Preoperative Chemotherapy In Patients Research Articles

Preoperative chemotherapy in patients undergoing resection of colorectal liver metastases: Assessment of pattern of tumor response using CT registration imaging.

252 Background: A significant radiologic response from preoperative chemotherapy may successfully convert some unresectable colorectal liver metastases (CRLM) to resectable disease. Understanding the pattern of tumor shrinkage in relation to the hepatic structures such as the liver capsule and vascular pedicles is important. We sought to determine the spatial relationship between individual liver metastases before and after chemotherapy, as well as to adjacent intrahepatic structures. Methods: Using nonrigid registration of temporally separated CT scans before and after preoperative chemotherapy, 42 CRLM were evaluated in 27 patients with radiologic partial response. The response pattern was determined by independent observers and scored as: (1) asymmetric toward the liver periphery, (2) asymmetric toward the liver center, and (3) symmetric response. In addition, the shrinking pattern was characterized in relation to the liver capsule and major vascular pedicles, as well as clinicopathologic features. Results: Among the tumors evaluated, 38/42 lesions (90%) responded asymmetrically, with only 10% undergoing a symmetric contraction. 43% shrank toward the periphery and 47% centrally. Tumors in proximity to the liver capsule were more likely to respond peripherally compared to deeper lesions (p=0.013). Unexpectedly, R1 resection was more common in tumors with peripherally directed response vs. those with central or symmetric response (p=0.027). In addition, tumors within 5 mm of a single major vascular pedicle were more likely to shrink toward (59%) and not away from the vessel. No difference in response pattern was observed in relation to tumor size, chemotherapy regimen, or presence of steatosis. Conclusions: Tumors were found to respond asymmetrically in the vast majority of cases, either toward or away from the liver center. In addition, tumors in proximity to major vascular pedicles less commonly move away from these structures. These findings may have important implications when planning curative-intent resection or anticipating the ability to convert patients to resectable disease using preoperative chemotherapy. No significant financial relationships to disclose.

Predictive factors of pathologic complete response and clinical tumor progression after preoperative chemotherapy in patients with stage II and III breast cancer

This study aimed to define predictive factors of pathologic complete response (pCR) and disease progression in stage II and III breast cancer patients. Three hundred thirty-eight patients were included in the study. Patients had received preoperative chemotherapy as follows: 101 had doxorubicin plus cyclophosphamide (AC); 91 had doxorubicin plus docetaxel; 103 had docetaxel plus capecitabine; and 43 had paclitaxel plus gemcitabine. A pCR was defined as the absence of residual invasive carcinoma in the breast. The majority of patients (73%) were premenopausal with a median age of 44 (range, 21-76) years. Fifty-four patients (16%) achieved pCR and were distributed among the 4 breast cancer subtypes as follows: 10% of patients with -ER or PR+/HER2-, 13% with ER or PR+/HER2+, 33% with ER-/PR-/HER2+, and 19% with ER-/PR-/HER2-(p = 0.001). Taxane-containing regimen (p = 0.042) and Breast cancer subtype (p = 0.005) were significant predictive variables for pCR. On the other hand, significantly more patients who received non-taxane-containing regimen (AC) experienced no response (p = 0.001) or progression (p = 0.006). Patients with ER-/PR-/HER2+ tumors and those who received taxane-containing regimen achieved a higher pCR rate, while significantly more patients developed tumor progression by preoperative non-taxane-containing regimen (AC) compared to those who received taxane-containing chemotherapy.

The timing of surgery for resectable metachronous liver metastases from colorectal cancer: Better sooner than later? A retrospective analysis

Background The benefit of preoperative chemotherapy in patients with initially resectable liver metastases from colorectal cancer is still a matter of debate. Aims We aim to evaluate the role of neoadjuvant chemotherapy on the outcome of patients with colorectal cancer metachronous liver metastases undergoing potentially curative liver resection. Methods One-hundred four patients were available for analysis. Tested variables included age, sex, primary tumour TNM stage, location and grading, the number of liver metastases, monolobar or bilobar location, interval time between liver metastases diagnosis and liver resection, Fong Clinical Risk Score (CRS). Neoadjuvant chemotherapy was administered according to the FOLFOX4 regimen. Results Forty-four patients underwent liver resection without receiving neoadjuvant chemotherapy (group A); 60 patients received neoadjuvant chemotherapy (group B). At univariate analysis, only the time of liver resection seemed to affect overall survival: patients in group A showed a median survival time significantly superior to that of patients in group B (48 vs. 31 months; p = 0.0358). Conclusions Our findings suggest that, when feasible, resection of liver metastases should be considered as an initial approach in this setting. Further studies are needed to better delineate innovative therapeutic strategies that may lead to an improved outcome for colorectal cancer patients with surgically resectable liver metastases.

Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases.

The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM. A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1-8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared. Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency (P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups. Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.

Histologic changes associated with false‐negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node‐positive breast cancer before treatment

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. 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. 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. 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.

Predictive value of neoadjuvant chemotherapy failure in breast cancer using FDG-PET after the first course.

563 Background: To prospectively evaluate the predictive value of FDG-PET to detect the absence of clinical and pathological response to preoperative chemotherapy in patients (pts) with breast cancer. Methods: 63 consecutive pts with nonmetastatic, noninflammatory advanced breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 docetaxel) were enrolled. Fifty-two were assessable (4 non eligible, 7 non evaluable). Median age of assessed pts was 49 years. There were 63% T2 and 37% T3, with 98% invasive ductal carcinomas. FDG-PET was performed before the first and the second course. Metabolic activity (tumor FDG uptake) was measured by standardized uptake value (SUVmax). Patients were classified as non responders (NR) when the decrease of SUVmax in the primary tumor was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after 3 cycles, pathologic complete response (pCR) after surgery (according to Sataloff classification) and patient disease free survival. Results: Out of the 38 patients with a PET response (SUV decrease more than 15%), 25/38 (66%) had a clinical response after the third cycle and 10/33 (30%) had a pCR. Out of the 14 patients with no PET response, (SUV decrease less than 15%), only 1/14 (7%) had a clinical response after the third cycle and no pCR was observed. The 3-year disease-free survival (DFS) rate was significantly longer for metabolic responders than for non responders (respectively 94±4% vs. 69±13%; p = 0.0008). In this population the pCR, as expected, was also a significant prognostic factor on 3 year- DFS rate (p = 0.02). Conclusions: This prospective study shows that a decrease in the SUV less than 15% after the first chemotherapy course is a very potent predictor of failure to neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this has been shown despite the fact that the chemotherapy regimen was changed after the third course. No significant financial relationships to disclose.

A phase II study evaluating the role of sentinel lymph node surgery and axillary lymph node dissection following preoperative chemotherapy in women with node-positive breast cancer (T1-4, N1-2, M0) at initial diagnosis: ACOSOG Z1071.

TPS118 Background: In patients presenting with lymph node positive breast cancer who undergo preoperative chemotherapy the standard of care is completion axillary lymph node dissection (ALND) at the time of surgical resection. The goal of this phase II single-arm study is to evaluate the false-negative rate (FNR) of sentinel lymph node (SLN) surgery after completion of neoadjuvant chemotherapy in patients who initially presented with node-positive disease. If results of this study show that SLN surgery has an acceptable FNR for staging of the axilla after preoperative chemotherapy in patients who initially had node-positive disease, this would change the surgical standard of care for these patients and patients with negative SLNs could be spared the morbidity of complete ALND, significantly reducing the short-term and long-term surgical morbidity associated with the treatment of node-positive breast cancer. Methods: Single-arm study activated in July 2009 with a target accrual of 550 patients. The primary objective is to determine the false- negative rate (FNR) for SLN surgery. FNR is defined as the number of patients declared to have no evidence of cancer in the SLN and are found to have at least one positive lymph node in the ALND divided by the total number of patients with at least one positive axillary lymph node by ALND. Eligible patients are adult women with biopsy-proven invasive breast cancer and biopsy of an axillary lymph node documenting nodal disease prior to initiation of preoperative chemotherapy. Patients with prior ipsilateral axillary surgery or SLN surgery are not eligible. Imaging correlatives will determine how the axillary ultrasound status of the patient upon completion of preoperative chemotherapy (evidence of residual lymphadenopathy on ultrasound versus no evidence of lymphadenopathy) affects the FNR of SLN surgery and how sonographic findings correlate with residual disease on final pathology. Additional correlative science studies will examine the incidence, risk factors, and changes in quality of life associated with the development of lymphedema following ALND. No significant financial relationships to disclose.

S1879 The Incidence of Hepatic Toxicity Following Preoperative Chemotherapy in Patients Undergoing Hepatic Resections for Colorectal Metastasis

S1879 The Incidence of Hepatic Toxicity Following Preoperative Chemotherapy in Patients Undergoing Hepatic Resections for Colorectal Metastasis

Titration of Serum p53 Antibodies Predicts Pathological Response in Women with Operable Early Stage Breast Cancer Receiving Preoperative Sequential FEC and Docetaxel Chemotherapy.

Abstract Background: In breast cancer, emerging dates demonstrate that p53 mutation is associated with response to preoperative chemotherapy, indicating that p53 mutation may be a predictive factor for response to preoperative chemotherapy. The accumulation of mutant p53 protein has been found to induce the formation of serum p53 IgG antibodies in breast cancer patients. A highly specific quantitative enzyme-linked immunosorbent assay (ELISA) kit has been developed to detect p53 antibody titers. However, whether this titration of serum p53 antibody reflects response to preoperative chemotherapy is unknown. The aim of this study was to evaluate the clinical implication of serum p53 antibody titers as a predictive factor for preoperative chemotherapy in breast cancer.Patinets and Methods: In this study, we analyzed 103 women with operable early stage breast cancer treated by preoperative chemotherapy and definitive curative surgery. Patients received four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 q3w) followed by four cycles of docetaxel (75 mg/m2 q3w). The pretreatment serum samples were used to determine the p53 antibody titers. The test's cut-off value was determined to be 1.3 U/ml based on reference distribution in healthy control individuals.Results: Twenty-three of 103 patients (22.3%) were positive for serum p53 antibody. The frequency of pathological complete response (pCR) was significantly higher in cases with positive for p53 antibody than in patients with negative for p53 antibody (9/23 or 39% vs. 15/80 or 23%; p=0.04). According to intrinsic subtypes, the tendency was most emphasized in cases with HER2-positive cases (6/9 or 67% vs. 8/25 or 32%). Interestingly, among 8 patients with high p53 antibody titers (>100 IU/ml) 7 patients experienced pCR and remaining one patients showed only foci invading areas in primary tumor and complete remission in axillary lymph node metastasis, suggesting that the value of p53 antibody titers may more precisely predict response to preoperative chemotherapy.Conclusion: p53 mutation analysis using titration of serum p53 antibody is useful predictive test for response to preoperative chemotherapy in patients with breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2038.

Phase I study of apoptosis gene modulation with oblimersen within preoperative chemotherapy in patients with primary breast cancer

Expression of the Bcl-2 protein confers resistance to chemotherapy-mediated apoptotic signals in patients with breast cancer. We investigated effects of Bcl-2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide oblimersen in breast tumor biopsies. Oblimersen targets Bcl-2 messenger RNA (mRNA), down-regulates Bcl-2 protein translation and enhances antitumor effects of subtherapeutic chemotherapy doses. Within a phase I trial, we administered escalating doses of oblimersen (3, 5 or 7 mg/kg/day) as continuous infusion on days 1–7 in combination with standard-dose docetaxel (Taxotere), Adriamycin and cyclophosphamide (TAC) on day 5 as preoperative chemotherapy in 28 patients with T2–4 tumors. Effects of oblimersen were evaluated in tumor biopsies and peripheral blood mononuclear cells (PBMCs) 4 days after start of oblimersen and before TAC treatment by quantitative microfluidic real-time PCR. Read-outs consisted in measurement of Bcl-2 mRNA modulations and of 18 putative predictive markers. Two of 13 patients showed a diminution of Bcl-2 transcripts after 4 days of treatment with oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a surrogate tissue because no qualified RNA could be isolated. Nevertheless, we demonstrated feasibility to process clinical samples and to obtain good quality RNA from tumor biopsies and indicated the potential of oblimersen to lower Bcl-2 mRNA in breast cancer.

Long-Term Results of a Randomized Trial of Surgery With or Without Preoperative Chemotherapy in Esophageal Cancer

OEO2 is a randomized, controlled trial of preoperative chemotherapy in patients undergoing radical surgery for esophageal cancer. Random assignment was to surgery alone (S) or to two cycles of combination cisplatin and fluorouracil before surgery (CS). Initial results reported in 2002 demonstrated an advantage for both disease-free and overall survival in the CS group. The analysis has now been updated after a median follow-up of 6 years. OEO2 recruited 802 patients, 400 on CS and 402 on S. The nature of the first recurrence event and cause of death are detailed. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test. Survival by extent of resection is presented. There were 655 deaths, 335 for S and 320 for CS. The survival benefit has been maintained with a hazard ratio (HR) of 0.84 (95% CI, 0.72 to 0.98; P = .03) which in absolute terms is a 5-year survival of 23.0% for CS compared with 17.1% for S. The treatment effect is consistent in both adenocarcinoma and squamous cell carcinoma. The first disease-free survival event was macroscopic residual disease from incomplete resection (R2) or no resection in 26.4% of the S group versus 14.3% of the CS P < .001. Three-year survival by type of resection was R0 42.4%, R1 was 18.0%, and R2 was 8.6%. Long-term follow-up confirms that preoperative chemotherapy improves survival in operable esophageal cancer and should be considered as a standard of care.

Preoperative chemotherapy for patients with Wilms tumor in Malawi is feasible and efficacious

Wilms tumor has a survival rate of 85-90% in well resourced countries but in low income countries survival is lower. Malawi is a country with very limited resources. We studied the feasibility, toxicity and efficacy of preoperative chemotherapy for Wilms tumor in Malawian children. All patients diagnosed with a Wilms tumor, admitted in Blantyre, Malawi, from 2006 to 2008, were included. These patients received SIOP-based preoperative chemotherapy followed by surgery and risk-stratified post-operative chemotherapy. Social support and counseling were provided to prevent abandonment of treatment. Twenty patients were included. Mean tumor volume at diagnosis was 2,500 ml and eight patients (40%) had metastases. Ninety-five percent of patients presented with hypertension, 80% with microscopic hematuria and 60% with a raised platelet count. Preoperative chemotherapy resulted in >50% tumor reduction in 55% of patients with localized disease and 75% of patients with metastatic disease. During preoperative chemotherapy, 11 of 18 patients experienced >or= grade 3 anaemia, 7 patients experienced >or= grade 3 neutropenia. In 12 patients the tumor was resected. Reasons of treatment failure were: abandonment of treatment (N = 3), death during anaesthesia induction (N = 1), inoperability (N = 5, due to metastatic disease in N = 4) and relapse (N = 2). One patient died of malaria 2 months after completion of chemotherapy. Eight patients (40%) are alive with a median follow up of 8 months (range 0-1.5 years). Preoperative chemotherapy for Wilms tumor is feasible, tolerated and efficacious in Malawi. Continued efforts are needed to encourage early presentation and to prevent abandonment.

P2.92. Efficacy of the S-1/cisplatin preoperative chemotherapy for patients with oral carcinoma

P2.92. Efficacy of the S-1/cisplatin preoperative chemotherapy for patients with oral carcinoma

The Role of Preoperative Chemotherapy in Patients with Resectable Colorectal Liver Metastases

Liver metastases develop in 40-50% of patients with colorectal cancer and represent the major cause of death in this disease. Surgical resection remains the only treatment procedure that can ensure long-term survival and provide cure when liver metastases can be totally resected with clear margins, when the primary cancer is controlled, and when there is no nonresectable extrahepatic disease. Five-year survival rate after surgical resection of colorectal metastases varies from 25% to 55%, but cancer relapse is observed in most patients. To review the potential benefits and disadvantages of neoadjuvant chemotherapy administered before surgery to patients with initially resectable metastases. European Organization for Research and Treatment of Cancer (EORTC) study 40983 has shown that neoadjuvant chemotherapy could reduce the risk of relapse by one-quarter, and allows to test the chemosensitivity of the cancer, to help to determine the appropriateness of further treatments, and to observe progressive disease, which contraindicates immediate surgery. Neoadjuvant chemotherapy can induce damage to the remnant liver. Oxaliplatin-based combination regimen is associated with increased risk of vascular lesions, whereas irinotecan-containing regimens have been associated with increased risks of steatosis and steatohepatitis. Analysis of EORTC study 40983 showed that administration of six cycles of neoadjuvant systemic chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was associated with moderate increase of the risk of reversible complications after surgery, but mortality rate was below 1% and not increased. If patients are not overtreated, chemotherapy before surgery is well tolerated. The integration of novel targeted agents in combination with cytotoxic drugs is a promising way to improve outcome in patients with advanced colorectal cancer. Preliminary trials have shown that targeted agents combined with cytotoxic regimens can increase tumor response rates. Another impact of preoperative chemotherapy is that metastases that respond to treatment may no longer be visible on computed tomography (CT) scan or at surgery. Patients should be carefully monitored and receive surgery before metastases disappear. Treatment of most patients with liver metastases-those with resectable metastases as well as those with initially unresectable metastases-should start with chemotherapy. If drugs are well chosen and the duration of treatment is monitored with care during multidisciplinary meetings, benefits largely outweigh potential disadvantages.

The Case for Selective Use of Pre-Operative Chemotherapy for Hepatic Colorectal Metastases: More Is Not Always Better

The Case for Selective Use of Pre-Operative Chemotherapy for Hepatic Colorectal Metastases: More Is Not Always Better

Phase I study of apoptosis gene modulation with oblimersen within preoperative chemotherapy in patients with primary breast cancer

e11576 Background: The expression of the Bcl-2 protein confers resistance to chemotherapy mediated apoptotic signals in patients with breast cancer. The development of chemo sensitizing drugs may result in new treatment options. We investigated the effects of Bcl-2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide oblimersen in breast tumor biopsies. Oblimersen targets Bcl-2 mRNA, thereby down regulates Bcl-2 protein translation, and enhances the antitumor effects of sub therapeutic doses of docetaxel. Methods: Within a phase I trial we administered escalating doses of oblimersen (3/5/7mg/kg/day) as continuous infusion on day 1–7 in combination with standard dosed docetaxel, doxorubicin, cyclophosphamide (TAC) on day 5 as preoperative chemotherapy in 28 patients with T2–4 breast cancers. Effects of oblimersen were evaluated in tumor biopsies and peripheral blood mononuclear cells (PBMCs) 4 days after start of oblimersen continuous infusion and before TAC treatment by quantitative microfluidic real-time polymerase chain reaction (RT-PCR). Read-outs consisted in measurement of Bcl-2 mRNA modulations and of 18 other putative predictive markers. Results: Two out of 13 patients showed a diminution of Bcl-2 transcripts after 4 days of treatment with oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a surrogate tissue, because no qualified RNA could be isolated. Conclusions: Nevertheless, we demonstrated the feasibility to process clinical samples and to obtain good quality RNA from tumor biopsies, and indicated the potential of oblimersen to lower Bcl-2 mRNA in breast cancer. No significant financial relationships to disclose.

Direct comparison of logistic regression and recursive partitioning to predict chemotherapy response of breast cancer based on clinical pathological variables

The purpose was to compare logistic regression model (LRM) and recursive partitioning (RP) to predict pathologic complete response to preoperative chemotherapy in patients with breast cancer. The two models were built in a same training set of 496 patients and validated in a same validation set of 337 patients. Model performance was quantified with respect to discrimination (evaluated by the areas under the receiver operating characteristics curves (AUC)) and calibration. In the training set, AUC were similar for LRM and RP models (0.77 (95% confidence interval, 0.74-0.80) and 0.75 (95% CI, 0.74-0.79), respectively) while LRM outperformed RP in the validation set (0.78 (95% CI, 0.74-0.82) versus 0.64 (95% CI, 0.60-0.67). LRM model also outperformed RP model in term of calibration. In these real datasets, LRM model outperformed RP model. It is therefore more suitable for clinical use.

Validation of radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas: Japanese Orthopaedic Association Committee on Musculoskeletal Tumors Cooperative Study

BackgroundThe radiographic evaluation of the response to preoperative chemotherapy for bone and soft tissue sarcomas is based mostly on the change in primary tumor size before and after chemotherapy, as is done for many solid cancers. Its prognostic correlation, however, has hardly been validated. MethodsWe conducted a retrospective validation study of the Japanese Orthopaedic Association (JOA) radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas as a JOA Committee on Musculoskeletal Tumors cooperative study. A total of 125 consecutive patients with high-grade bone (n = 77) and soft tissue (n = 48) sarcomas treated with neoadjuvant chemotherapy and definitive surgery in 25 tertiary referral hospitals were selected for the study. We investigated the correlation between the tumor size-based radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas provided by the JOA Committee on Musculoskeletal Tumors (hereafter called the JOA criteria) and the patients’ overall survival using the Kaplan-Meier method and the log-rank test. ResultsThe JOA criteria correlated relatively well with survival for malignant bone tumors (mostly comprising osteosarcoma and Ewing’s sarcoma) but not for soft tissue sarcomas, suggesting that the tumor size-based radiographic evaluation criteria for the response to preoperative chemotherapy in patients with soft tissue sarcomas is invalid. ConclusionsThe JOA criteria, based on the change in primary tumor size, is valid for malignant bone tumors but invalid for soft tissue sarcomas. Other new evaluation modalities of the response to preoperative chemotherapy using innovative functional imaging techniques are needed for soft tissue sarcomas.

Preoperative induction chemotherapy for resectable stage IIIA non-small-cell lung cancer: a meta-analysis of 13 double-blind, randomized clinical trials.

The role of Preoperative chemotherapy in patients with resected nonsmall-cell lung cancer (NSCLC) remains unclear, this study is aimed at evaluating the effectiveness of Preoperative chemotherapy in patients with resected non-small-cell lung cancer (NSCLC), by performing a meta-analysis of relevant trials. Searching the literature from MEDLINE, pubmed, OVID, The Cochrane library, Cancerlit, Clinicaltrials.gov, ASCO, ESMO and CBM database, a meta-analysis was carried out to compare patients with NSCLC receiving chemotherapy before surgery with those undergoing surgery alone. The odds ratio (OR) was estimated to assess the survival advantage of Preoperative chemotherapy. Thirteen eligible randomized controlled trials (RCT) were identified, including 2561 patients, the meta-analysis showed preoperative chemotherapy improved survival with a OR of 0.80 (95% confidence interval, 0.68-0.94; P =0.008) in a subset analysis patients with IIIa stage also benefit from the preoperative chemotherapy. There was no evidence of statistical heterogeneity. This analysis shows a significant benefit of preoperative chemotherapy and is currently the best estimate of the effectiveness of this therapy.

HMGA2 expression and response to anthracycline-based preoperative chemotherapy in patients with operable breast cancer

22035 Background: Preclinical data suggest that increased expression of high mobility group A2 (HMGA2) protein could enhance chemosensitivity towards doxorubicin in breast cancer cells. The present study investigated the predictive value of HMGA2 immunoreactivity in patients (pts) with operable breast cancer (BC) treated preoperatively with regimens including anthracyclines. Methods: We reviewed the pretreatment biopsies of 94 pts with large (> 2 cm) operable BC treated with preoperative anthracycline-based chemotherapy, performing immunohistochemistry for HMGA2 and other biological markers (ER, PgR, HER2, MIB1, topoisomerase II α). Characteristics of preoperative chemotherapy (i.e. number of courses, type of anthracycline or taxane) were also analyzed. Association between clinico-biological factors and pathological, clinical (by caliper) and radiological (by mammography, ultrasound and MRI) response was assessed. Results: In univariate analysis, high expression of HMGA2 was significantly associated with clinical complete response [odds ratio (OR) = 4.9, 95% CI 1.3–18.9] and with tumor shrinkage assessed by MRI (OR = 2.9, 95% CI 1.1–7.7). No statistically significant association was observed between HMGA2 and clinical or pathological response in multivariate analysis. Among the other variables, the following were associated with complete pathological response (pCR): ER (p = 0.005), MIB-1 (p = 0.01) and topoisomerase II alfa (p = 0.05). In multivariate analysis, ER was the only independent predictor of pCR (OR = 0.2, 95% CI 0.03–0.9). The number of chemotherapeutic courses was independently associated with tumor shrinkage assessed by caliper (OR = 9.9, 95% CI 2.4–40.5) and by mammography (OR = 4.02, 95% CI 1.4–11.3). MIB-1 expression was independently associated with tumor shrinkage assessed by ultrasound (OR = 3.8, 95% CI 1.1–13.4) and by MRI (OR = 3.6, 95% CI 1.2–11.3). Conclusions: Immunohistochemical evaluation ofHMGA2 significantly predicted clinical complete response and tumor shrinkage assessed by MRI in patients treated with preoperative anthracycline-based chemotherapy. Although no independent association with response was observed, the potential predictive role of this protein deserves further evaluation. No significant financial relationships to disclose.