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Preoperative Chemotherapy (preoperative + chemotherapy)
Selected AbstractsPreoperative staging and evaluation of resectability in pancreatic ductal adenocarcinomaHPB, Issue 1 2004R Andersson Background Cancer of the pancreas is a common disease, but the large majority of patients have tumours that are irresectable at the time of diagnosis. Moreover, patients whose tumours are clearly beyond surgical cure are best treated non-operatively, if possible, by relief of biliary obstruction and percutaneous biopsy to confirm the diagnosis and then consideration of oncological treatment, notably chemotherapy. These facts underline the importance of a standard protocol for the preoperative determination of operability (is it worth operating?) and resectability (is there a chance that the tumour can be removed?). Recent years have seen the advent of many new techniques, both radiological and endoscopic, for the diagnosis and staging of pancreatic cancer. It would be impracticable in time and cost to submit every patient to every test. This review will evaluate the available techniques and offer a possible algorithm for use in routine clinical practice. Discussion In deciding whether to operate with a view to resecting a pancreatic cancer, the surgeon must take into account factors related to the patient, the tumour and the institution and team entrusted with the patient's care. Patient-related factors include age, general health, pain and the presence or absence of malnutrition and an acute phase inflammatory response. Tumour-related factors include tumour size and evidence of spread, whether to adjacent organs (notably major blood vessels) or further afield. Hospital-related factors chiefly concern the volume of pancreatic cancer treated and thus the experience of the whole team. Determination of resectability is heavily dependent upon detailed imaging. Nowadays conventional ultrasonography can be supplemented by endoscopic, laparoscopic and intra-operative techniques. Computed tomography (CT) remains the single most useful staging modality, but MRI continues to improve. PET scanning may demonstrate unsuspected metastases and likewise laparoscopy. Diagnostic cholangiography can be performed more easily by MR techniques than by endoscopy, but ERCP is still valuable for preoperative biliary decompression in appropriate patients. The role of angiography has declined. Percutaneous biopsy and peritoneal cytology are not usually required in patients with an apparently resectable tumour. The prognostic value of tumour marker levels and bone marrow biopsy is yet to be established. Preoperative chemotherapy or chemoradiation may have a role in down-staging an irresectable tumour sufficiently to render it resectable. Selective use of diagnostic laparoscopy staging is potentially helpful in determination of resectability. Laparotomy remains the definitive method for determining the resectability of pancreatic cancer, with or without portal vein resection, and should be undertaken in suitable patients without clear-cut evidence of irresectability. [source] An animal model for chemotherapy-associated steatohepatitis and its prevention by the oral administration of fatty acid bile acid conjugateCANCER, Issue 1 2010Daniel Keizman MD Abstract BACKGROUND: Preoperative chemotherapy for hepatic resection of colorectal liver metastases is associated with the development of chemotherapy-associated steatohepatitis (CASH). This increases the risk of perioperative morbidity and mortality. To the authors' knowledge, an animal model for CASH has not been described previously. It has been established that fatty acid bile acid conjugates (FABACs) prevent the formation of diet-induced fatty liver. The current study was designed to establish an animal model of CASH and to use that model to study the effect of FABACs on its occurrence. METHODS: C57BL/6 mice were given different doses of oxaliplatin and irinotecan. Oxaliplatin administered once weekly at a dose of 6 mg/kg for a total dose of 24 mg/kg was tolerated best and was associated most consistently with CASH. Thus, that dose was chosen as the induction model for CASH. Subsequently, mice were divided into a control group (no treatment), an oxaliplatin group, and a CASH-prevention group, which received oxaliplatin and C20-FABAC at a dose of 150 mg/kg daily. The animals were killed after 28 days. RESULTS: Liver fat content was significantly lower (P < .0001) in the control group (51.63 mg/g) and the prevention group (62.13 mg/g) compared with the oxaliplatin group (95.35 mg/g). This difference was mainly because of the accumulation of liver triglycerides in the oxaliplatin group. CONCLUSIONS: The current results indicated that C57BL/6 mice receiving weekly oxaliplatin can be used as a model for CASH. Oral FABAC therapy reduced the development of CASH in animals that received oxaliplatin. To the authors' knowledge, this report is the first description of a model and a potential preventive treatment for CASH. Cancer 2010. © 2010 American Cancer Society. [source] Health-related quality of life during neoadjuvant treatment and surgery for localized esophageal carcinomaCANCER, Issue 9 2005Jane M. Blazeby B.Sc., M.D. Abstract BACKGROUND Esophagectomy has a negative influence on health-related quality of life (HRQL) during the first postoperative year, but it is not known how chemotherapy or chemoradiotherapy treatment before surgery affects HRQL. The current study examined HRQL during preoperative chemotherapy/chemoradiotherapy treatment and compared postoperative recovery of HRQL in patients undergoing combined treatment with patients undergoing surgery alone. METHODS One hundred three patients completed standardized HRQL measures before and during neoadjuvant treatment and before and after surgery. Mean HRQL scores were calculated and preoperative scores were used to model postoperative ratings using linear regression. RESULTS Deterioration in most aspects of HRQL occurred during preoperative chemotherapy. Patients proceeding to concomitant radiotherapy further deteriorated with specific problems with reflux symptoms and role function (difference between means >15, P < 0.01). After neoadjuvant treatment, but before surgery, HRQL returned to baseline levels. Six weeks after surgery, patients reported marked reductions in physical, role, and social function (difference between means > 30, P < 0.01) and increase in fatigue, nausea and emesis, pain, dyspnea, appetite loss, and coughing (difference between means > 15, P < 0.01). Recovery of HRQL was not hampered by preoperative treatment, and fewer problems with postoperative nausea, emesis, and dysphagia were reported by patients who had undergone neoadjuvant treatment compared with patients who had undergone surgery alone. CONCLUSIONS Preoperative chemotherapy or chemoradiotherapy had a negative impact on HRQL that was restored in patients proceeding to surgery. Recovery of HRQL after esophagectomy was not impaired by neoadjuvant treatment. These results supported the use of neoadjuvant treatment before surgery. Cancer 2005. © 2005 American Cancer Society. [source] Nephroblastoma is a success of paediatric oncologic therapy.DIAGNOSTIC CYTOPATHOLOGY, Issue 7 2010How further can we go?: Results of a cyto-histologic correlation study Abstract Nephroblastoma is a success of paediatric oncologic therapy, yet, there are still some cases where favourable response to preoperative chemotherapy is not achieved. Fine needle biopsy has the role of diagnostic confirmation and, idyllically of predicting a response to preoperative chemotherapy. To advance in this aim, we retrieved a total of 14 nephroblastomas, (seven male patients and seven female with a mean age of 44.4 months), diagnosed in our department by fine needle biopsy and submitted afterward to chemotherapy and nephrectomy, in the last 10 years. Correlation between cytologic features, (morphology, cell death, and proliferation (Ki-67 labelling index), and post chemotherapy tumour evaluation was done. Cytologic pattern per se was not predictive of histologic tumour classification (P = 0.6061). We did not find any correlation between the percentage of necrosis and apoptosis (P = 0.682) in cytologic smears and histologic regressive changes but when both these two criteria coexisted in cytologic blastemal component of nephroblastomas, this fact seemed to lead to a favourable response of the tumour to chemotherapy. When evaluation of Ki-67 labelling index was done in the blastematous component present in the smears, divergent results were obtained. The small number of cases prevented any firm conclusions. By summing up, our results support the idea that there are probably two types of blastema in nephroblastoma with different "suicide" potential and chemotherapeutic response. Further studies should be performed to stratify the influence of necrosis, apoptosis, and proliferation in chemosensivity of nephroblastomas. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Assessment of the predictive value of clinical and histopathological factors as well as the immunoexpression of p53 and bcl-2 proteins in response to preoperative chemotherapy for esophageal squamous cell carcinomaDISEASES OF THE ESOPHAGUS, Issue 3 2000J. Szumilo The aim of the study was to determine the predictive value of selected clinical and histopathological factors as well as the immunohistochemical expression of p53 and bcl-2 proteins in the prediction of the pathological response to preoperative chemotherapy in esophageal squamous cell carcinoma. Thirty-four patients with advanced squamous cell carcinoma of the thoracic esophagus (T2,4 N0,1 M0), who underwent one cycle of cisplatin and 5-fluorouracil therapy followed by subtotal esophagectomy, were studied. All clinical factors (tumor longitudinal diameter in a computed tomographic scan, invasion depth, the presence of lymph node metastasis and clinical tumor staging) were evaluated before the onset of the therapy. The histopathological features (grade of differentiation, degree of keratinization, nuclear polymorphism, mitotic index, pattern of cancer invasion and inflammatory response), and the expression of p53 and bcl-2 proteins were also estimated in prechemotherapy endoscopic biopsy specimens. Pathological response to chemotherapy was assessed in surgically resected specimens. Of 34 patients, two (5.9%) showed complete response (CR), six patients (17.6%) exhibited major histological changes (partial response 1; PR1), 24 (70.6%) showed minor histological changes (partial response 2; PR2), and two patients (5.9%) exhibited no response to chemotherapy (stable disease; SD). There were no significant relationships between the response to preoperative chemotherapy (CR + PR1 vs. PR2 + SD) and the majority of the clinical and all the histopathological features. Deeper cancer invasion before chemotherapy was the only factor that tended to worsen the therapy effect (p < 0.01). The pathological response to treatment had no significant associations with the expression of p53 and bcl-2 proteins in esophageal squamous cell carcinoma. It should be noted, however, that both patients in CR were p53 and bcl-2 protein-negative. [source] The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Katja Ott Abstract We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10- methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients. © 2006 Wiley-Liss, Inc. [source] Expression profiling of Wilms tumors reveals new candidate genes for different clinical parametersINTERNATIONAL JOURNAL OF CANCER, Issue 8 2006B. Zirn Abstract Wilms tumor is the most frequent renal neoplasm in children, but our understanding of its genetic basis is still limited. We performed cDNA microarray experiments using 63 primary Wilms tumors with the aim of detecting new candidate genes associated with malignancy grade and tumor progression. All tumors had received preoperative chemotherapy as mandated by the SIOP protocol, which sets this study apart from related approaches in the Unites States that are based on untreated samples. The stratification of expression data according to clinical criteria allowed a rather clear distinction between different subsets of Wilms tumors. Clear-cut differences in expression patterns were discovered between relapse-free as opposed to relapsed tumors and tumors with intermediate risk as opposed to high risk histology. Several differentially expressed genes, e.g.TRIM22, CENPF, MYCN, CTGF, RARRES3 and EZH2, were associated with Wilms tumor progression. For a subset of differentially expressed genes, microarray data were confirmed by real-time RT-PCR on the original set of tumors. Interestingly, we found the retinoic acid pathway to be deregulated at different levels in advanced tumors suggesting that treatment of these tumors with retinoic acid may represent a promising novel therapeutic approach. © 2005 Wiley-Liss, Inc. [source] Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2006Hong-Bing Cai Abstract Aim:, To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix. Methods:, From January 1999 to December 2001, 106 women with cervical cancer stage IB received neoadjuvant chemotherapy (n = 52) or primary surgery (n = 54). These were randomly assigned. Clinical effects and pathological changes were simultaneously recorded. Results:, The overall clinical response rate was 84.6% and included a complete response (CR) in four patients (7.7%), partial response (PR) in 40 patients (76.9%), and stable disease (SD) in the remaining eight patients (15.4%). Surgery revealed positive nodes in 9.6% neoadjuvant chemotherapy group patients and in 29.6% primary surgery group patients (P = 0.014). Similar results occurred with vascular space involvement: 27.8% in the primary surgery group compared to 9.6% in the neoadjuvant chemotherapy group (P = 0.024). However, parametrial infiltration was found in 7.4% of the patients in the primary surgery group, while only 3.8% showed it in the neoadjuvant chemotherapy group (P = 0.679). The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy (84.6%) than for the control group (75.9%) (P = 0.0112). The median survival time in patients with complete response and partial response to chemotherapy (83.3 months) was significantly higher than that of patients with stable disease to chemotherapy (55.2 months) (P = 0.0049). 27.3% of patients developed recurrent disease within 5 years of the primary treatment. The women with recurrence included partial response in six patients (60.0%), and stable disease in four patients (40.0%). For the other patients there was partial response and complete response in 38 patients (90.5%), and stable disease in the remaining four patients (9.5%) (P = 0.035). Conclusion:, Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer. [source] Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug deliveryJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2002Eugene P. Goldberg The recent literature documents the growing interest in local intratumoral chemotherapy as well as systemic preoperative chemotherapy with evidence for improved outcomes using these therapeutic modalities. Nevertheless, with few exceptions, the conventional wisdom and standard of care for clinical and surgical oncology remains surgery followed by radiation and/or systemic chemotherapy, as deemed appropriate based on clinical findings. This, in spite of the fact that the toxicity of conventional systemic chemotherapy and immunotherapy affords limited effectiveness and frequently compromises the quality of life for patients. Indeed, with systemic chemotherapy, the oncologist (and the patient) often walks a fine line between attempting tumour remission with prolonged survival and damaging the patient's vital functions to the point of death. In this context, it has probably been obvious for more than 100 years, due in part to the pioneering work of Ehrlich (1878), that targeted or localized drug delivery should be a major goal of chemotherapy. However, there is still only limited clinical use of nonsystemic intratumoral chemotherapy for even those high mortality cancers which are characterized by well defined primary lesions i.e. breast, colorectal, lung, prostate, and skin. There has been a proliferation of intratumoral chemotherapy and immunotherapy research during the past two to three years. It is therefore the objective of this review to focus much more attention upon intratumoral therapeutic concepts which could limit adverse systemic events and which might combine clinically feasible methods for localized preoperative chemotherapy and/or immunotherapy with surgery. Since our review of intratumoral chemo-immunotherapy almost 20 years ago (McLaughlin & Goldberg 1983), there have been few comprehensive reviews of this field; only one of broad scope (Brincker 1993), three devoted specifically to gliomas (Tomita 1991; Walter et al. 1995; Haroun & Brem 2000), one on hepatomas (Venook 2000), one concerning veterinary applications (Theon 1998), and one older review of dermatological applications (Goette 1981). However, none have shed light on practical opportunities for combining intratumoral therapy with subsequent surgical resection. Given the state-of-the-art in clinical and surgical oncology, and the advances that have been made in intratumoral drug delivery, minimally invasive tumour access i.e. fine needle biopsy, new drugs and drug delivery systems, and preoperative chemotherapy, it is timely to present a review of studies which may suggest future opportunities for safer, more effective, and clinically practical non-systemic therapy. [source] Current neoadjuvant strategies in rectal cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010Lucas A. Julien MD Abstract Treatment modalities in rectal cancer have undergone a slow, evolutionary transition over the past 30 years. More recently, contemporary descriptions of advanced preoperative chemotherapy and radiation schema have led to a rapid revolution in the management of this disease. In this review we focus on current evidence-based neoadjuvant strategies used in the treatment of locally advanced rectal cancer and metastatic rectal disease. Finally, we provide a foundation for discussion of still unresolved issues. J. Surg. Oncol. 2010; 101:321,326. © 2010 Wiley-Liss, Inc. [source] Trastuzumab in Primary Inflammatory Breast Cancer (IBC): High Pathological Response Rates and Improved OutcomeTHE BREAST JOURNAL, Issue 5 2010Shaheenah Dawood MRCP (UK) Abstract:, Inflammatory breast cancer (IBC) represents a rare but aggressive and lethal form of locally advanced breast cancer (LABC) and frequently with HER-2 neu overexpressed or amplified. We retrospectively identified 16 newly diagnosed HER-2/neu-positive IBC patients who were treated with preoperative trastuzumab. We determined the pathological complete response rate (pCR) when trastuzumab was added to preoperative chemotherapy in patients with HER2/neu-positive IBC. Furthermore, we assessed the expression of CXCR4 in metastatic recurrence sites. Ten patients (62.5%) achieved a pCR. Six patients (37.5%) achieved a partial response. Median follow-up of all patients was 24.2 months. Four (25%) patients have experienced a progression, of which three were in the brain. Two-year progression-free survival was 59.4% (95% CI 35,100). High expression of CXCR4 was detected in the brain metastases. We conclude that in spite of high pCR rates among women with HER-2/neu-positive IBC treated with neoadjuvant trastuzumab-based regimens the outcome remains dismal and brain recurrences are frequent. CXCR4 may represent a novel therapeutic target. [source] Optimal duration of preoperative anti-helminthic therapy for pulmonary hydatid surgeryANZ JOURNAL OF SURGERY, Issue 5 2010Parvaiz A. Koul Abstract Background:, The optimal duration of preoperative anti-helminths for prevention of recurrences in pulmonary hydatidosis is unclear, although 1,3 weeks of therapy is routinely used. Methods:, Forty-five patients of pulmonary hydatid disease were randomly assigned into four groups to receive either 0, 2, 4 or 8 weeks of preoperative albendazole (ABZ) and praziquantel (PZQ). Viability of the scolices in the fluid harvested at surgery (methylene blue staining) and ability to produce peritoneal hydatids in mice (intra-peritoneal inoculation) were compared in different groups. Results:, The percentage viability of the scolices as a whole was significantly (P < 0.001) lower in the treated cysts (n= 36, mean 43.5 ± 35.69) compared with the untreated cysts (n= 8, mean 94.75 ± 7.21). The viability progressively decreased with increasing durations of chemotherapy (P < 0.001). Mean percentage viability of scolices was 88.72 ± 4.91% in patients treated for 2 weeks (n= 12), 38.09 ± 9.10% after 4 weeks (n= 11) and 8.1 ± 9.23% after 8 weeks (n= 14). Intra-peritoneal mice inoculation was positive in 90% of the cysts that received therapy for 2 weeks or less and none of the patients who received therapy for 8 weeks had a positive inoculation. Conclusions:, Preoperative combination therapy with ABZ and PZQ effects a scolicidal response which increases with the increasing duration of the preoperative chemotherapy, and a 4-week course of the combination chemotherapeutic agents seems to be the minimum required duration for ensuring scolicidal activity enough to prevent spillage-induced recurrences following pulmonary hydatidosis. [source] Resection of liver metastases from colorectal cancer: does preoperative chemotherapy affect the accuracy of PET in preoperative planning?ANZ JOURNAL OF SURGERY, Issue 5 2009Sam Adie Abstract Background:, Preoperative scanning for hepatic colorectal metastases surgery remains a challenge, especially in the age of preoperative chemotherapy, which has marked biochemical and physical effects on the liver. Integrated fluoro-deoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) has applications for detecting extrahepatic disease. The aim of the present study was to investigate FDG-PET/CT as a preoperative planning tool for detecting liver lesions in patients with and without preoperative chemotherapy. Methods:, Patients who had resection of hepatic colorectal metastases between January 2004 and June 2006 were included. Patients were divided into those who received preoperative chemotherapy and those who did not. Malignant hepatic lesions found on each scan were compared with those found on histopathology, intraoperative examination and/or intraoperative ultrasound. Accurate scans (scan lesions corresponded to true lesions), false positives (scan lesions detected at least one non-lesion) and false negatives (scan lesions missed at least one true lesions) were recorded. Results were also compared on a per lesion basis. Results:, A total of 21 patients had preoperative FDG-PET/CT scans with preoperative chemotherapy and 53 without. Accurate tests were six (29%) for the chemotherapy group versus 28 (53%) for the non-chemotherapy group (P= 0.06). Notably, there were 11 (52%) underestimations in the chemotherapy group versus 18 (34%) in the non-chemotherapy group. A total of 1.7 lesions were missed per patient in the chemotherapy group versus 0.7 in those who did not receive chemotherapy. Conclusion:, Preoperative assessment with FDG-PET/CT is not useful for hepatic colorectal metastases, particularly when preoperative chemotherapy is used, with a trend towards underestimation of lesions. [source] Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2009T. Yoshikawa Background: Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma. Methods: Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m2 on days 1 and 15) and cisplatin (80 mg/m2 on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death. Results: The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14·6 months and the 3-year survival rate 27 per cent. Conclusion: This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [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] Histologic changes associated with false-negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node-positive breast cancer before treatmentCANCER, Issue 12 2010Alexandra S. Brown MD Abstract BACKGROUND: A wide range of false-negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node-positive disease before treatment. METHODS: Eighty-six patients with confirmed lymph node-positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin-stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated. RESULTS: Forty-seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false-negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true-negative SLNs and in only 2 (18%) of 11 patients with false-negative SLNs (P = .03, Fisher exact test, 2-tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false-negative SLN of 82% and 65%, respectively. CONCLUSIONS: Absence of treatment effect in SLNs after chemotherapy in patients with lymph node-positive disease at initial presentation has good sensitivity but low specificity for identifying a false-negative SLN. Cancer 2010. © 2010 American Cancer Society. [source] Early 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography may identify a subset of patients with estrogen receptor-positive breast cancer who will not respond optimally to preoperative chemotherapyCANCER, Issue 4 2010Andrea A. Martoni MD Abstract BACKGROUND: A pathologic complete response (pCR) and minimal residual disease (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced breast cancer (BC) correlates with a good prognosis. METHODS: Patients who received from 6 to 8 cycles of PCT for BC were monitored by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET), and the maximal standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles, after 4 cycles, and at the end of PCT. SUVmax percentage changes (,-SUV) were compared with the pathologic response rate. Patients who had a pCR or pMRD in the tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were defined as having obtained an optimal pathologic response (pR), whereas all the other conditions were classified as a pathologic nonresponse (pNR). RESULTS: Of 34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had pMRD). After the second cycle, the ,-SUV threshold with optimal negative predictive value to predict a pR was 50%. Twenty-six patients (76%) had a ,-SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR. Conversely, all 8 patients who had a ,-SUV ,50% had a pNR. All 8 of those patients had estrogen recepetor-positive tumors. CONCLUSIONS: Early evaluation of metabolic response by 18F-FDG-PET during PCT was able to identify 30% of patients, all with estrogen receptor-positive tumors, who would not obtain pR after completion of chemotherapy program. Cancer 2010. © 2010 American Cancer Society. [source] Health-related quality of life during neoadjuvant treatment and surgery for localized esophageal carcinomaCANCER, Issue 9 2005Jane M. Blazeby B.Sc., M.D. Abstract BACKGROUND Esophagectomy has a negative influence on health-related quality of life (HRQL) during the first postoperative year, but it is not known how chemotherapy or chemoradiotherapy treatment before surgery affects HRQL. The current study examined HRQL during preoperative chemotherapy/chemoradiotherapy treatment and compared postoperative recovery of HRQL in patients undergoing combined treatment with patients undergoing surgery alone. METHODS One hundred three patients completed standardized HRQL measures before and during neoadjuvant treatment and before and after surgery. Mean HRQL scores were calculated and preoperative scores were used to model postoperative ratings using linear regression. RESULTS Deterioration in most aspects of HRQL occurred during preoperative chemotherapy. Patients proceeding to concomitant radiotherapy further deteriorated with specific problems with reflux symptoms and role function (difference between means >15, P < 0.01). After neoadjuvant treatment, but before surgery, HRQL returned to baseline levels. Six weeks after surgery, patients reported marked reductions in physical, role, and social function (difference between means > 30, P < 0.01) and increase in fatigue, nausea and emesis, pain, dyspnea, appetite loss, and coughing (difference between means > 15, P < 0.01). Recovery of HRQL was not hampered by preoperative treatment, and fewer problems with postoperative nausea, emesis, and dysphagia were reported by patients who had undergone neoadjuvant treatment compared with patients who had undergone surgery alone. CONCLUSIONS Preoperative chemotherapy or chemoradiotherapy had a negative impact on HRQL that was restored in patients proceeding to surgery. Recovery of HRQL after esophagectomy was not impaired by neoadjuvant treatment. These results supported the use of neoadjuvant treatment before surgery. Cancer 2005. © 2005 American Cancer Society. [source] Lack of association between amplification of her-2 and response to preoperative taxanes in patients with breast carcinomaCANCER, Issue 2 2004Ana M. Gonzalez-Angulo M.D. Abstract BACKGROUND The objective of the current study was to determine whether her-2 amplification was associated with a pathologic response to preoperative chemotherapy with taxanes in patients with early-stage breast carcinoma. METHODS The authors evaluated 71 patients treated for AJCC Stage II and III breast carcinoma with preoperative taxanes whose tissue specimens were still available. Fifty-seven patients (80%) had received paclitaxel and 14 (20%) had received docetaxel (4 cycles of either drug). Amplification of the her-2 gene was determined using fluorescence in situ hybridization. RESULTS The median patient age was 49 years (range, 21,70 years). Forty-eight patients (68%) had Stage II breast carcinoma and 23 (32%) had Stage III disease. her-2 gene amplification was detected in 19 tumor specimens (28%). Hormone receptors (estrogen and/or progesterone) were detected in 11 her-2,positive tumor specimens (58%) and in 31 her-2,negative tumor specimens (85%). Eight pathologic complete responses (pCR; breast and axillary lymph nodes) occurred, 3 (16%) in patients with her-2,positive tumor specimens and five (10%) in patients with her-2,negative tumor specimens (P = 0.68). Twelve patients achieved pCR in the breast, 5 (26%) in patients with her-2,positive tumors and 7 (15%) in patients with her-2,negative tumors (P = 0.3). At a median follow-up of 61 months, none of the patients with a pCR developed recurrent disease, regardless of their her-2 status. The progression-free and overall survival rates were similar in both HER-2,positive and her-2,negative groups (P = 0.45 and P = 0.14, respectively). CONCLUSIONS her-2 gene amplification was not found to be predictive of a pathologic response to preoperative taxanes in patients with early-stage breast carcinoma. Cancer 2004. © 2004 American Cancer Society. [source] HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic processCANCER, Issue 8 2002Anne Vincent-Salomon M.D. Abstract BACKGROUND The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process. METHODS HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post-CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2,T4,N1,N2 breast carcinoma and were treated by preoperative anthracycline-based CT and then underwent surgery. The second group included 44 patients with metastatic breast carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2 status was determined by immunohistochemistry using an anti-p185HER/neu monoclonal antibody and was classified as overexpressed or not overexpressed. RESULTS Among the patients who received preoperative CT, HER2 overexpression was observed in 15 of 59 patients (25%). A complete pathologic response was observed in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining residual tumors and was no longer detectable in 2 tumors. In addition, the 29 tumors with no HER2 overexpression before CT remained negative after treatment. In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two patients who had low levels of HER2 overexpression in their primary tumors, no staining was observed in the secondary tumor (one pulmonary tumor and one liver tumor). There were no tumors in which the overexpression of HER2 was found only in the metastasis. CONCLUSIONS The current study showed that, in most patients, HER2 overexpression was unchanged after CT and in metastatic sites. No HER2 negative primary tumors became HER2 positive after patients received CT or during the metastatic process. In a few patients, a diminution in the level of HER2 expression was observed after CT or in secondary tumors. This may have been due to a transitory state of altered tumor cells or to the selection of HER2 negative tumor cells clones. Cancer 2002;94:2169,73. © 2002 American Cancer Society. DOI 10.1002/cncr.10456 [source] | |||||||||||||||||||||||||