Neoadjuvant moderately high-dose chemotherapy with rh-G-CSF in locally advanced breast carcinoma.

The poor results of local treatment for locally advanced breast carcinoma (LABC) justify the use of chemotherapy as primary treatment. Retrospective studies have shown a positive correlation between dose and response rate in advanced breast cancer. G-CSF has shown efficacy in achieving optimal dose intensity and ameliorating chemotherapy-induced myelosuppression. The aim of the present study was to assess the efficacy of a moderately high-dose chemotherapy regimen in terms of response rate, disease-free and overall survival and to assess the role of G-CSF in induced neutropenia. METHODS: Inclusion criteria were the following: age <65 years, WHO performance status <2, histologically proven breast carcinoma, adequate hematologic, renal and hepatic function, stage IIIA or IIIB disease, and no metastatic disease. No prior chemotherapy or radiotherapy was allowed. Three cycles of the following chemotherapy were used preoperatively: epirubicin (100 mg/m2 on day 1), cyclophosphamide (400 mg/m2 for 3 consecutive days) and rh-G-CSF (5 microg/kg/die from day 4 to day 12 every 14 days). After mastectomy or quadrantectomy plus radiotherapy, all patients were treated with 4 courses of adjuvant chemotherapy according to the CMF 1-8 schedule (methotrexate, 40 mg/m2 cyclophosphamide, 600 mg/m2; fluorouracil, 600 mg/m2; all on days 1 and 8, with recycle every 4 weeks). RESULTS: From May 1992 to June 1996, 57 patients with histologically proven LABC were preoperatively treated. Forty-four patients were premenopausal and 13 postmenopausal; the median age was 45 years (range, 29-64). Thirty-five patients had stage IIIA and 22 patients stage IIIB disease (7 with inflammatory disease). Forty-seven patients underwent radical mastectomy and 10 conservative surgery. A clinical response was noted in 93% (95% confidence interval, 83-98%) of patients (12% complete responses and 81% partial responses); 2 pathological complete remissions (3.5%) were obtained. No toxic deaths were observed. All patients had a follow-up of at least 42 months. The overall 5-year survival rate was 76% (standard error--SE), 6%) and the 5-year disease-free survival rate was 68% (SE, 6.3%). CONCLUSIONS: The 14-day regimen was well tolerated and effective in LABC patients, although not superior to standard-dose chemotherapy. To improve results the use of new drugs in controlled clinical trials seems warranted.     

低位直肠癌术前加速放疗的临床意义

Objective To observe the clinical pathological changes lower rectal carcinoma after preoperative radiation.Methods Thirty cases of rectal carcinoma underwent preoperative radiotherapy at a dose of 30 Gy.Gross size of the tumors was measured and histological changes were analyzed before and after radiation.Results The rates of complete regression,partial regression and no response to radiation of the tumors were 23.3%.53.3%and 23.3%.Significant tumor regression RCRG Ⅲ wag seen in 6 cages (20.0%) after radiotherapy.while partially tumor regression RCRG Ⅱ was seen in 15 cases (50.0%). Conclusion Preoperative radiation at a dose of 30 Gy on lower rectal carcinoma induces degeneration and necrosis of the tumor cells with complete or partial regression in most cases.Necrosis,fibrosis and thickening of vascular intima in the rectal cancer tissue after radiotherapy is more frequent than those without radiotherapy.It may be the potential reason for increased resection rate and sphincter saving after radiotherapy. It hag a great significance for sphincter-preservation surgery in this group of rectal carcinomas.     

低位直肠癌术前加速放疗的临床意义

 目的　观察低位直肠癌术前放疗的临床病理变化及意义。方法　对30例已行术前30 Gy（3 Gy／次,2次／d,前后野交替,间隔6 h）生物效应等同于常规放疗40 Gy的低位直肠癌患者进行术后病理变化分析;直肠镜观察放疗前后直肠肿块的肉眼变化、放疗后手术标本的病理形态学特征。结果　放疗后直肠镜仅见小的病灶、肿块缩小和无明显变化者分别为7例（23.3 %）、16例（53.3 %）和7例（23.3 %）。放疗患者按直肠癌组织学退变的分级标准（RCRG）分为Ⅰ级8例（26.7 %）、Ⅱ级15例（50.0 %）、Ⅲ级6例（20.0 %）。结论　术前30 Gy加速放疗可使大多数直肠癌瘤体缩小,使癌组织坏死,癌组织和间质产生纤维变性,降低肿瘤分期,有利于肿瘤的切除;对低位直肠癌保肛手术具有积极的作用。     

低位直肠癌术前加速放疗的临床意义

Objective To observe the clinical pathological changes lower rectal carcinoma after preoperative radiation.Methods Thirty cases of rectal carcinoma underwent preoperative radiotherapy at a dose of 30 Gy.Gross size of the tumors was measured and histological changes were analyzed before and after radiation.Results The rates of complete regression,partial regression and no response to radiation of the tumors were 23.3%.53.3%and 23.3%.Significant tumor regression RCRG Ⅲ wag seen in 6 cages (20.0%) after radiotherapy.while partially tumor regression RCRG Ⅱ was seen in 15 cases (50.0%). Conclusion Preoperative radiation at a dose of 30 Gy on lower rectal carcinoma induces degeneration and necrosis of the tumor cells with complete or partial regression in most cases.Necrosis,fibrosis and thickening of vascular intima in the rectal cancer tissue after radiotherapy is more frequent than those without radiotherapy.It may be the potential reason for increased resection rate and sphincter saving after radiotherapy. It hag a great significance for sphincter-preservation surgery in this group of rectal carcinomas.     

Long-term results of hyperfractionated radiation and high-dose intraarterial cisplatin for unresectable oropharyngeal carcinoma

BACKGROUND: In this report, the authors present the results from a study of patients with unresectable oropharyngeal squamous cell carcinomas who were treated on a protocol of hyperfractionated radiation and high-dose intraarterial cisplatin (HYPERRADPLAT) at the University of Kentucky. METHODS: The study was designed as a prospective, single-armed case series that was conducted in the setting of a single, academic, tertiary referral center. The patient cohort consisted of 24 previously untreated patients who were diagnosed with unresectable oropharyngeal carcinoma and were treated on the HYPERRADPLAT regimen, which included hyperfractionated external beam radiotherapy (1.2 grays [Gy] twice daily) was given for 5 weeks (60 Gy) followed by high-dose intraarterial cisplatin (150 mg/m2) and sodium thiosulfate. Shrinking "large-field" portals were started on Week 6 and finished on Week 7 with a cumulative dose of 76.8-81.6 Gy. The main outcome measures of the study were the primary and neck response rates, the 2-year and 5-year overall survival and disease-specific survival rates, and acute and late treatment morbidity. RESULTS: The median follow-up was 77 months. Complete response rates at the primary and regional lymph nodes were both 88%. The 2-year overall survival and disease-specific survival rates were 57% and 68%, respectively; whereas the 5-year overall survival and disease-specific survival rates were 33% and 42%, respectively. Two patients had Grade 4 mucosal toxicity, and no patient experienced neurologic or significant hematologic toxicities. Within 1 year of treatment, 58% of patients had used a feeding tube. CONCLUSIONS: The HYPERRADPLAT regimen produced excellent response rates and overall survival rates comparable to those achieved by patients who had unresectable oropharyngeal carcinomas. Tolerance of the therapy was good, and further studies using HYPERRADPLAT with induction therapy may improve outcomes further in this subset of patients with unfavorable disease.     

Prognostic significance of circumferential margin involvement in rectal adenocarcinoma treated with preoperative chemoradiotherapy and low anterior resection

INTRODUCTION: Histologic examination of circumferential margins is an important predictor of local and distant relapse in non-radiated rectal cancer. However, for patients who received preoperative chemoradiotherapy this role has not yet been addressed. METHODS: From January 1995 to December 1997, 61 patients with rectal adenocarcinoma located between 0 and 10 cm from anal verge with invasion into perirectal fat assessed by rectal ultrasound were included. All patients received 45 Gy + bolus infusion of 5-FU (450 mg/m(2)/days 1-5, 28-33 of RT); 4-6 weeks later, surgery was performed. Circumferential margin was assessed (<2 mm was considered as positive). Five-year survival was calculated by Kaplan-Meier method and comparison of groups with log-rank test. Multivariate Cox regression analysis was performed to find risk factors affecting local control and survival. RESULTS: There were 35 males and 26 females, mean age 60.3 years. Twelve patients (19.7%) had circumferential margin involvement. Median follow-up was 44 months. Overall local recurrence was observed in 6 of 61 patients (9.8%); in patients without circumferential margin involvement this was 8%, whereas it was 16% in those with circumferential margin involvement (P = 0.33). Distant recurrence was observed in 22% of patients without circumferential margin involvement; conversely, it was 58.3% in those with involvement (P = 0.02). Five-year survival of patients without circumferential resection involvement margin was 81%, while it was 42% in patients with circumferential involvement (P = 0.006). CONCLUSIONS: In patients with rectal cancer treated by preoperative chemoradiation plus total mesorectal excision (TME) and sphincter saving surgery, circumferential margin involvement is associated with high incidence of distant recurrence and cancer-related death.     

Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies

Over the past 5 years, 129 patients have been treated with a combination of high-dose cisplatin (CDDP) and radiation for locally advanced epithelial malignancies. The CDDP was administered at a dose of 100 mg/m2 by iv infusion over one-half hour, no more than 1 hour before irradiation, every 3 weeks during a full course of external beam irradiation. An attempt was made to take advantage of the interaction of high-dose CDDP and radiation. Tumor systems studied included head and neck, ovary, lung, cervix, and prostate. Median survival times are as follows: squamous cell carcinoma of the head and neck (trial 1), 36 months; ovarian carcinoma, 19; and squamous cell carcinoma of the lung, 14. Median survival has not yet been reached in trials of squamous cell carcinoma of the head and neck (trial 2), cervical carcinoma, or adenocarcinoma of the prostate.     

Experience with high-dose radiation therapy and the intestinal sling procedure in patients with rectal carcinoma.

BACKGROUND. Surgery for Dukes' Stage B2 or C rectal carcinoma has a locoregional recurrence rate of 15-67%; this rate is significantly reduced when postoperative radiation therapy (RT) is given. However, RT contributes to radiation-associated small bowel injury in a dose-dependent manner. METHODS. Polyglycolic acid mesh used as an intestinal sling is able to keep the small bowel out of the pelvis during RT, thereby preventing radiation-associated small bowel injury. RESULTS. The authors reviewed the perioperative experiences and acute toxic effects of RT in 53 patients in whom the polyglycolic sling was placed from May 1985 through May 1990 during laparotomy for rectal malignancies (47 primary and 6 recurrent). There were 26 men and 27 women whose ages ranged from 34 to 88 years (mean, 64.7 years). Mild postoperative ileus occurred in most patients, and one patient had an anastomotic leak with a pelvic abscess. Bowel displacement from RT portals was confirmed using radiologic contrast studies. Forty-three patients with primary tumors have completed postoperative RT, and a mean of 5174 cGy has been administered. CONCLUSIONS. After 1-6 years of follow-up (mean, 2.1 years), eight patients have died of systemic disease. There were no cases of radiation-associated small bowel injury and only two cases of pelvic recurrence from primary rectal adenocarcinoma (5%).     

Long-term prognosis after resection of hepatocellular carcinoma associated with hepatitis B-related cirrhosis.

PURPOSE: The optimum management of hepatocellular carcinoma (HCC) associated with cirrhosis has not yet been clarified. Very few data are available in the literature regarding the prognosis after resection of HCC associated with hepatitis B virus (HBV)-related cirrhosis. This study evaluated the long-term results and prognostic factors after resection of HCC complicating HBV-related cirrhosis. PATIENTS AND METHODS: One hundred forty-six patients with HBV-related Child's A or B cirrhosis who had undergone resection of HCC over a 10-year period were prospectively studied for long-term results. They were compared with 155 noncirrhotic patients with HBV-related HCC resected in the same period. RESULTS: The overall survival results of cirrhotic patients after resection of HCC were comparable to those of noncirrhotic patients (5-year survival, 44.3% v 45.6%, respectively; P =.216), but the former group had significantly smaller tumors. Stratified according to tumor size, the survival results were similar between cirrhotic and noncirrhotic patients with tumors 相似文献   

术前放疗加手术与单纯手术治疗喉癌疗效比较的系统评价

目的:比较术前放疗加手术与单纯手术治疗喉癌的疗效,为喉癌治疗方式的选择提供可靠的循证依据.方法:采用系统评价的方法,检索Cochrane中心临床对照试验注册数据库、Medline (OVID)、Embase、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)以及中文科技期刊全文数据库(VIP),截至2009-11-30,以喉癌患者为研究对象,高质量随机对照研究术前放疗加手术与单纯手术的疗效.结果:共纳入6个随机对照试验,研究对象1 127例.术前放疗加手术与单纯手术相比并未提高喉癌患者的3和5年生存率,RR分别为0.94(95%CI为0.72～1.23)和1.09(95%CI为0.87～1.37).术前放疗加手术与单纯手术相比治疗声门上型、声门型以及Ⅱ和Ⅲ期喉癌5年生存率,差异均无统计学意义,RR分别为1.02(95%CI为0.79～1.31)、1.01(95%CI为0.61～1.68)、1.10(95%CI为0.65～1.85)和0.85(95%CI为0.37～1.93).纳入研究均未比较2种治疗后的生存质量.结论:本系统评价纳入研究有限,且无比较2种治疗后生存质量的研究,尚不能得出在喉癌的治疗中术前放疗加手术优于单纯手术治疗疗效的结论.需开展更多高质量研究,对术前放疗加手术与单纯手术治疗喉癌的全面疗效评估提供更可靠的证据.     

Long-term results with oral fluoropyrimidines and oxaliplatin-based preoperative chemoradiotherapy in patients with resectable rectal cancer. A single-institution experience

Introduction

Neoadjuvant 5-FU-based chemoradiotherapy in resectable rectal cancer (RC) is a standard of treatment. The use of oral fluoropyrimidines and new agents such as oxaliplatin may improve efficacy and tolerance.

Material and methods

Between 1999 and 2009, 126 RC patients with T3?CT4 and/or N+ disease were given three successive protocols: UFT (32), UFT-oxaliplatin (75) and capecitabine-oxaliplatin (19), alongside 45 Gy of radiotherapy; with surgery 4?C6 weeks after. Adjuvant treatment was given in all patients. The primary objective was pathologic complete response (pCR).

Results

Preoperative therapy was well tolerated, with no toxic deaths and a 15% grade 3?C4 toxicity rate. Eighty-five percent of patients received the full chemotherapy dose, 56% had an abdominoperineal resection, 6% reinterventions and 57% received the full adjuvant chemotherapy planned. The pCR rate was 13%. The downstaging rate was 80%; 8% had progression of disease. The relapse rate was 20%, with local relapse in 6%. By 5 years of followup, 92% of relapses had occurred. Median follow-up was 73 months, 5- and 10-year disease-free survival rates were 75% and 50%, and 5- and 10-year overall survival rates were 79% and 66% respectively. There was no benefit from the use of oxaliplatin regarding survival or pCR rates. Older patients had worse long-term outcomes.

Conclusions

Neoadjuvant chemoradiotherapy with oral fluoropyrimidines and oxaliplatin is feasible and well tolerated. The risk of early progression is low. However, there was no added benefit with the use of oxaliplatin. There were no relapses in patients with pCR. The role of adjuvant chemotherapy is unclear.     

Laparoscopic anterior resection for rectal carcinoma. Results of a registry.

At the present time, laparoscopic anterior resection of the rectum cannot be recommended for routine use. Such operations should be performed for curative intent only within scientifically valid studies. Furthermore, only interventions involving the upper part of the rectum or the rectosigmoidal junction can, on the basis of the morbidity rate, be justified. Procedures done on the low rectum necessitating a total mesorectal excision technically are difficult and, in the present study, are associated with a significant increase in morbidity, in particular anastomotic leakage. Therefore, tumors in the lower two thirds of the rectum that may be eligible for restorative proctectomy should not be treated for curative intent by the laparoscopic approach. General reservations also persist with regard to compliance with the principles of oncologic radicality.     

Comparison of abdominoperineal resection and low anterior resection in lower and middle rectal cancer

IntroductionThis study aimed to investigate local control and survival rates following abdominoperineal resection (APR) compared with low anterior resection (LAR) in lower and middle rectal cancer.MethodsIn this retrospective study, 153 patients with newly histologically proven rectal adenocarcinoma located at low and middle third that were treated between 2004 and 2010 at a tertiary hospital. The tumors were pathologically staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. Surgery was applied for 138 (90%) of the patients, of which 96 (70%) underwent LAR and 42 were (30%) treated with APR. Total mesorectal excision was performed for all patients. In addition, 125 patients (82%) received concurrent (neoadjuvant, adjuvant or palliative) pelvic chemoradiation, and 134 patients (88%) received neoadjuvant, adjuvant or concurrent chemotherapy. Patients’ follow-up ranged from 4 to 156 (median 37) months.ResultsOf 153 patients, 89 were men and 64 were women with a median age of 57 years. One patient (0.7%) was stage 0, 15 (9.8%) stage I, 63 (41.2%) stage II, 51 (33.3%) stage III and 23 (15%) stage IV. There was a significant difference between LAR and APR in terms of tumor distance from anal verge, disease stage and combined modality therapy used. However, there was no significant difference regarding 5-year local control, disease free and overall survival rates between LAR and APR.ConclusionLAR can provide comparable local control, disease free and overall survival rates compared with APR in eligible patients with lower and middle rectal cancer.     

Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma

The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors' previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals. It is concluded that radionuclide studies of brain, liver-spleen, and bone can be eliminated and can be replaced by CAT scan of brain, chest, and abdomen. Site of recurrence indicate that most intrathoracic recurrences took place outside the radiation therapy field and in the pleural space. An incidental finding was the high incidence of intramedullary spinal cord recurrence.     

Combined preoperative chemotherapy and radiation for locally advanced rectal carcinoma

To determine the efficacy of combined preoperative chemotherapy and radiation therapy for locally advanced rectal carcinoma and the rate of sphincter conservation, a retrospective survey of 39 patients with locally advanced rectal carcinoma treated with various 5-fluorouracil- and leukovorin-based chemotherapy regimens and radiation prior to surgery in a single institution was reviewed. Toxicity, local control and survival were evaluated and compared to previous studies with similarly staged patients. Long-term follow-up was available on 35 patients. The actuarial local failure was 5.7% while the actuarial 5-year survival was 87%. The mortality rate was low (2.5%) and the rate of long-term serious complications acceptable (11.4%). Combined preoperative chemotherapy and radiation provided excellent local regional control despite the poor prognostic factors associated with size, fixation, and the initial advanced tumor stage with acceptable morbidity. In addition, patients with tumors located in the lower third of the rectum may be able to undergo sphincter-sparing surgery. Although the median follow-up is relatively short (32.4 months), the results are in accordance with previous studies of neoadjuvant combined chemotherapy and radiation for locally advanced rectal carcinoma in terms of local and distant control.     

Radical surgical resection and high-dose intraoperative radiation therapy (HDR-IORT) in patients with recurrent gynecologic cancers

OBJECTIVE: To determine the outcome for patients with recurrent gynecologic tumors treated with radical resection and combined high-dose intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between November 1993 and June 1998, 17 patients with recurrent gynecologic malignancies underwent radical surgical resection and high-dose-rate brachytherapy. The mean age of the study group was 49 years (range 28-72 years). The site of the primary tumor was the cervix in 9 (53%) patients, the uterus in 7 (41%) patients, and the vagina in 1 (6%) patient. The treatment for the primary disease was surgery with or without adjuvant radiation in 14 (82%) patients and definitive radiation in 3 (18%) patients. The current surgery consisted of exenterative surgery in 10 (59%) patients and tumor resection in 7 (41%) patients. Complete gross resection was achieved in 13 (76%) patients. The mean HDR-IORT dose was 14 Gy (range 12-15). Additional radiation in the form of permanent Iodine-125 implant was given to 3 of 4 patients with gross residual disease. The median peripheral dose was 140 Gy. RESULTS: With a median follow-up of 20 months (range 3-65 months), the 3-year actuarial local control (LC) rate was 67%. In patients with complete gross resection, the 3-year LC rate was 83%, compared to 25% in patients with gross residual disease, p < 0.01. The 3-year distant metastasis disease-free and overall survival rates were 54% and 54%, respectively. The complications were as follows: gastrointestinal obstruction, 4 (24%); wound complications, 4 (24%); abscesses, 3 (18%); peripheral neuropathy, 3 (18%); rectovaginal fistula, 2 (12%); and ureteral obstruction, 2 (12%). CONCLUSION: Radical surgical resection and combined IORT for patients with recurrent gynecologic tumors seems to provide a reasonable local-control rate in patients who have failed prior surgery and/or definitive radiation. Patient selection is very important, however, as only those patients with complete gross resection at completion of surgery appear to benefit most from this radical approach in the salvage setting.     

Emergence of increased cerebral metastasis after high-dose preoperative radiotherapy with chemotherapy in patients with locally advanced nonsmall cell lung carcinoma.

BACKGROUND: In recent years, combined modality induction therapy has defined a new standard of care in the treatment of patients with American Joint Committee on Cancer (AJCC) Stage III nonsmall cell lung carcinoma, providing improved local control and improved disease-free survival. However, the majority of Stage III patients still die of recurrent disease. METHODS: Forty-two consecutive patients with AJCC Stage IIIA/IIIB nonsmall cell lung carcinoma (NSCLC) who were undergoing induction chemoradiotherapy followed by surgical resection of the primary NSCLC tumor between December 1, 1987 and September 1, 1999 were analyzed for resectability, survival, and patterns of disease failure. These patients received cisplatin (60 mg/m(2)) on Days 1 and 22 and etoposide (100 mg/m(2)) on Days 1, 2, and 3, and Days 22, 23, and 24 together with 5940 centigrays (cGy) of radiation in 180-cGy fractions delivered over 6 weeks. RESULTS: Thirty-one of the 42 patients (74%) underwent surgical resection of the primary lung tumor and mediastinal lymph nodes after chemoradiotherapy. No surgical deaths were reported. The median survival of these 31 patients was 52 months. The 5-year survival estimate using the Kaplan-Meier method was 49.9%. The local control rate was 80%. The incidence of distant metastases other than in the brain was reduced. The most frequently involved site of isolated first recurrence was the brain. The median time to brain recurrence was 7.5 months from the time of surgical resection. All brain metastases were detected within 2 years. CONCLUSIONS: The high incidence of isolated brain metastasis after induction chemoradiotherapy and curative resection and their response to treatment suggest that routine scans of the brain may be indicated in the follow-up of patients with locally advanced NSCLC.