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Results for “Neoadjuvant Therapy”

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PubMed2006

Blood interleukin 12 as preoperative predictor of fatal postoperative sepsis after neoadjuvant radiochemotherapy.

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.

Biomarkers↗

PubMedDate not supplied

Neoadjuvant chemoradiotherapy is not associated with a higher complication rate vs. surgery alone in patients undergoing esophagectomy.

Recent studies have claimed a higher rate of perioperative complications related to the use of neoadjuvant chemoradiotherapy in the treatment of esophageal cancer. We tested the hypothesis that neoadjuvant chemoradiotherapy has no significant effect on the perioperative complication rate. Data on 155 patients with esophageal carcinoma treated between 1996 and 2001 were collected in a prospective database. This included 61 patients (40%) treated with neoadjuvant chemoradiotherapy (group I) and 94 patients (60%) who underwent esophagectomy alone (group II). Neoadjuvant therapy consisted of two courses of cisplatinum and continuous-infusion 5-fluorouracil with radiation followed by esophagectomy. Ivor-Lewis esophagectomy was performed in 146 (94%) and a transhiatal resection in nine (6%). The two groups (I vs. II) were comparable in terms of age (61.3+/-11 years vs. 64.8+/-11 years), diagnosis (adenocarcinoma: 82% vs. 83%; squamous cell carcinoma:11% vs. 16%), and stage (stage 0 to I: 39% vs. 38%; stage II: 25% vs. 34%; stage III: 30% vs. 24%; and stage IV: 6% vs. 4%). The neoadjuvant group had 23 complete responses, 11 partial responses, and 27 nonresponses. There were 39 complications (25.1%) for the cohort, which included three deaths (1.9%) and four anastomotic leaks (2.6%) demonstrated by Gastrografin swallow (1 in group I vs. 3 in group II. Only one leak required reoperation (group II); all others responded to conservative treatment. Group I had 14 complications (22.9%) vs. 25 (26.5%) in group II (P=NS). Groups were comparable with respect to the rate of pulmonary events (4.9% vs. 6.3%), arrhythmias (6.5% vs. 8.5%), and stricture formation (6.5% vs. 7.4%). Neoadjuvant chemoradiotherapy in patients with esophageal cancer was not associated with increased perioperative morbidity or mortality. Complete response to chemoradiotherapy also did not affect the complication rate (26% vs. 22%).

Adenocarcinoma↗

PubMed2005

Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial.

BACKGROUND: Some oestrogen-receptor (ER) positive breast cancers express epidermal growth factor receptor (EGFR), but whether inhibition of EGFR can suppress proliferation of breast cancer cells and ER function is not known. METHODS: In a double-blind, placebo-controlled randomised trial of 56 postmenopausal patients with ER-positive and EGFR-positive primary breast cancer, 27 women were randomly assigned to the tyrosine-kinase inhibitor of EGFR gefitinib (250 mg given orally once a day) and the aromatase inhibitor anastrozole (1 mg given orally once a day), and 29 women to gefitinib (250 mg given orally once a day) and placebo of identical appearance to anastrozole given orally once a day, all given for 4-6 weeks before surgery. Primary outcome was inhibition of tumour-cell proliferation, as measured by Ki67 antigen labelling index. Secondary outcomes were reduction in EGFR phosphorylation at Tyr 845, reduction in ER phosphorylation at Ser 118, tumour size, and toxic effects. Analyses were by intention to treat. FINDINGS: Patients assigned gefitinib and anastrozole had a greater reduction from pretreatment values in proliferation-related Ki67 labelling index than did those assigned gefitinib alone (mean % reduction 98.0 [95% CI 96.1-98.9] vs 92.4 [85.1-96.1]; difference between groups 5.6% [5.1-6.0], p=0.0054). Tumour size was reduced by 30-99% (partial response) in 14 of 28 patients assigned gefitinib and [corrected]in 12 of 22 assigned gefitinib, as assessed by ultrasonography. Reduction in phosphorylation of ER at Ser 118 was similar for both groups. Treatment was well tolerated and much the same for both groups. INTERPRETATION: Single-agent gefitinib and gefitinib combined with anastrozole are well-tolerated and effective treatments for reducing the size of breast tumours and levels of ER phosphorylation when given as neoadjuvant therapy.

Anastrozole↗

PubMed2004

A phase II trial of neoadjuvant docetaxel and capecitabine for locally advanced breast cancer.

PURPOSE: This study evaluated the toxicity and efficacy of docetaxel/capecitabine as neoadjuvant treatment for stage 2/3 breast cancer. EXPERIMENTAL DESIGN: Subjects with newly diagnosed invasive stage 2 and 3 breast cancer were eligible. The first cohort of patients was treated at dose A with neoadjuvant docetaxel (75 mg/m(2) i.v. day 1) and capecitabine (1000 mg/m(2) orally twice daily days 2-15) for four cycles. A second cohort of subjects was treated with a reduced dose, dose B, of docetaxel (60 mg/m(2) i.v. day 1) and capecitabine (937.5 mg/m(2) orally twice daily days 2-15). RESULTS: Thirty patients were enrolled. Eight of 10 patients treated at dose A required dose reductions of either docetaxel or capecitabine secondary to grade 3 or 4 toxicities: mucositis (1), hand-foot syndrome (3), diarrhea (2), perirectal abscess (1), and neutropenia (2). Because of a high rate of dose reductions, the next 20 patients were treated at dose B. The mean cumulative administered dose of docetaxel was 285 and 231 mg/m(2) at dose A and dose B, respectively. For capecitabine, the mean cumulative dose at dose A and B were similar at 1585 and 1627 mg/m(2)/day, respectively. The overall clinical response rate was 90% with 31% of patients having a complete response and 59% having a partial response. A pathological complete response in the breast was achieved in 10% of patients after four cycles of docetaxel/capecitabine. CONCLUSIONS: Docetaxel/capecitabine is a highly active regimen in the neoadjuvant setting. Neoadjuvant therapy with 75 mg/m(2) docetaxel and 1600 mg/m(2)/day days 2-15 is recommended.

Administration, Oral↗

PubMed2006

Ductal access for prevention and therapy of mammary tumors.

In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraductally administered anticancer agents 4-hydroxytamoxifen and pegylated liposomal doxorubicin (PLD) in the prevention and treatment of breast cancer using the rat N-methyl-N'-nitrosourea-induced and spontaneous HER-2/neu transgenic mouse (neu-N) models of breast cancer. Intraductal administration of PLD to neu-N mice caused regression of established tumors and prevented tumor development more effectively than i.v. injection (P < 0.0001). Intraductal administration resulted in lower circulating levels of PLD compared with i.v. administration, with no evidence of systemic toxicity or long-term histopathologic changes in the mammary gland. Compared with systemic administration, intraductal injection provides direct access to breast lesions with higher local and lower systemic drug exposure. These studies suggest that this approach has potential for application to prevention and neoadjuvant therapy of early breast cancer.

Animals↗

PubMed2006

Imaging before and after multimodal treatment for malignant pleural mesothelioma.

PURPOSE: Computed tomography (CT), magnetic resonance (MR) and positron emission tomography (PET) have a very important role in the diagnosis of malignant pleural mesothelioma (MPM) in the choice of chemoradiotherapy alone or in combination with surgery and in evaluating possible recurrence. It is also essential for assessing the possible benefits of radical surgery (pleuropneumonectomy) in terms of patient survival. MATERIALS AND METHODS: We considered 28 patients suffering from MPM whose mean survival after diagnosis was 15-18 months. Sixteen of these patients had radiotherapy or chemoradiotherapy alone, according to standard protocols, while 12 also underwent surgery. The CT features of MPM were thoroughly examined, as was the role of PET and CT-PET in achieving accurate disease staging and consequent selection of candidates for surgery. RESULTS: Nine of the 12 patients who underwent pleuropneumonectomy had no significant survival advantage over the mean survival in the 16 who were not operated whereas the other three lived 1-3 years longer. Two patients underwent surgery after an optimal response to chemoradiotherapy, but both survived less than a year due to particularly aggressive recurrences. CONCLUSIONS: CT, PET and CT-PET are indicated for diagnosis and, above all, for staging of MPM, in the selection of patients who might benefit from surgery after neoadjuvant therapy and also in identifying small recurrences and/or remote metastases. Being highly specific, PET is essential in the follow-up of patients undergoing chemoradiotherapy alone and/or surgery. Each imaging modality has its advantages and limitations, but their combined use is crucial in determining the most appropriate treatment options for patients with MPM.

Chemotherapy, Adjuvant↗

PubMed2006

Molecular responses of rectal cancer to preoperative chemoradiation.

BACKGROUND AND PURPOSE: Some rectal cancers respond well to preoperative neoadjuvant therapy while others are inherently resistant or develop resistance during the treatment. To understand the mechanism underlying these differences, several markers that might be prognostic or predictive of downstaging in response to chemoradiotherapy in patients with rectal cancer were evaluated. MATERIAL AND METHODS: Thirty patients were enrolled in this study. All were treated with preoperative chemoradiation (45Gy in 25 fractions+5-FU). Paraffin-embedded sections obtained before and after therapy were stained by H&E, for COX-2, and Ki67. In addition, osteopontin and IL-6 concentrations were determined in blood samples obtained before, during, and after therapy. RESULTS: COX-2 expression increased in 67% (n=8/12) of the patients from a median of 0% before to 74% after therapy (p=0.009). Ki67 median positivity diminished from 90% to 45% in 83% (n=10/12) of cases (p=0.007). Osteopontin expression showed no significant changes during therapy, whereas IL-6 expression levels increased in 70% (n=19/27) of all patients (p<0.001). For osteopontin and IL-6, patients with a complete response tended to have lower pre-therapy levels. Moreover, osteopontin was much higher before (p=0.02) and after therapy (p=0.01) in patients who later developed metastases. CONCLUSIONS: Chemoradiotherapy seems to affect expression of COX-2 and Ki67 which indicates that these proteins might be of importance in predicting long-term outcome. Moreover, osteopontin might be a marker of metastases.

Adult↗

PubMed2000

Locally advanced breast cancer and postmastectomy radiotherapy.

Most patients with locally advanced breast cancer should be treated with a combination of chemotherapy, mastectomy (with immediate reconstruction if the patient so desires), and radiotherapy. Nonetheless, it seems reasonable to offer breast-conserving treatment to selected individuals who respond well to neoadjuvant therapy. Postmastectomy radiotherapy clearly reduces the risk of local-regional and distant failure for patients with earlier-stage invasive breast cancer with involved axillary lymph nodes. Certain subgroups of patients, however, may have such low local-regional failure rates that patients will not routinely find the benefits of radiotherapy sufficient to undergo such treatment. Further investigation of this issue is needed.

Breast Neoplasms↗

PubMed2006

Monitoring therapeutic efficacy in breast carcinomas.

The aim of imaging during and after neoadjuvant therapy is to document and quantify tumor response: has the tumor size been accurately measured? Certainly, the most exciting information for the oncologists is: can we identify good or nonresponders, and can we predict the pathological response early after the initiation of treatment? This review article will discuss the role and the performance of the different imaging modalities (mammography, ultrasound, magnetic resonance imaging and FDG-PET imaging) for evaluating this therapeutic response. It is important to emphasize that, at this time, clinical examination and conventional imaging (mammography and ultrasound) are the only methods recognized by the international criteria. Magnetic resonance imaging and FDG-PET imaging are very promising for predicting the response early after the initiation of neoadjuvant chemotherapy.

Breast Neoplasms↗

PubMed2001

Issues involved in research into the neoadjuvant treatment of breast cancer.

Randomized studies have failed to find convincing evidence that neo-adjuvant chemotherapy results in improved overall survival. This may be related to limited efficacy of the regimens used. A sequence of an anthracycline-based primary chemotherapy followed by docetaxel has shown promising results which are briefly discussed. The assessment of the efficacy of neoadjuvant therapy should be based on the evaluation of pathological response and a simple, reproducible method of grading differential response would be of great value. Positive identification of tumor stroma is essential in defining pathological complete response (pCR). This paper presents a grading scheme based purely on microscopic assessment which classifies patients into five groups with significantly different disease-free and overall survival. A system dividing patients into only two groups, i.e. those with pCR or those with any evidence of invasive tumor, may lose information of prognostic value. Assessing the response of metastatic disease in the lymph nodes, as well as response of the primary tumor, may further refine our ability to identify those patients likely to gain most from neoadjuvant chemotherapy.

Antineoplastic Agents, Phytogenic↗

PubMed2002

Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer.

BACKGROUND: After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy. METHODS: Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection. RESULTS: SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%. CONCLUSIONS: SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.

Adult↗

PubMed2003

Neoadjuvant treatment with weekly high-dose 5-Fluorouracil as 24-hour infusion, folinic acid and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer.

PURPOSE: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC). PATIENTS AND METHODS: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m(2) FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m(2 ) 5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up. RESULTS: After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3-4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12-38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%. CONCLUSION: The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.

Aged↗

PubMed2005

Aromatase inhibitors: cellular and molecular effects.

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

Anastrozole↗

PubMed2002

[Treatment of pancreatic adenocarcinoma].

Better results of resections for pancreatic adenocarcinoma are reported in published data from 1990: 1. the lower mortality rate is probably not the only reason why these results are better; 2. the palliative resections rate seem to be lower (as the rates of exploratory laparotomies and by-pass procedures); 3. the impact of resection's quality on the results is difficult to demonstrate and the benefit of extended lymphadenectomy remains unclear; 4. moreover, in recent published series, many patients had adjuvant or neoadjuvant therapy, but often in uncontrolled studies. Multimodality treatment is probably useful for better local control and better disease free survival; this therapeutic approach is widely used today but the results remain to be confirmed by clinical trials. Unfortunately, 90% of the patients had locally advanced or metastatic disease at the time of diagnosis; in these patients clinical research is a challenge in order to change the prognosis; actually, epidemiological studies are still showing that quite all the patients die.

Adenocarcinoma↗

PubMed2004

Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging?

In rectal cancer, preoperative staging should identify early tumours suitable for treatment by surgery alone and locally advanced tumours that require therapy to induce tumour regression from the potential resection margin. Currently, local staging can be performed by digital rectal examination (DRE), endoluminal ultrasound (EUS) or magnetic resonance imaging (MRI). Each staging method was compared for clinical benefit and cost-effectiveness. The accuracy of high-resolution MRI, DRE and EUS in identifying favourable, unfavourable and locally advanced rectal carcinomas in 98 patients undergoing total mesorectal excision was compared prospectively against the resection specimen pathological as the gold standard. Agreement between each staging modality with pathology assessment of tumour favourability was calculated with the chance-corrected agreement given as the kappa statistic, based on marginal homogenised data. Differences in effectiveness of the staging modalities were compared with differences in costs of the staging modalities to generate cost effectiveness ratios. Agreement between staging and histologic assessment of tumour favourability was 94% for MRI (kappa=0.81, s.e.=0.05; kappa(W)=0.83), compared with very poor agreements of 65% for DRE (kappa=0.08, s.e.=0.068, kappa(W)=0.16) and 69% for EUS (kappa=0.17, s.e.=0.065, kappa(W)=0.17). The resource benefits resulting from the use of MRI rather than DRE was 67164 UK pounds and 92244 UK pounds when MRI was used rather than EUS. Magnetic resonance imaging dominated both DRE and EUS on cost and clinical effectiveness by selecting appropriate patients for neoadjuvant therapy and justifies its use for local staging of rectal cancer patients.

Adult↗

PubMedDate not supplied

Pancreaticoduodenectomy in the presence of superior mesenteric venous obstruction.

The study goal was to determine the technical feasibility and outcomes associated with pancreaticoduodenectomy for periampullary malignancies with near (>80%) or complete (100%) superior mesenteric venous (SMV) obstruction. A retrospective examination of 11 patients with high-grade or complete SMV obstruction who underwent pancreaticoduodenectomy at five academic medical centers is reviewed. Pancreaticoduodenectomy for locally advanced periampullary malignancies causing high-grade or complete SMV obstruction is technically feasible. Operative approaches and outcomes are presented. One 30-day death was observed. Median survival of the cohort is 18 months. Survivals exceeding 2 years post-resection have been observed. In a number of cases, significant palliation of pain and of biliary and duodenal obstruction were achieved. Based on this initial series, pancreaticoduodenectomy in the presence of near or total SMV obstruction is feasible, may result in an R0 resection, and may be beneficial in select patients with a periampullary malignancy. We suggest such an approach be considered particularly following completion of neoadjuvant therapy without systemic progression. Further studies and more long-term follow-up at high-volume centers are required, however, to better determine the indications and potential benefit of such an undertaking.

Aged↗

PubMed1998

Short-course induction chemoradiotherapy with paclitaxel for stage III non-small-cell lung cancer.

BACKGROUND: This study assessed toxicity, tumor response, disease control, and survival after short-course induction chemoradiotherapy and surgical resection in patients with stage III non-small-cell lung carcinoma. METHODS: Forty-five patients with stage III non-small-cell lung carcinoma received 12-day induction therapy of a 96-hour continuous infusion of cisplatin (20 mg/m2 per day), 24-hour infusion of paclitaxel (175 mg/m2), and concurrent accelerated fractionation radiation therapy (1.5 Gy twice daily) to a dose of 30 Gy. Surgical resection was scheduled for 4 weeks later. Postoperatively, a second identical course of chemotherapy and concurrent radiation therapy (30 to 33 Gy) was given. RESULTS: Induction toxicity resulted in hospitalization of 18 (40%) patients for neutropenic fever. No induction deaths occurred. Of 40 (89%) patients who underwent thoracotomy, resection for cure was possible in 32 (71%) patients. Pathologic response was noted in 21 (47%) patients, and 14 (31%) were downstaged to mediastinal node negative (stage 0, I, or II). At a median follow-up of 19 months, 24 patients were alive, 10 with recurrent disease. Of 21 deaths, 16 were from recurrent disease, three were from treatment, and two were unrelated. Recurrent disease was distant in 21 patients, distant and locoregional in 2, and locoregional in 3. The Kaplan-Meier projected 24-month survival is 49%. Projected 24-month survival is 61% for stage IIIA, 17% for stage IIIB (p = 0.035); 84% for pathologic responders, 22% for nonresponders (p<0.001); 83% for downstaged patients (stage 0, I, or II), 33% for those not downstaged (p = 0.005); and 63% for resectable patients, 14% for unresectable patients (p = 0.007). CONCLUSIONS: We conclude that short-course neoadjuvant therapy with paclitaxel (1) has manageable toxicity and a low treatment mortality, (2) results in good tumor response and downstaging, (3) provides excellent locoregional control with most recurrences being distant, and (4) has improved the median survival compared with historical controls. Survival was better in stage IIIA patients, resectable patients, pathologic responders, and patients downstaged to mediastinal node negative disease (stage 0, I, or II).

Antineoplastic Agents, Phytogenic↗

PubMed2005

Histomorphologic tumor regression and lymph node metastases determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer: implications for response classification.

OBJECTIVE: We sought to quantitatively and objectively evaluate histomorphologic tumor regression and establish a relevant prognostic regression classification system for esophageal cancer patients receiving neoadjuvant radiochemotherapy. PATIENTS AND METHODS: Eighty-five consecutive patients with localized esophageal cancers (cT2-4, Nx, M0) received standardized neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil, 36 Gy). Seventy-four (87%) patients were resected by transthoracic en bloc esophagectomy and 2-field lymphadenectomy. The entire tumor beds of the resected specimens were evaluated histomorphologically, and regression was categorized into grades I to IV based on the percentage of vital residual tumor cells (VRTCs). A major response was achieved when specimens contained either less than 10% VRTCs (grade III) or a pathologic complete remission (grade IV). RESULTS: Complete resections (R0) were performed in 66 of 74 (89%) patients with 3-year survival rates of 54% +/- 7.05% for R0-resected cases and 0% for patients with incomplete resections or tumor progression during neoadjuvant therapy (P < 0.01). Minor histopathologic response was present in 44 (59.5%) and major histopathologic response in 30 (40.5%) tumors. Significantly different 3-year survival rates (38.8% +/- 8.1% for minor versus 70.7 +/- 10.1% for major response) were observed. Univariate survival analysis identified histomorphologic tumor regression (P < 0.004) and lymph node category (P < 0.01) as significant prognostic factors. Pathologic T category (P < 0.08), histologic type (P = 0.15), or grading (P = 0.33) had no significant impact on survival. Cox regression analysis identified dichotomized regression grades (minor and major histomorphologic regression, P < 0.028) and lymph node status (ypN0 and ypN1, P < 0.036) as significant independent prognostic parameters. A 2-parameter regression classification system that includes histomorphologic regression (major versus minor) and nodal status (ypN0 versus ypN1) was established (P < 0.001). CONCLUSIONS: Histomorphologic tumor regression and lymph node status (ypN) were significant prognostic parameters for patients with complete resections (R0) following neoadjuvant radiochemotherapy for esophageal cancer. A regression classification based on 2 parameters could lead to improved objective evaluation of the effectiveness of treatment protocols, accuracy of staging and restaging modalities, and molecular response prediction.

Adenocarcinoma↗