rate was 95%. Significant post-operative morbidity occurred in 47%, and the in-hospital mortality was 5% (30-day mortality: 3%). No overall survival benefit was seen in patients undergoing neoadjuvant therapy prior to surgical resection. However, patients who had a complete pathological response to neoadjuvant therapy had a better 5-year survival than patients who did not receive neoadjuvant therapy: 47% versus 30%, respectively. Conclusions:, Oesophagectomy following neoadjuvant therapy for SCC of the oesophagus can be performed with low perioperative mortality. A complete response to neoadjuvant therapy was followed by an improved survival outcome. [source] Oesophagectomy for tumours and dysplasia of the oesophagus and gastro-oesophageal junctionANZ JOURNAL OF SURGERY, Issue 4 2009Krishna Epari Abstract Background:, Neoadjuvant therapy, radical lymphadenectomy and treatment in high-volume centres have been proposed to improve outcomes for resectable oesophageal tumours. The aim of the present study was to review the oesophagectomy experience of a single surgeon with a moderate caseload who uses neoadjuvant therapy selectively and performs a conservative lymphadenectomy. Methods:, A retrospective review of prospectively collected data was performed. The study included 125 consecutive attempted oesophageal resections performed by a single surgeon (RC) from 1993 to 2006. Results:, All patients were staged with computed tomography and also laparoscopy for lower third and junctional tumours. Endoscopic ultrasound was used in 69%. Seventy-seven per cent were adenocarcinomas. Neoadjuvant therapy was used selectively in 23%. One hundred and twenty-one resections were carried out, giving an overall resection rate of 97% with an R0 resection in 82%. In-hospital mortality was 0.8%, clinical anastomotic leak 1.7% and median length of stay 14 days. Overall median and 5-year survival were 46 months and 47%. Stage-specific 5-year survival was 100%, 71%, 41% and 21% for stages 0, I, II and III, respectively. Isolated local recurrence occurred in 8%. Conclusions:, A moderate volume surgeon with specialist training in oesophageal resectional surgery can achieve a low mortality and anastomotic leak rate with good survival outcomes. The role for neoadjuvant therapy and radical lymphadenectomy is controversial and remains to be clearly defined. Accurate preoperative staging is essential for selection of patients for curative surgery with or without neoadjuvant therapy and for comparison of results. [source] Blood interleukin 12 as preoperative predictor of fatal postoperative sepsis after neoadjuvant radiochemotherapy,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2006A. R. Novotny Introduction: The value of preoperative whole-blood interleukin (IL) 12 levels in predicting death from postoperative sepsis was evaluated, in patients stratified by underlying malignancy, neoadjuvant tumour treatment and surgical procedure. Methods: Blood samples were collected from 1444 patients before major surgery. Whole blood was incubated with Escherichia coli lipopolysaccharide (LPS) and IL-12 production in supernatants was assessed by enzyme-linked immunosorbent assay. The prognostic impact of ability to synthesize IL-12 before surgery was investigated in patient subgroups with respect to sepsis-related mortality using multivariate binary logistic regression analysis. Results: IL-12 synthesizing capability in patients who survived sepsis was significantly higher than that in patients who developed fatal sepsis (P = 0·006). In multivariate analysis only IL-12 was associated with a lethal outcome from postoperative sepsis (P = 0·006). The prognostic impact of IL-12 was evident in patients with underlying malignancy (P = 0·011) and in those who had undergone neoadjuvant tumour treatment (P = 0·008). When patients were analysed according to the type of neoadjuvant therapy, preoperative ability to synthesize IL-12 had a significant prognostic impact in patients who had neoadjuvant radiochemotherapy (P = 0·026), but not in those who had neoadjuvant chemotherapy. Conclusion: IL-12 production after stimulation of whole blood with LPS appears to be useful for the preoperative assessment of risk of sepsis-related death after operation in patients who have undergone neoadjuvant radiochemotherapy. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high-risk, locally advanced prostate cancerCANCER, Issue 4 2009Jacqueline Vuky MD Abstract BACKGROUND: Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high-risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP). METHODS: Thirty-one patients with high-risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b-3 or serum prostate-specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER-2/neu was performed on prechemotherapy and postchemotherapy prostate tissue. RESULTS: The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty-nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI. CONCLUSIONS: No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity. Cancer 2009. © 2009 American Cancer Society. [source] |