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PubMed2006

Survival and outcomes of pulmonary resection for non-small cell lung cancer in the elderly: a nested case-control study.

BACKGROUND: We assessed the morbidity, mortality, and long-term survival of pulmonary resection for non-small cell lung cancer (NSCLC) in elderly patients in three subgroups: 70 years or greater, 75 years or greater, and 80 years or greater. METHODS: A nested case-control study over a 5-year period using an electronic prospective database (n = 6,450) of patients with NSCLC who underwent complete resection. Patients 70 years or older, 75 years or older, and 80 years or older were matched 1:1 to younger controls for stage, pulmonary function, performance status, and type of pulmonary resection. RESULTS: There were 726 patients: 363 were 70 years of age or older (191 patients were 70 to 74 years old, 121 were 75 to 79, and 51 patients were 80 or older). There were 363 patients younger than 70 years of age. There was no significant difference in length of stay, major morbidity, or operative mortality between any of the elderly groups and the younger controls. However, elderly patients who received neoadjuvant therapy had three times the risk of developing major morbidity (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.14 to 7.41). There was a statistically significant better 5-year survival in elderly patients with stage I NSCLC (78% vs 69%, p = 0.01); however, survival was similar for all other stages. CONCLUSIONS: Elderly patients with NSCLC should not be denied pulmonary resection based on chronologic age. Their short-term risks and long-term survival are similar to younger patients. Additionally, there seems to be no increased risk in selected octogenarians. However, elderly patients had double the risk for developing major morbidity after resection if they underwent neoadjuvant therapy.

Aged↗
PubMed2002

Surgical and oncological advances in the treatment of esophageal cancer.

BACKGROUND: Chemoradiotherapy (CR) and hyperthermochemoradiotherapy (HCR) have been performed on numerous patients with esophageal cancer. These neoadjuvant therapies for esophageal cancer are done widely. The purpose of this study is to demonstrate the recent advances in surgical and oncological treatment. METHODS: From 1967 to 2000, 847 patients who underwent an esophagectomy were classified into 4 groups according to the date of operation. Group 1 consisted of 110 patients who underwent an esophagectomy in the first 10-year period (1967-1976), group 2 consisted of 194 patients who had operations from 1977 to 1986, group 3 comprised 400 patients who had operations from 1987 to 1996, and group 4 comprised 143 patients who had operations from 1997 to 2000. From 1967 to 2000, 322 patients with neoadjuvant therapy and esophagectomy were classified into 6 groups according to the kinds of anticancer drugs that were administered. Group A received regimen A, using BLM (5 mg iv) 6 times as the chemotherapeutic drug in the early period (1965-1990); group B received regimen B, using cis-diaminedichloroplatinum (CDDP) (40 mg/m2) 3 times as the chemotherapeutic drug in the second period (1990-1997); and group C received regimen C, using CDDP (40 mg/m2) and 5FU (250 mg/m2) daily in the most recent period (1997-2000). The HCR group was also divided into the following 3 groups: Group D, who received regimen A and hyperthermia 6 times in the early period; group E, who received regimen B and hyperthermia 6 times in the next period; and group F, who received regimen C and hyperthermia 6 times in the most recent period. The local response and the long-term results were investigated. RESULTS: A complete removal of the primary tumor was achieved in 29%, 39%, 62%, and 68% of the patients in groups 1, 2, 3, and 4, respectively. The 30-day operative mortality rates were 11%, 4%, 1%, and 0% in groups 1, 2, 3, and 4, respectively. The 5-year survival rates for all patients in groups 1, 2, and 3 were 16.7%, 19.2%, and 44.4%, respectively. The cases in which CR or HCR was evaluated to be effective numbered 44 (48.4%) in group A, 22 (73.3%) in group B, 8 (66.7%) in group C, 79 (63.7%) in group D, 36 (73.5%) in group E, and 12 (75.0%) in group F. Our clinical results thus showed CDDP to have a greater effect than BLM, while HCR was shown to have a greater effect than CR. CONCLUSIONS: Preoperative therapy, especially using CDDP and hyperthermia, has improved thanks to recent advances in the treatment of esophageal cancer.

Adult↗
PubMed2003

Pathological features of breast cancer response following neoadjuvant treatment with either letrozole or tamoxifen.

Morphological characteristics, grading features, proliferation marker MIB1, apoptosis (by Tdt-mediated duTP-biotin nick-end labelling (TUNEL)), Bcl-2 expression, oestrogen receptor (ER) and progesterone receptor (PgR) status were compared in ER-positive breast cancers before and after 3 months of neoadjuvant therapy with either letrozole or tamoxifen. Daily treatment was with letrozole 2.5 mg (12 patients) or 10 mg (12 patients), or with tamoxifen 20 mg(24 patients). Letrozole treatment was associated with a pathological response in 17 of 24 (71%) patients. The predominant change in grading features was a decrease in mitosis, and the expression of MIB1 was reduced in all of the 22 evaluable cases. Whilst only marginal changes were observed in ER expression following letrozole therapy, PgR reactivity was reduced in 20 of 21 evaluable cases which were initially PgR-positive, becoming undetectable in 16 patients. Tamoxifen treatment was associated with pathological response in 15 of 24 (63%) tumours. In contrast to letrozole, the dominant change in grading feature was an increase in tubule formation, ER score was markedly reduced in most cases, and the most common effect on PgR was an increased expression. Following treatment with either tamoxifen or letrozole, variable effects were observed on the apoptotic index and expression of Bcl-2. These results indicate that both letrozole and tamoxifen have marked influences on the pathological features of breast cancer during neoadjuvant therapy. However, the effects of the two agents varied such that the phenotypes of letrozole- and tamoxifen-treated tumours differ markedly. Effects on clinical, pathological and biological endpoints were frequently disconcordant--future studies will therefore require the evaluation of multiple parameters in order to fully assess tumour response.

Antineoplastic Agents↗
PubMed2000

[Perioperative morbimortality in pneumonectomy. Analysis of risk factors].

UNLABELLED: Pneumonectomy continues to be associated with high rates of morbidity and mortality. OBJECTIVE: The aim of this study was to determine the mortality and morbidity rates after pneumonectomy and to analyze perioperative risk factors related to mortality. PATIENTS AND METHODS: The cases of 266 patients undergoing pneumonectomy between January 1986 and December 1997 were reviewed retrospectively: 241 patients with lung cancer, 4 with pulmonary metastasis, 9 with bronchiectasis and 12 with other benign diseases; 13% received neoadjuvant therapy. The bronchial stump was stapled in 92%, sutured in 8%, and covered with autologous tissue in 73%. Intrapericardial pneumonectomy was performed in 32%, pneumonectomy extended to the chest wall or diaphragm in 9%, and completion pneumonectomy was performed in 3%. We collected general demographic data, medical histories, pulmonary function data and surgical technique. Deaths and postoperative complications within the first 30 days after pneumonectomy were also known. RESULTS: Two hundred sixty-six pneumonectomies were performed [right 102 (38%); left 164 (62%)] in 249 men (93%) and 17 women (7%) who were 58 +/- 11 years of age (20 to 79 years). The rate of early postoperative death (30 days) was 5.6%. Mortality rates were higher among patients over 70 years of age (p = 0.045), diabetics (p = 0.038), patients undergoing neoadjuvant therapy (p = 0.031), those with FEV1 under 1,800 ml (p = 0.013), cases of right-sided pneumonectomy (p = 0.001), cases of extended pneumonectomy (p = 0.037) or those without coverage of the bronchial stump (p = 0.005). Mortality was also higher when complications appeared involving the bronchial stump (p < 0.01), heart (p < 0.001), respiration (p < 0.001) or digestion (p = 0.002). Overall morbidity was 40%. Surgical complications developed in 23%: postpneumonectomy empyema (10%), bronchopleural fistula (7%) (with no significant difference related to stapling or suturing), hemothorax (3%) and wound complications (3%). Twelve patients (4.5%) underwent second operations. Cardiac morbidity was 20% (atrial fibrillation in 12%), respiratory morbidity was 8% and other complications appeared in 19% of cases. CONCLUSION: In our experience, mortality after pneumonectomy is 5.6% with an overall complication rate of 40%, mainly due to surgical and cardiac complications. Coverage of the bronchial stump with autologous tissue reduces the risk of postoperative death due to fistula and/or empyema after pneumonectomy.

Adult↗
PubMed2005

High-risk localized prostate cancer: a case for early chemotherapy.

High-risk tumors exhibit a more aggressive natural history and have higher positive margin and recurrence rates after radical prostatectomy or radiotherapy alone, where unimodality therapy likely represents undertreatment. Hence, the therapeutic ratio (patients who actually realize a survival benefit from a therapeutic intervention) may, therefore, be greater in high-risk disease if its natural history can be altered by multimodality therapy. It is, thus, important to investigate therapies that optimize complete extirpation of all cancer cells and reduce the incidence of positive surgical margins and disease recurrence. Neoadjuvant therapy extends the logic of early adjuvant therapy further by applying systemic therapy earlier in the course of the disease before definitive locoregional therapy. In prostate cancer, outcomes have not been improved significantly when neoadjuvant hormone therapy is used before surgery; although outcomes are improved when androgen ablation is combined with radiotherapy, many patients remain at risk for systemic recurrence. With recent data confirming improved survival data with docetaxel chemotherapy in metastatic disease, future trials are now focusing on earlier combinations of chemohormonal or biologic therapies in high-risk patients.

Antineoplastic Agents, Hormonal↗
PubMed1992

Effects of preoperative chemotherapy on gastric adenocarcinomas. A morphologic study of 25 cases.

BACKGROUND: Surgical neoadjuvant therapy for gastric adenocarcinoma affords the opportunity to evaluate critically the histologic effects of preoperative chemotherapy. METHODS: Morphologic alterations in gastric adenocarcinomas were examined in the surgical-resection specimens from 25 patients after 6 weeks of preoperative chemotherapy. The group included 1 patient with a complete response; 4, with subtotal responses; 4, with partial responses; and 16, with no response to preoperative chemotherapy. RESULTS: Histologic manifestations of preoperative chemotherapy included mucosal edema, aggregates of histiocytes in the submucosa and muscularis externa, and stromal fibrosis of the submucosa and muscularis externa. Cytologic manifestations were uncommon and included a single case of signet ring cell carcinoma with diminution of the cytoplasmic vacuoles after preoperative chemotherapy. Clinical follow-up was limited, but 3 of the 25 patients died within 5-8 months after the diagnosis of gastric adenocarcinoma. The gastric-resection specimens from these three patients did not show any histologic manifestations of preoperative chemotherapy. CONCLUSION: As in tumors at other sites, the efficacy of surgical neoadjuvant therapy for gastric adenocarcinoma can be assessed, based on the histologic response of the resected tumor to preoperative chemotherapy.

Adenocarcinoma↗
PubMed2001

The role of adjuvant therapy after liver resection for colorectal cancer metastases.

Intrahepatic recurrence is common after major resection for colorectal cancer (CRC) metastases to the liver. In this review, the available data on different adjuvant therapies from systemic chemotherapy to regional approaches by direct perfusion of chemotherapeutic agents via the hepatic artery and portal vein will be discussed. Intraperitoneal administration of chemotherapy is another form of regional therapy. Novel approaches with immunotherapy and trials of neoadjuvant therapy in association with resection of CRC hepatic metastases have also been reported. The purpose of this review is to outline these various strategies and their role in combination with resection of CRC liver metastases. Although improved hepatic disease-free survival has been demonstrated with some strategies, overall survival is minimally affected and recurrence of metastatic disease at distant sites is still a major problem. Therefore, future directions should incorporate the use of new systemic agents effective against CRC metastases. Identification of subgroups through clinical features, molecular markers, proteins, or specific tumor properties may also help to individualize treatment.

Antineoplastic Agents↗
PubMed2001

Transthoracic esophagectomy with radical mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for esophageal carcinoma.

BACKGROUND: Several techniques for esophageal resection have been reported. This study examines the morbidity, mortality, and early survival of patients after transthoracic esophagectomy for esophageal carcinoma using current staging techniques and neoadjuvant therapy. The technique includes right thoracotomy, laparotomy, and cervical esophagogastrostomy (total thoracic esophagectomy) with radical mediastinal and abdominal lymph node dissection. METHODS: Three hundred forty-two patients had surgery for esophageal carcinoma between 1989 and 2000 at our institution. Two hundred fifty consecutive patients had esophagectomy using this technique. Kaplan-Meier curves and univariate and multivariate analyses were performed by postsurgical pathologic stage. RESULTS: Median age was 62.7 years (31 to 86 years). Fifty-nine were female. Eighty-one percent (202) had induction chemotherapy (all patients with clinical T3/4 or N1). Early postoperative complications included recurrent laryngeal nerve injury (14% [35]), chylothorax (9%, [22]), and leak (8%, [19]). Median length of stay was 13 days (5 to 330 days). In-hospital or 30-day mortality was 3.6% (9). Overall survival at 3 years was 44%; median survival was 25 months, and 3-year survival by posttreatment pathologic stage was: stage 0 (complete response) (n = 60), 56%; stage I (n = 32), 65%; stage IIA (n = 67), 41%; stage IIB (n = 30), 46%; and stage III (n = 49), 17%. Mean follow-up was 24 months (SEM 1.6, 0 to 138 months). Five patients with tumor in situ, 6 patients with stage IV disease, and 1 patient who could not be staged (12 pts) were excluded from survival and multivariate calculations. In univariate and different models of multivariate analysis, age more than 65 years, posttreatment T3, and nodal involvement were predictive of poor survival. For univariate analysis, p = 0.002, p = 0.004, p = 0.02, respectively; for multivariate analysis, p = 0.001, p = 0.003, p = 0.02, respectively. CONCLUSIONS: Total thoracic esophagectomy with node dissection for esophageal cancer appears to have acceptable morbidity and mortality with encouraging survival results in the setting of neoadjuvant therapy. Patients who show complete response after induction chemoradiotherapy appear to have improved long-term survival.

Abdomen↗
PubMed1999

Dose-intense salvage therapy after neoadjuvant chemotherapy: feasibility and preliminary results.

Breast cancer patients who, following treatment with primary chemotherapy (FAC 50) present an axillary node involvement of more than 4 nodes together with clinically palpable residual disease (minor response to chemotherapy) and the presence of tumour cell emboli in lymphatics have a very poor outcome. DFS rates of 50 patients treated between 1990 and 1994 were 31% at 5 years. Our aim was therefore to evaluate an entirely different therapeutic regime in these very high risk patients. 32 patients selected for these criteria entered a pilot study consisting in treatment with 3 four weekly cycles of vinorelbine, ifosfamide, cisplatinum followed by a high dose chemotherapy (HDCT) course and rescue by peripheral hematopoietic stem cells which had been collected by cytapheresis after the second course of chemotherapy. HDCT consisted of thiotepa, L-Pam, CBDCA (800 mg/m(2) d1), ifosfamide and mesna. Following primary chemotherapy, 14 patients had breast conservation and 18 had a modified mastectomy. Median number of involved lymph nodes was 11 (range 4-26). 29 patients received the complete HDCT course. Median age was 40 (range 24-59). Engraftment was prompt with a median of 10 days to leucocyte recovery to 1,000/microl and 9 days to platelet recovery. One patient developed reversible renal failure, and subsequently died of Gram-septicemia. To date, with a median follow up of 20 months (range 14-36), 6 patients have relapsed and 2 patients have died. It is too early to make any firm conclusions, but we feel that this alternative regime is feasible and may prove superior to the classical optimal dose anthracycline-containing regimes in patients who have a tendency to rapidly develop resistance to anthracyclines.

Adult↗
PubMed1997

Preliminary results of a phase II study of high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients with anal canal cancer: a French cooperative study.

BACKGROUND: Chemotherapy (5-fluorouracil-mitomycin C) concomitant with radiotherapy (RT) increases local control and colostomy-free survival in advanced anal canal carcinomas (ACC). The purpose of this prospective trial was to analyse the toxicity of and response to an induction chemotherapy combining 5-fluorouracil (5-FU) and CDDP administered concomitantly with irradiation. PATIENTS AND METHODS: Thirty patients (24 F/6 M, mean age 60, range 38-74) with an advanced ACC > 40 mm and/or with node involvement were prospectively treated (1 T1, 16 T2, 8 T3, 5 T4, 10 N1, 1 N2, 8 N3) from November 1994 to January 1996. Two induction and two concomitant cycles of 5-FU (800 mg/ m2 D1-4 infusion) and CDDP (80 mg/i.v./m2 at D1) were delivered. RT consisted of 45 Gy (1.8 Gy/fr, 5 fr/w) on pelvis +/- inguinal nodes or 30 Gy (3 Gy/fr, 4 fr/w) by direct perineal field. A boost (15-20 Gy) was delivered six weeks later. RESULTS TOXICITY: one patient died of a pulmonary embolism on D4. The remaining 29 received the entire treatment, with reduced 5-FU doses in 11 patients because of acute toxicity. The RT boost was delayed for one patient (aplasia). In 109 cycles, 3 grade 4 and 17 grade 3 toxicities were observed; there were no toxic deaths. Tumor response: the complete response (CR) and partial response (PR) rates were, respectively, 11% and 61% after induction chemotherapy, 59% and 31% after concomitant radiochemotherapy and 96% and 0% two months after completion of the treatment. No tumor progression was observed. CONCLUSION: the treatment was well tolerated and there was good compliance. After induction chemotherapy, most of the patients were in PR, with some even in CR. After completion of the treatment all but one were in CR. The tumor response and the long term results of 50 patients will be analysed before initiation of a randomised trial is considered.

Adult↗
PubMedDate not supplied

Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer.

PURPOSE: Currently available treatment modalities for high-risk clinically localized prostate cancer have limited chances of achieving complete tumor elimination because of either inadequate local or metastatic tumor eradication. The goal of this phase I/II study is to evaluate the safety and efficacy of neoadjuvant docetaxel and mitoxantrone before prostatectomy. MATERIALS AND METHODS: A total of 22 men with high-risk clinically localized prostate cancer underwent weekly treatment with docetaxel (35 mg/m(2)), with increasing doses of mitoxantrone (2-5 mg/m(2)) for a 12 of 16-week treatment cycle before prostatectomy. Testosterone and prostate-specific antigen (PSA) measurements were made before and after chemotherapy. RESULTS: The maximally tolerated dose for mitoxantrone was 4 mg/m(2), and the primary toxicity was neutropenia. Testosterone levels were maintained throughout treatment. PSA reductions were observed in 95% of patients, with a median reduction of 41%. The surgery was well tolerated after chemotherapy, without any major complications. Negative surgical margins were attained in 76% of patients. CONCLUSIONS: Administration of multi-agent chemotherapy before prostatectomy was safe in this population. This regimen appeared to have antineoplastic activity as evidenced by PSA reductions in the absence of significant testosterone changes. The benefit of chemotherapy for improving surgical margin rates could not be determined outside of a phase III trial because the effect of patient or surgeon factors could not be dissected from the potential effect of neoadjuvant therapy. Continued study of novel agents in the neoadjuvant setting is warranted because this approach allows for the rapid identification of active agents and for molecular investigation into the mechanism of drug activity.

Aged↗
PubMed1998

Management of primary urethral cancer.

OBJECTIVES: To determine the best therapeutic approach for treatment of patients with urethral cancer according to tumor location and clinical-pathologic stage. METHODS: A retrospective review of 21 consecutive patients diagnosed with primary urethral carcinoma was performed. Clinical-pathologic staging, treatment modality, and outcome were analyzed. RESULTS: The overall survival rate was 62%. In patients with clinical Stage Ta-2N0M0 tumors, 8 of 9 patients (89%) are free of disease compared to 5 of 12 patients (42%) with Stage T3-4N0-2M0 tumors (P = 0.03). Best treatment outcome for patients with Stage T3 disease or higher was obtained when multimodality therapy (neoadjuvant chemotherapy and radiation therapy with or without surgery) was administered, with a disease-free survival rate of 60%. CONCLUSIONS: Clinical-pathologic stage was a strong predictor of disease-free survival rate. For patients with Ta-2N0M0 tumors, multimodality therapy may not be required. Conversely, best treatment outcomes in patients with T3-4N0-2M0 tumors are obtained by administering a multimodal therapy combining chemotherapy and radiation therapy with surgical resection.

Adult↗
PubMedDate not supplied

Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer.

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.

Antineoplastic Agents↗