Neoplasm Recurrence, Local
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Pubmed
Journal: Head & neck
January/23/2008
Abstract

BACKGROUND

Salivary duct carcinoma (SDC) is an aggressive tumor of the head and neck with a poor prognosis. The objective was to study SDC and recommend the use of trastuzumab as adjuvant therapy.

METHODS

A retrospective chart review of patients seen between 1993 and 2006 was performed. Tumor specimens were examined for HER-2 protein overexpression via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods.

RESULTS

Of the 7 patients with SDC, 57% had tumors arising in the parotid gland, the majority having facial nerve paralysis, 71% with nodal disease, and 43% having recurrence. All samples were HER-2 positive on IHC. Three patients had FISH-positive tumors, recurrent disease, and received trastuzumab therapy; 1 of the 3 died after 20 months and a second has shown disappearance of metastatic disease.

CONCLUSIONS

Trastuzumab is effective in treating HER-2-positive breast cancer. Given immunohistochemical similarities between SDC and ductal carcinoma of the breast, patients with FISH-positive HER-2/neu SDC should be considered for trastuzumab therapy.

Pubmed
Journal: The New England journal of medicine
February/24/2010
Abstract

BACKGROUND

The optimal fractionation schedule for whole-breast irradiation after breast-conserving surgery is unknown.

METHODS

We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule. Women with invasive breast cancer who had undergone breast-conserving surgery and in whom resection margins were clear and axillary lymph nodes were negative were randomly assigned to receive whole-breast irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of 35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period of 22 days (the hypofractionated-radiation group).

RESULTS

The risk of local recurrence at 10 years was 6.7% among the 612 women assigned to standard irradiation as compared with 6.2% among the 622 women assigned to the hypofractionated regimen (absolute difference, 0.5 percentage points; 95% confidence interval [CI], -2.5 to 3.5). At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, -6.9 to 9.8).

CONCLUSIONS

Ten years after treatment, accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who had undergone breast-conserving surgery for invasive breast cancer with clear surgical margins and negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.)

Pubmed
Journal: Cancer
August/23/2000
Abstract

BACKGROUND

Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors.

METHODS

After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early (</= 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed.

RESULTS

Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence.

CONCLUSIONS

Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.

Pubmed
Journal: The Journal of urology
February/9/2000
Abstract

OBJECTIVE

Partial nephrectomy is effective for renal cell carcinoma when preservation of renal function is a concern. We present the 10-year followup of patients treated with nephron sparing surgery at our institution.

METHODS

Partial nephrectomy was performed in 107 patients with localized sporadic renal cell carcinoma before December 1988. Tumors were symptomatic in 73 patients (68%) and indications for surgery were imperative in 96 (90%). Of the patients 42 (39%) had renal insufficiency preoperatively. All patients were followed a minimum of 10 years or until death.

RESULTS

At the end of the followup interval 32 patients (30%) had no evidence of recurrence, 28 (26%) died of metastatic renal cell carcinoma and 46 (42%) died of unrelated causes. Cancer specific survival was 88.2% at 5 and 73% at 10 years, and was significantly affected by tumor stage, symptoms, tumor laterality and tumor size. Long-term renal function was stable in 52 patients (49%).

CONCLUSIONS

Partial nephrectomy is effective for localized renal cell carcinoma, providing long-term tumor control with preservation of renal function.

Pubmed
Journal: Nature medicine
March/17/2014
Abstract

Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Downregulation of BMI-1 inhibits the ability of colorectal CICs to self-renew, resulting in the abrogation of their tumorigenic potential. Treatment of primary colorectal cancer xenografts with a small-molecule BMI-1 inhibitor resulted in colorectal CIC loss with long-term and irreversible impairment of tumor growth. Targeting the BMI-1-related self-renewal machinery provides the basis for a new therapeutic approach in the treatment of colorectal cancer.

Pubmed
Journal: Annals of surgery
September/1/1993
Abstract

OBJECTIVE

Currently, there is considerable controversy about the place of transplantation in the treatment of hepatocellular carcinoma (HCC). This study compared resection to transplantation in cirrhotic patients with HCC in order to determine reasonable indications of each treatment.

BACKGROUND

The usual procedure is to resect when feasible and to transplant in other cases.

METHODS

Three-year survival with and without recurrence was analyzed in 60 patients who underwent resection and 60 who underwent transplantation. Several prognostic factors, such as size, number of nodules, portal thrombus, and histologic form, were studied.

RESULTS

In terms of overall survival rates, resection and transplantation yield the same results (50% vs. 47%, respectively, at 3 years). For transplantation, however, the rate for survival without recurrence is better than that for resection (46% vs. 27%, respectively; p < 0.05). In the case of small uninodular or binodular tumors (< 3 cm), transplantation has much better results than resection (survival without recurrence, 83% vs. 18%, respectively; p < 0.001). However, it seems that a group of patients with high risk of recurrence after transplantation can be determined (diffuse form, more than two nodules > 3 cm, or presence of portal thrombus).

CONCLUSIONS

The best indication for transplantation seems to be patients with small and uninodular or binodular tumors; until now, these patients were considered to be the best candidates for resection. Patients undergoing transplantation for unresectable, large, multinodular or diffuse tumors seem to represent bad indications for transplantation. These results could help define reasonable indications for transplantation in an era with a shortage of liver grafts.

Pubmed
Journal: Gastroenterology
September/14/2009
Abstract

OBJECTIVE

Hepatocellular carcinoma (HCC) recurs in approximately 70% of cases after resection. Vascular invasion by tumor cells can be classified as gross or microscopic (microvascular invasion [mVI]) and is a risk factor for recurrence. We examined a large cohort of patients with HCC who were treated by resection to identify features of mVI that correlated with recurrence and survival.

METHODS

We reviewed the records of all HCC resections performed at the Mount Sinai School of Medicine between January 1990 and March 2006 to identify those with mVI, established by histologic analysis. The numbers and sizes of vessels invaded, invasion of a vessel with a muscular wall, distance from the tumor, and satellite nodules were recorded.

RESULTS

Of the 384 patients who underwent resection for HCC, 131 (34.1%) met the entry criteria. The median follow-up period was 28.9 months. There were 68 recurrences and 54 deaths. In multivariate analysis, invasion of a vessel with a muscular wall predicted recurrence (hazard ratio, 1.8; P = .02), and invasion of a vessel with a muscular wall (hazard ratio, 2.2; P = .018) and invasion of a vessel that was more than 1 cm from the tumor (hazard ratio, 2.1; P = .015) predicted survival. A risk score that assigned points for the presence of each variable correlated with recurrence (P = .028) and survival (P < .0001).

CONCLUSIONS

A novel classification system that includes invasion of a vessel with a muscular wall and invasion of a vessel that is more than 1 cm from the tumor can accurately predict risk of recurrence and survival of patients with mVI after resection of HCC.

Pubmed
Journal: Lancet (London, England)
February/28/2007
Abstract

BACKGROUND

Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival.

METHODS

4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920.

RESULTS

After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded.

CONCLUSIONS

Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.

Pubmed
Journal: Cancer cell
June/27/2004
Abstract

The prognostication of head and neck squamous cell carcinoma (HNSCC) is largely based upon the tumor size and location and the presence of lymph node metastases. Here we show that gene expression patterns from 60 HNSCC samples assayed on cDNA microarrays allowed categorization of these tumors into four distinct subtypes. These subtypes showed statistically significant differences in recurrence-free survival and included a subtype with a possible EGFR-pathway signature, a mesenchymal-enriched subtype, a normal epithelium-like subtype, and a subtype with high levels of antioxidant enzymes. Supervised analyses to predict lymph node metastasis status were approximately 80% accurate when tumor subsite and pathological node status were considered simultaneously. This work represents an important step toward the identification of clinically significant biomarkers for HNSCC.

Pubmed
Journal: Cancer
May/19/2003
Abstract

BACKGROUND

The objective of this study was to determine the clinical characteristics, treatment response, and frequency of p53 overexpression in Ashkenazi Jewish women with hereditary ovarian carcinoma.

METHODS

Seventy-one Jewish women with epithelial ovarian carcinoma (EOC) were tested for the three BRCA founder mutations using single-strand conformation polymorphism analysis, heteroduplex analysis, and protein truncation testing. Clinical and histopathologic data were reviewed retrospectively. In vitro chemoresistance was analyzed in 32 patients. Mutations of p53 were studied using immunohistochemical detection of p53 overexpression.

RESULTS

Thirty-four of 71 Jewish patients with EOC (48%) had germline BRCA mutations (BRCA heterozygotes), including 22 BRCA1 mutations and 12 BRCA2 mutations. BRCA heterozygotes were younger compared with Jewish patients who had EOC without mutations (sporadic carcinoma; 50 years vs. 59 years, respectively; P = 0.01). BRCA1 heterozygotes were younger compared with BRCA2 heterozygotes (48 years vs. 57 years, respectively; P = 0.01). Histopathologic tumor features were similar; however, tumors with low malignant potential were seen only in women with sporadic carcinoma. Both groups had equivalent rates of surgical cytoreduction and similar median follow-up (72 months). BRCA heterozygotes had higher response rates to primary therapy compared with patients who had sporadic disease (P = 0.01). In vitro chemoresistance predicted tumor response to platinum chemotherapy correctly in BRCA heterozygotes (P = 0.0096). BRCA heterozygotes with advance-stage disease had improved survival compared with patients who had advanced stage sporadic carcinoma (91 months vs. 54 months, respectively; P = 0.046) and had a longer disease free interval (49 months vs. 19 months, respectively; P = 0.16). p53 overexpression was common in BRCA heterozygotes (80%).

CONCLUSIONS

BRCA1 heterozygotes developed EOC at a younger age compared with BRCA2 heterozygotes and women who had sporadic ovarian carcinoma. BRCA heterozygotes had a better response to platinum chemotherapy compared with women who had sporadic disease, which may have contributed to their improved prognosis.

Pubmed
Journal: The Journal of urology
September/2/2004
Abstract

OBJECTIVE

Laparoscopic partial nephrectomy (LPN) has emerged as a viable alternative to open surgery for renal tumors less than 4 cm. We present oncological followup of patients treated with laparoscopic nephron sparing surgery at our institution.

METHODS

Between September 1996 and December 2001, 48 patients who underwent LPN for clinically localized tumors were found to have pathologically proven renal cell carcinoma. Medical and operative records were reviewed for clinical characteristics, pathological findings and followup information.

RESULTS

Mean patient age was 59.7 years (range 32 to 81) and mean followup was 37.7 months (range 22 to 84). Mean tumor size was 2.4 cm (range 1.0 to 4.0). Final pathological stage was pT1 in 42 patients (87.5%) and pT3a in 6 (12.5%). Histology revealed clear cell in 32 patients (66.7%), papillary in 10 (20.8%), chromophobe in 3 (6.3%), collecting duct in 1 (2.1%) and unclassified in 2 (4.2%). Intraoperative frozen section biopsies revealed negative margins in all cases. Final surgical margins were positive in 1 patient (2.1%). Followup evaluation consisting of physical examination and yearly cross-sectional imaging, which revealed no recurrences in 46 of 48 patients (95.8%). One patient with von Hippel-Lindau disease was found to have local recurrence 18 months after LPN and observation was elected. The second patient had recurrence in the same kidney away from the original tumor site approximately 4 years later.

CONCLUSIONS

LPN is an effective treatment modality for clinically localized renal cell carcinoma. Oncological outcomes at a mean followup of 3 years are promising, although the durability of oncological outcomes must be determined.

Pubmed
Journal: The oncologist
March/21/2005
Abstract

Breast cancer is the most common malignancy among American women. Due to increased screening, the majority of patients present with early-stage breast cancer. The Oxford Overview Analysis demonstrates that adjuvant hormonal therapy and polychemotherapy reduce the risk of recurrence and death from breast cancer. Adjuvant systemic therapy, however, has associated risks and it would be useful to be able to optimally select patients most likely to benefit. The purpose of adjuvant systemic therapy is to eradicate distant micrometastatic deposits. It is essential therefore to be able to estimate an individual patient's risk of harboring clinically silent micrometastatic disease using established prognostic factors. It is also beneficial to be able to select the optimal adjuvant therapy for an individual patient based on established predictive factors. It is standard practice to administer systemic therapy to all patients with lymph node-positive disease. However, there are clearly differences among node-positive women that may warrant a more aggressive therapeutic approach. Furthermore, there are many node-negative women who would also benefit from adjuvant systemic therapy. Prognostic factors therefore must be differentiated from predictive factors. A prognostic factor is any measurement available at the time of surgery that correlates with disease-free or overall survival in the absence of systemic adjuvant therapy and, as a result, is able to correlate with the natural history of the disease. In contrast, a predictive factor is any measurement associated with response to a given therapy. Some factors, such as hormone receptors and HER2/neu overexpression, are both prognostic and predictive.

Pubmed
Journal: Gene therapy
August/3/2000
Abstract

The herpes simplex virus (HSV) ICP34.5 null mutant 1716 replicates selectively in actively dividing cells and has been proposed as a potential treatment for cancer, particularly brain tumours. We present a clinical study to evaluate the safety of 1716 in patients with relapsed malignant glioma. Following intratumoural inoculation of doses up to 10(5) p.f.u., there was no induction of encephalitis, no adverse clinical symptoms, and no reactivation of latent HSV. Of nine patients treated, four are currently alive and well 14-24 months after 1716 administration. This study demonstrates the feasibility of using replication-competent HSV in human therapy.

Pubmed
Journal: European urology
October/22/2003
Abstract

BACKGROUND

The evaluation of the efficacy of the treatment of men with prostate cancer is largely based on post treatment levels of PSA. An increase in PSA or biochemical recurrence is the first sign of recurrent disease and precedes a clinically detectable recurrence by months to years. Digital rectal examination and conventional imaging techniques are not sensitive to detect a local recurrence. A metabolic imaging technique, which is not dependent on anatomical distortions, could be of use. In this study we investigated 11C-choline positron emission tomography (PET) for the evaluation after treatment of localized prostate cancer.

METHODS

Thirty-six patients with localized prostate cancer, treated by either radical prostatectomy (n=20) or by external beam radiotherapy (n=16) were studied with 11C-choline PET. The results of PET were compared with the results of histology and with clinical follow up.

RESULTS

Fourteen patients had no biochemical failure after therapy. 11C-choline PET was true negative in 14/14 patients. Twenty-two patients had a biochemical failure. In the radical prostatectomy patients 11C-choline PET was true positive in 5/13 (38%) cases. In the external beam radiotherapy patients 11C-choline PET was true positive in 7/9 (78%). The recurrent tumor was confirmed by biopsy or by bone scan in eleven of the twelve true positive patients. In ten patients with a negative 11C-choline PET scan, no recurrent tumor could be proven yet clinically, by biopsy or during follow up.

CONCLUSIONS

11C-choline PET is a feasible technique for evaluation of treatment for localized prostate cancer. The site of recurrence was detected correctly in 78% of the patients after external beam radiotherapy compared to 38% of the patients after radical prostatectomy. No positive PET scans were observed sofar in patients with a serum PSA <5ng/ml. Confirmatory studies and longer follow up are needed to determine the efficacy of 11C-choline PET compared to other imaging techniques.

Pubmed
Journal: Surgery
February/23/2004
Abstract

BACKGROUND

Several factors have been proven to be useful for classifying patients with papillary thyroid carcinoma (PTC) into either low- or high-risk groups. However, the relative importance of prognostic factors, including lymph nodal metastasis, remains unclear.

METHODS

A total of 604 patients who underwent initial surgery for PTC (diameter of tumor>1 cm) were analyzed. The mean duration of follow-up was 10.7 years.

RESULTS

By multivariate analysis for disease-specific survival, distant metastasis was the only significant risk factor (risk ratio=65.1) for younger patients (age<50). For older patients (age> or =50), distant metastasis (risk ratio=6.7), extrathyroidal invasion (risk ratio=2.4), and large nodal metastasis (> or =3 cm; risk ratio=5.3) had relative importance. From the results, younger patients with distant metastasis and older patients with any of the 3 factors were defined as at high risk, whereas the other patients were defined as at low risk. Overall, 106 patients at high risk (18%) and 498 patients at low risk (83%) had 10-year survival rates of 69% and 99%, respectively. Only 3 patients of the low-risk group died from the disease. Among postoperative factors, recurrence within 3 years after initial surgery was the most important risk factor for cancer death. Of the high-risk group, patients with a disease-free interval of >3 years showed an excellent outcome (96% of a 10-year survival rate), similar to patients in the low-risk group.

CONCLUSIONS

A novel classification system, in which large nodal metastases and postoperative reclassification were added, was devised. This was useful for choosing proper therapeutic strategies, offering rational information, and determining adequate postoperative follow-up schemes for individual patients with PTC.

Pubmed
Journal: Nature reviews. Cancer
January/10/2011
Abstract

The increasing number of cancer survivors is cause for celebration, but this expanding population has highlighted the problem of tumour dormancy, which can lead to relapse. As we start to understand more about the biology of dormant cancer cells, we can begin to address how best to treat this form of disease. Preclinical models and initial clinical trials, as exemplified in patients with breast cancer, are paving the way to address how best to treat long-term cancer survivors to minimize the risk of cancer recurrence.

Pubmed
Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
February/24/2009
Abstract

Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC <or= 5 cm or less than or equal to three HCCs <or= 3 cm. We prospectively evaluated the possibility of slightly extending these criteria in a down-staging protocol, which included patients initially outside conventional criteria: single HCC 5-6 cm or two HCCs <or= 5 cm or less than six HCCs <or= 4 cm and sum diameter <or= 12 cm, but within Milan criteria in the active tumors after the down-staging procedures. The outcome of patients down-staged was compared to that of Milan criteria after liver transplantation and since the first evaluation according to an intention-to-treat principle. From 2003 to 2006, 177 patients with HCC were considered for transplantation: the transplantation rate was comparable between the Milan and down-staging groups: 88/129 cases (68%) versus 32/48 cases (67%), respectively. At a median follow-up of 2.5 years after transplantation, the 1 and 3 years' disease-free survival rates were comparable: 80% and 71% in the Milan group versus 78% and 71% in the down-staging. The actuarial intention-to-treat survival was 27/48 patients (56.3%) in the down-staging and 81/129 cases (62.8%) in the Milan group, p = n.s. The proposed down-staging criteria provide a comparable outcome to the conventional criteria.

Pubmed
Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
November/26/2007
Abstract

Malignant gliomas and metastatic tumors are the most common brain tumors. Neuroimaging plays a significant role clinically. In low-grade tumors, neuroimaging is needed to evaluate recurrent disease and to monitor anaplastic transformation into high-grade tumors. In high-grade and metastatic tumors, the imaging challenge is to distinguish between recurrent tumor and treatment-induced changes such as radiation necrosis. The current clinical gold standard, MRI, provides superior structural detail but poor specificity in identifying viable tumors in brain treated with surgery, radiation, or chemotherapy. (18)F-FDG PET identifies anaplastic transformation and has prognostic value. The sensitivity and specificity of (18)F-FDG in evaluating recurrent tumor and treatment-induced changes can be improved significantly by co-registration with MRI and potentially by delayed imaging 3-8 h after injection. Amino acid PET tracers are more sensitive than (18)F-FDG in imaging recurrent tumors and in particular recurrent low-grade tumors. They are also promising in differentiating between recurrent tumors and treatment-induced changes.

Authors
Pubmed
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
August/10/2010
Abstract

OBJECTIVE

The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.

METHODS

Women > or = 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m(2) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2) every 3 weeks or PLD 50 mg/m(2) every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.

RESULTS

Patients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.

CONCLUSIONS

When combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.

Pubmed
Journal: The Journal of urology
April/5/2005
Abstract

OBJECTIVE

We evaluated the incidence and risks of urethral recurrence following radical cystectomy and urinary diversion in men with transitional cell carcinoma of the bladder.

METHODS

Clinical and pathological results were evaluated in 768 consecutive male patients undergoing radical cystectomy with intent to cure for bladder cancer with a median followup 13 years, including 397 (51%) who underwent orthotopic urinary diversion with a median followup of 10 years and 371 (49%) who underwent cutaneous urinary diversion with a median followup of 19 years. Demographically and clinically these 2 groups were well matched with the only exception being longer median followup in the cutaneous group (p <0.001). Urethral recurrence was analyzed by univariate and multivariable analysis according to carcinoma in situ, tumor multifocality, pathological characteristics (tumor grade, stage and subgroup), the presence and extent of prostate tumor involvement (superficial vs stromal invasion) and the form of urinary diversion (cutaneous vs orthotopic).

RESULTS

A total of 45 patients (6%) had urethral recurrence at a median of 2 years (range 0.2 to 13.6), including 16 (4%) with an orthotopic and 29 (8%) with a cutaneous form of urinary diversion. Carcinoma in situ and tumor multifocality were not significantly associated with an increased risk of urethral recurrence (p = 0.07 and 0.06, respectively). The presence of any (superficial and/or stromal invasion) prostatic tumor involvement was identified in 129 patients (17%). Prostate tumor involvement was associated with a significantly increased risk of urethral recurrence (p = 0.01). The estimated 5-year chance of urethral recurrence was 5% without any prostate involvement, increasing to 12% and 18% with superficial and invasive prostate involvement, respectively. Patients undergoing orthotopic diversion demonstrated a significantly lower risk of urethral recurrence compared with those undergoing cutaneous urinary diversion (p = 0.02). Patients without any prostate tumor involvement and orthotopic diversion (lowest risk group) demonstrated an estimated 4% year chance of urethral recurrence compared with a 24% chance in those with invasive prostate involvement undergoing cutaneous diversion (highest risk group). On multivariate analysis any prostate involvement (superficial and/or invasive) and urinary diversion form remained independent and significant predictors of urethral recurrence (p = 0.035 and 0.01, respectively).

CONCLUSIONS

At long-term followup urethral tumor recurrence occurs in approximately 7% of men following cystectomy for bladder transitional cell carcinoma. Involvement of the prostate with tumor and the form of urinary diversion were significant and independent risk factors for urethral tumor recurrence. Patients undergoing orthotopic diversion have a lower incidence of urethral recurrence compared with those undergoing cutaneous diversion. Although prostate tumor involvement is a risk factor for urethral recurrence, it should not preclude orthotopic diversion, provided that intraoperative frozen section analysis of the urethral margin is without evidence of tumor.

Pubmed
Journal: Cancer
May/28/2003
Abstract

BACKGROUND

Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm. Despite a consensus for the distinct clinicopathologic entity of EMC, its clinical features remain controversial. In addition, most studies have contained a small number of patients who underwent definitive surgical treatment.

METHODS

Forty-two cases of EMC, which had been identified from files of eight affiliated hospitals and confirmed for histologic diagnosis at the Pathology Center, were analyzed for histologic grade, demographics, treatments, outcomes, and prognostic factors. The average follow-up period was 7.4 years.

RESULTS

Included in the study were 20 men and 22 women with a mean age at diagnosis of 52.1 years. The tumors were located mainly in the lower extremities (69%). Thirty-three tumors (79%) were classified as Grade 1 and nine as Grade 2 according to the modified French System. Overall survival was 100% at 5 years and 88% at 10 years. Disease-free survival was 45% at 5 years and 36% at 10 years. Inadequate initial surgery was defined as a significant risk factor for local recurrence by univariate analysis of all 42 patients but not by the analysis of those 30 patients who had undergone wide tumor excision or amputation. Wide excision led to the recurrence rate of 14%.

CONCLUSIONS

These findings supported the role of wide excision in the local control of EMC, irrespective of the previous excision procedure or recurrence. The protracted clinical course of the tumors and the presence of patients who had distant metastasis develop after definitive surgery of the primary tumor represented EMC as intermediate malignancy.

Pubmed
Journal: Annals of surgical oncology
October/23/2006
Abstract

BACKGROUND

Recent experimental evidence has shown a potential role of interleukin (IL)-11 and its receptor in breast cancer development and progression. However, there is little clinical information to support this hypothesis. We examined the expression of IL-11 and its receptor in primary breast cancer tissue samples and correlated their level of expression with the clinical outcome.

METHODS

Primary breast cancer samples (n=109) and matched background tissue obtained from patients in the cohort (n=33) were processed for frozen section and RNA extraction. Frozen sections from matched tissues were immunostained with IL-11 and IL-11 receptor antibodies. Staining intensity was analyzed by computer image analysis. RNA was reverse-transcribed and quantified before analysis by quantitative polymerase chain reaction. Results were expressed as the number of transcripts (standardized by beta-actin). The data were compared with the clinical outcome of the disease.

RESULTS

The intensity of staining for both IL-11 and the IL-11 receptor was distinctly high in tumor samples (P<.01). The transcript level of IL-11 was significantly higher in node-positive tumor samples compared with node-negative samples (P=.02). Tumors with a poor prognostic index and poor histological grade showed a higher level of IL-11. A higher level of IL-11 was linked to poorer survival with Kaplan-Meier survival analysis.

CONCLUSIONS

IL-11 can be a predictor of poor prognosis in human breast cancer.

Pubmed
Journal: The Journal of clinical endocrinology and metabolism
June/6/2006
Abstract

OBJECTIVE

Transsphenoidal surgery is the treatment of choice for nonfunctioning pituitary macroadenomas (NFMA). In this study we evaluated the long-term effects of a treatment strategy in which postoperative radiotherapy was not routinely applied to patients with NFMA.

METHODS

This was a retrospective follow-up study.

METHODS

We included 109 consecutive patients (age 56 +/- 13 yr) operated for NFMA between 1992 and 2004.

RESULTS

Radiological imaging revealed a macroadenoma in all patients, with suprasellar extension in 96% and parasellar/infrasellar extension in 36% of cases. Visual field defects were present in 87% of the patients and improved in 84% of these patients after surgery. Only six patients received postoperative radiotherapy. Ten patients died during the follow-up period. Ninety-seven patients could be assessed for tumor regrowth or tumor recurrence after a mean follow-up period of 6.0 +/- 3.7 yr. In nine patients there was evidence for tumor regrowth, and in one patient tumor recurrence was observed. The mean time to tumor growth/recurrence after initial therapy was 6.9 (range 3-12) yr. Follow-up duration was found to be an independent predictor for tumor regrowth.

CONCLUSIONS

Transsphenoidal surgery without postoperative radiotherapy is an effective and safe treatment strategy for NFMA, without evidence for tumor regrowth in 90% of all patients, at least for the duration of follow-up presented in this study. Additional studies are required to exclude higher regrowth and recurrence rates during prolongation of the duration of follow-up.

Pubmed
Journal: The Journal of urology
July/26/2006
Abstract

OBJECTIVE

We studied prognostic factors for 5-year disease specific and recurrence-free survival in patients treated for upper urinary tract transitional cell carcinoma.

METHODS

Since July 1987, 72 patients with a mean age of 58.9 years have undergone nephroureterectomy with bladder cuff excision. Median followup was 62.2 months (range 6 to 192). Patient age, sex, detection duration and mode, bladder tumor history, smoking habit, stone disease history, and tumor stage, grade and location were evaluated as prognostic factors.

RESULTS

Overall 5-year disease specific and recurrence-free survival rates were 74.9% and 67.8%, respectively. Univariate analysis revealed anemia, positive bladder tumor history, T stage, grade and tumor location in the upper tract as significant prognostic factors. On multivariate analysis T stage, grade and tumor location in the urothelium were the only significant variables for the 5-year disease specific and recurrence-free survival rates.

CONCLUSIONS

High tumor stage and grade, and ureteral location were significantly associated with worse disease specific and recurrence-free survival in patients with upper urinary tract transitional cell carcinoma. Our results may help define the patient groups that need adjuvant therapy and they may form a basis for further controlled studies.

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