Biomedical subjects

Ennapadam Venkatraman

Publications and source records attributed to Ennapadam Venkatraman.

At least 19 recordsLinked to original sources

PubMed2004

Intensity-modulated radiotherapy for soft tissue sarcoma of the thigh.

PURPOSE: Fracture of the femur is one of the late complications of adjuvant radiotherapy for patients with soft tissue sarcomas of the thigh, who receive external beam irradiation after limb-sparing surgery. When the target volume approximates the femur, it is often inevitable that a large segment of the femur will receive full prescription dose with conventional radiation techniques. We report the dosimetric feasibility of intensity- modulated radiation therapy (IMRT) techniques to achieve adequate target coverage and bone sparing. METHODS AND MATERIALS: Treatment planning was performed using both three-dimensional conformal radiotherapy (3D-CRT) and IMRT techniques for 10 patients with soft tissue sarcoma of the thigh with tumor approaching the femur. None of the patients had bony involvement. For all patients, the gross total volume (GTV) and the femur were contoured. The clinical target volume (CTV) was defined as the GTV with a 1.5-cm margin axially, except at the bone interface where the bone interface was used as CTV if the 1.5-cm axial margin extended beyond the bone interface. In the superior-inferior direction, the CTV margin placed around the GTV varied from 5 to 10 cm. The planning target volume (PTV) was defined as the CTV with 5-mm margin all around. The 3D conformal technique consisted primarily of two to three beams with wedges or partial transmission blocks as compensators. For the IMRT technique, five coplanar beams were used, chosen so as to spare much of the surrounding soft tissue and to clear the other extremity or groin areas. IMRT plans were designed to adequately treat the planning target volume and spare the femur as much as possible. RESULTS: Dose distributions and dose-volume histograms were analyzed. PTV coverage was comparable with both IMRT and 3D-CRT plans. Dose distributions were more conformal with IMRT, however, especially for patients with large variations of contours. The volume of the femur receiving at least full prescription (63 Gy) V100 decreased on average by approximately 57%, from 44.7 +/- 16.8% with 3D-CRT to 18.6 +/- 9.2% with IMRT (p < 0.01). For 3 patients with a GTV surrounding <50% of the circumference of the femur, the reduction in the V100 to the femur ranged from 61% to 79%. The hot spots in the femur, as measured by D05 (the dose encompassing 5% of volume), reduced on average from 67.2 +/- 1.8 Gy with 3D-CRT to 65.0 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the femur was on average 38.5 +/- 11.5 Gy with IMRT, compared with 40.9 +/- 12.7 Gy with 3D-CRT. The volume of the surrounding soft tissues, defined as the ipsilateral limb excluding the PTV and the femur, receiving at least prescription dose (63 Gy) was reduced on average by about 78%, from 997 +/- 660 cc with 3D-CRT to 201 +/- 144 cc with IMRT (p < 0.01). The D05 to the surrounding soft tissues was on average 58.7 +/- 4.7 Gy with IMRT, compared to 67.8 +/- 1.3 Gy with 3D-CRT (p < 0.01), a reduction of approximately 13%. The mean dose to the surrounding soft tissues was comparable in both plans. The volume of the skin (from surface to 5 mm depth) receiving prescription dose (63 Gy) declined by roughly 45%, from 115 +/- 40 cc with 3D-CRT to 61 +/- 20 cc with IMRT (p < 0.01), with IMRT providing full skin dose coverage to scars. The hot spots in the skin decreased from 68.0 +/- 1.7 Gy with 3D-CRT to 65.2 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the skin lessened from 51.5 +/- 4.7 Gy with 3D- CRT to 44.0 +/- 4.2 Gy with IMRT (p < 0.01), a reduction of 14%. CONCLUSIONS: Intensity-modulated radiation therapy techniques can reduce the dose to the femur without compromising target coverage by achieving concave dose distributions around the interface of the PTV and the femur. At the same time, IMRT can reduce the hot spots significantly in the surrounding soft tissues and skin. Whether such dosimetric improvements can translate into reduction of complications and/or improving local control needs to be investigated.

Femur↗

PubMed2004

Intraperitoneal cisplatin with intraperitoneal gemcitabine in patients with epithelial ovarian cancer: results of a phase I/II Trial.

PURPOSE: The aims of this study were to determine the dose and schedule of i.p. cisplatin with i.p. gemcitabine in patients with persistent disease at second-look assessment, the toxicity of this regimen, and the time to treatment failure and overall survival. EXPERIMENTAL DESIGN: We performed a Phase I/II evaluation of i.p. cisplatin at 75 mg/m(2) on day 1 with planned gemcitabine at 500, 750, 1000, or 1250 mg/m(2) i.p. on days 1, 8, and 15 on a 28-day schedule for four courses. Eligible patients completed surgical cytoreduction followed by adjuvant platinum-based chemotherapy. They had second-look assessment showing microscopic or macroscopic (< or =1 cm) disease, followed by i.p. port placement. RESULTS: The Phase I dose-limiting toxicity was grade 3 thrombocytopenia at day 15 on dose level 1 (n = 5). The protocol was amended, and the Phase II portion accrued to 30 patients, who were given i.p. cisplatin (75 mg/m(2)) on day 1 and gemcitabine at 500 mg/m(2) on days 1 and 8 on a 21-day schedule for four courses. Nine patients were removed from the study: one each for hypersensitivity, cellulitis, and i.p. port malfunction; two for progression of disease; and four for renal toxicity. Other toxicities included grade 3 nausea (7%) and transient grade 3 neuropathy (3%). Grade 1 or 2 neuropathy was frequently seen (80%). Five patients (17%) returned to the operating room at a median of 6 months (range, 1-20 months) after i.p. therapy for evaluation of abdominal pain; two patients had recurrence, and all had areas of fibrous tissue with encasement of the bowel. In two patients, the fibrous tissue was causing partial bowel obstruction. No other patients had symptoms prompting surgical exploration. Pharmacokinetic (PK) studies showed a median area under the curve (AUC) i.p. of 3041 h. micro M (range, 676-5702 h. micro M) and AUC in plasma of 4.0 h. micro M (range, 0.92-8.2 h. micro M) reached between 120 and 240 min; the pharmacological advantage was 759-fold (range, 217-1415-fold) for i.p. versus plasma drug levels. The mean residence time of gemcitabine with i.p. administration was 4.7 h. The median time to progression of the intent to treat population was 15.93 months (95% confidence interval, 9.13-25.9 months), with a median overall survival of 43.5 months [95% confidence interval, (34.66- infinity)]. No statistical differences were seen with respect to overall survival if patients were grouped in terms of optimal debulking or not (median not reached versus 34.8 months, respectively; P = 0.16) or whether visible disease was present or not at the start of i.p. therapy (34.8 versus 47.7 months; P = 0.47). With regard to time to treatment failure, a statistical difference favored patients with optimal versus nonoptimal primary debulking (25.2 versus 10.2 months, respectively; P = 0.03). CONCLUSIONS: The median time to treatment failure and overall survival of 15.9 months and 43.5 months, respectively, are consistent with our historical data in patients receiving i.p. platinum-based regimens for consolidation. The fibrotic changes seen in explored patients suggest local toxicity of this combination. The absolute benefit of i.p. consolidation requires randomized trials to assess efficacy.

Adult↗

PubMed2004

Using patients as their own controls for cost evaluation of phase I clinical trials.

PURPOSE: Little is known about the cost of phase I trials in cancer patients compared with that of standard treatments, yet the former is often assumed to be greater than the latter. Our objective was to utilize a new approach, using patients as their own controls, to compare in a pilot study the costs of care for patients on phase I trials with those incurred for standard treatment. PATIENTS AND METHODS: We retrospectively assessed the direct medical costs (DMCs) of 59 patients participating in one of two phase I trials (TRIAL) in solid tumors conducted at Memorial Hospital (MH): (1). perillyl alcohol, and (2). flavopiridol with paclitaxel. Paired-control DMCs were those accrued by the same patient while receiving standard chemotherapy regimens just before (PRE; n = 41) or after (POST; n = 29) the trial at MH, averaged per day. RESULTS: For the 41 PRE patients, the median and mean DMCs per day for the clinical trial versus standard treatment were (US dollars) US dollars 123 v US dollars 133 and US dollars 219 v US dollars 267, respectively. For the 29 POST patients, the median and mean DMCs for the clinical trial versus standard treatment were US dollars 157 v US dollars 152 and US dollars 226 v US dollars 226, respectively. Using a linear mixed model, there was no significant difference between TRIAL and standard treatment DMCs (P =.54). CONCLUSION: Using patients as their own controls represents a new, efficient method for evaluating the cost of phase I trials, and it warrants further study. The results of our pilot study do not suggest that phase I trials always cost payers more than standard treatment.

Adult↗

PubMed2004

Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer.

PURPOSE: Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non-small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib. PATIENTS AND METHODS: We reviewed medical records, pathologic material, and imaging studies of all 139 NSCLC patients treated on one of three consecutive studies of gefitinib monotherapy performed at our institution. We identified patients experiencing a major objective response and compared their clinical and pathologic features with the others. Univariate and multivariable analyses were performed on potential predictive features associated with sensitivity to gefitinib. RESULTS: Of 139 patients, 21 (15%; 95% CI, 9% to 21%), experienced a partial radiographic response. Variables identified as significant in univariate analysis included adenocarcinoma versus other NSCLC (19% v 0%; P=.004), adenocarcinoma with bronchioloalveolar features versus other adenocarcinomas (38% v 14%; P<.001), never smoker status versus former/current (36% v 8%; P<.001), and Karnofsky performance status > or =80% versus < or =70% (22% v 8%; P=.03). Multivariable analysis revealed the presence of adenocarcinoma with any bronchioloalveolar features (P=.004) and being a never smoker (P=.006) were independent predictors of response. CONCLUSION: Our data suggest that individuals in whom gefitinib is efficacious are more likely to have adenocarcinomas of the bronchioloalveolar subtype and to be never smokers. These observations may provide clues to mechanisms determining sensitivity to this agent and suggest that NSCLC has a different biology in patients who never smoked and those with bronchioloalveolar carcinoma.

Adult↗

PubMed2004

Clinicopathologic analysis of early-stage sporadic ovarian carcinoma.

The reported experience with early-stage (FIGO stage I/II) ovarian carcinoma (OC) is limited given that the majority of women with OC are diagnosed at an advanced stage. There has not been an extensive review of these tumors, and since the pathologic criteria differentiating invasive and borderline tumors have evolved over time, the issue of whether a proportion of these tumors should be reclassified has not been addressed. We identified patients with stage I/II invasive OC who underwent primary surgical management at Memorial Sloan-Kettering Cancer Center from 1980 to 2000. Patients known to have a BRCA mutation or a family history of breast/ovarian cancer were excluded. Hematoxylin and eosin slide review, blinded to clinical outcomes, using current diagnostic criteria for ovarian carcinomas and borderline ovarian tumors, was performed. Progression-free survival (PFS) and disease-specific survival (DSS) were estimated and compared. Hematoxylin and eosin slides were reviewed for 140 of the 145 patients identified. The diagnosis was changed to borderline (low malignant potential) in 41 cases (29.3%). Twenty-nine (70.7%) of 41 changes in diagnosis involved endometrioid and mucinous tumors. This was attributable to the application of recently revised criteria for distinguishing borderline tumors from carcinomas. None of the originally diagnosed clear cell carcinomas was reclassified as borderline. The distribution of histologic subtypes among the 94 carcinomas included 26 serous (27.7%), 25 clear cell (26.6%), 22 endometrioid (23.4%), 10 mixed (10.6%), 6 mucinous (6.4%), 2 malignant Brenner (2.1%), and 3 adenocarcinomas, not otherwise specified (3.2%). Adjuvant therapy was given to 84 (89.4%) of the 94 patients with carcinomas. The 5-year PFS and DSS were significantly greater for the group of cases that was reclassified as borderline (4.5% vs. 26.2% progressed [P = 0.006]; 4.5% vs. 25.6% died [P = 0.003]). The 5-year PFS and DSS were significantly worse for carcinomas with a TP53 mutation (22.6% vs. 41.2% progressed [P = 0.04]; 21.7% vs. 24.7% died [P = 0.04]). There were no statistically significant differences in outcome between stages I versus II, tumor grades, clear cell histology versus other, and stage IC preoperative versus intraoperative rupture. We concluded that a large number of cases originally diagnosed as early-stage sporadic OC were borderline tumors. Clear cell histology does not confer a worse prognosis compared with other histologies. The presence of a TP53 mutation was an adverse prognostic indicator.

Adult↗

PubMed2003

Is endometrial carcinoma intrinsically more aggressive in elderly patients?

BACKGROUND: The current study was conducted to determine the influence of old age (age >/= 70 years) on outcome in a group of patients with endometrial carcinoma who were treated with simple hysterectomy followed by adjuvant radiation therapy (RT). METHODS: Between November 1987 and May 2000, 405 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB-II endometrial carcinoma were treated with postoperative RT. Intravaginal RT alone was given to 77% of patients (median dose, 21grays [Gy] given in 3 fractions). Additional postoperative external beam radiation therapy (EBRT) was given to 23% of patients (median dose, 45 Gy). Eighty-four patients were age >/= 70 years and 321 patients were age < 70 years. The two groups were well balanced with regard to race, comprehensive surgical staging, aggressive histology, lymphovascular invasion, lower uterine segment involvement, cervical involvement, and the use of postoperative EBRT. Significantly more patients in the age >/= 70 years group had other comorbidities such as obesity, diabetes mellitus, or hypertension (P = 0.02) and were found to have deep (> 50%) myometrial invasion (P = 0.008). RESULTS: With a median follow-up time of 48 months, the 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were 95%, 91%, and 90% respectively. On multivariate analysis, poor LRC was found to be correlated with age >/= 70 years (P = 0.019) and lymphovascular invasion (P = 0.001). Poor DFS was found to be correlated with age >/= 70 years (P = 0.03), lymphovascular invasion (P = 0.01), and aggressive histology (P = 0.001). Similarly, poor OS was found to correlate with age >/= 70 years (P = 0.001), lymphovascular invasion (P = 0.01), aggressive histology (P = 0.01), and cervical involvement (P = 0.02). The same factors that were found to correlate with OS (age >/= 70 years, lymphovascular involvement, aggressive histology, and cervical involvement) also appeared to correlate with disease-specific survival (P = 0.03, P = 0.008, P = 0.001, and P = 0.04, respectively). The 5-year actuarial rates of Radiation Therapy Oncology Group late complications that were >/= Grade 3 (gastrointestinal tract, genitourinary tract, or vagina) were 3% in both groups. CONCLUSIONS: Even when treated in a similar fashion, endometrial carcinoma patients age >/= 70 years appear to fare worse than younger patients independent of other poor prognostic factors. The rate of complications from adjuvant RT, despite a higher rate of comorbidity in elderly patients, was found to be similar in both age groups. Endometrial carcinoma appears to be intrinsically more aggressive in older patients, thus mandating further improvement in their treatment strategies.

Adult↗

PubMed2003

Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation.

We have developed a methodology we call ROMA (representational oligonucleotide microarray analysis), for the detection of the genomic aberrations in cancer and normal humans. By arraying oligonucleotide probes designed from the human genome sequence, and hybridizing with "representations" from cancer and normal cells, we detect regions of the genome with altered "copy number." We achieve an average resolution of 30 kb throughout the genome, and resolutions as high as a probe every 15 kb are practical. We illustrate the characteristics of probes on the array and accuracy of measurements obtained using ROMA. Using this methodology, we identify variation between cancer and normal genomes, as well as between normal human genomes. In cancer genomes, we readily detect amplifications and large and small homozygous and hemizygous deletions. Between normal human genomes, we frequently detect large (100 kb to 1 Mb) deletions or duplications. Many of these changes encompass known genes. ROMA will assist in the discovery of genes and markers important in cancer, and the discovery of loci that may be important in inherited predispositions to disease.

Aneuploidy↗

PubMed2003

Microvascular function regulates intestinal crypt response to radiation.

Recent evidence suggests that microvascular endothelial apoptosis represents the primary lesion in radiation damage to the gastrointestinal (GI) tract. Rescue of endothelium by depletion of acid sphingomyelinase or i.v. treatment with basic fibroblast growth factor (FGF) prevented the lethal GI syndrome in C(57)Bl/6 mice. Here we show that basic FGF increased crypt survival after irradiation by 2-3 fold, with a dose modification factor at D(10) of 1.15 (P < 0.01). Basic FGF inhibited initial crypt damage, assessed by crypt shrinkage at 18-24 h, but did not significantly affect the regeneration of surviving crypts at 3.5 days after irradiation. These data suggest that microvascular function regulates expression of radiation-induced crypt stem cell clonogen damage in the evolution of radiation injury to the GI mucosa.

Animals↗

PubMed2003

Development of endometrial cancer after radiation treatment for cervical carcinoma.

OBJECTIVE: To detail the Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center experience with 23 patients treated with radiation therapy for invasive cervical carcinoma who subsequently developed endometrial carcinoma. METHODS: We conducted a retrospective chart and pathology review on patients diagnosed with endometrial cancer between 1976 and 2000 who had previously received definitive radiation treatment for cervical cancer. Abstracted data included patient demographics, type of radiation therapy, histological grade, histological subtype, and stage of endometrial cancer. RESULTS: The mean age at endometrial cancer diagnosis was 64.4 years (range 53-80), and the average latency period from initial therapy to development of endometrial carcinoma was 14 years (range 6-27). Distribution by stage, grade, and histology was as follows: stage I, five (22%); stage II, one (4%); stage III, nine (39%); stage IV, seven (30%); unknown stage, one (4%); grade 1, one (4%); grade 2, three (13%); grade 3, 17 (74%); unknown grade, two (9%); carcinosarcoma, eight (35%); endometrioid, four (17%); papillary serous, six (26%); clear cell, one (4%); mucinous, one (4%); undifferentiated, one (4%); and unknown histology, two (9%). The median survival was 24 months, and the 2- and 5-year survival rates were 50% (95% confidence interval [CI] 31.4%, 78.9%) and 21% (95% CI 8.1%, 56.3%), respectively. CONCLUSION: Patients treated with definitive radiation therapy for invasive cervical cancer may still have viable endometrium at risk for neoplasia. Endometrial cancers that develop after radiation treatment have a preponderance of high-risk histological subtypes and, consequently, a poor prognosis.

Adenocarcinoma↗

PubMed2003

Palliative surgery for bowel obstruction in recurrent ovarian cancer:an updated series.

OBJECTIVE: Intestinal obstruction is a frequent sequela of recurrent ovarian cancer. Previous series report median survivals of 3-6 months in patients undergoing surgery for obstruction due to recurrent disease. We analyze a contemporary series of patients to determine if outcomes have changed in patients undergoing palliative surgery. METHODS: We retrospectively reviewed all patients undergoing surgery for intestinal obstruction due to recurrent ovarian cancer from 1994 to 1999. RESULTS: During the study period, 68 operations were performed on 64 patients. Mean age at the time of obstruction was 57.3 years. Mean time from original diagnosis of ovarian cancer to obstruction was 2.8 years. Surgical correction (intestinal surgery performed for relief of obstruction) was attained in 57 of 68 (84%) cases. Successful palliation (the ability to tolerate a regular or low-residue diet at least 60 days postoperatively) was achieved in 71% of cases where surgical correction was possible. The rate of major surgical morbidity was 22%. There was one death from pulmonary embolus and one from peritonitis. Two other deaths occurred due to progression of disease, for an overall perioperative mortality rate of 6%. Postoperative chemotherapy was administered in 45 of 57 (79%) cases where surgical correction was possible. The median survival of the entire cohort was 8 months. If surgery resulted in successful palliation, median survival was 11.6 months, versus 3.9 months for all other patients (P <.01). CONCLUSIONS: The majority of our patients undergoing surgery had successful palliation, and were able to receive further chemotherapy. They were discharged home, and could tolerate solid food.

Adult↗

PubMed2003

The effects of CO2 pneumoperitoneum on the survival of women with persistent metastatic ovarian cancer.

OBJECTIVES: The effects of CO(2) pneumoperitoneum on the survival of women with metastatic ovarian cancer have not been documented. We sought to describe the survival of women with persistent stage III-IV ovarian cancer as documented by positive second-look laparoscopy or laparotomy and to see whether the laparoscopic approach with CO(2) pneumoperitoneum has a negative effect on overall survival. METHODS: We conducted a retrospective review of all patients with FIGO stage III-IV invasive epithelial ovarian cancer who were found to have persistent disease at second-look surgery. All patients underwent primary surgery followed by intravenous chemotherapy and were clinically without evidence of disease prior to second-look surgery. Second-look laparoscopy began to be utilized regularly in 1994. The selection of the second-look surgical approach depended on the surgeon's discretion. CO(2) pneumoperitoneum was utilized for all laparoscopic cases with the maximum intra-abdominal pressure maintained at 15 mm Hg. Patients received a variety of additional intravenous, intraperitoneal, or oral chemotherapy following positive second-look surgery. RESULTS: Between 6/1/91 and 6/30/02, 289 patients were found to have persistent ovarian/peritoneal cancer at second look. Second-look operations included 131 (45%) transperitoneal laparoscopies and 139 (48%) laparotomies. Nineteen (7%) patients underwent laparoscopy followed immediately by laparotomy. The mean age, stage distribution, histology, grade, and size of residual disease at second look did not differ between the two groups. The median overall survival for patients who underwent laparoscopy, 41.1 months (95% CI, 33.2-58.1), did not significantly differ from that of the laparotomy group, 38.8 months (95% CI, 31.9-44.2) (P = 0.742). CONCLUSIONS: Transperitoneal laparoscopy with CO(2) pneumoperitoneum does not appear to reduce the overall survival of women with persistent metastatic intra-abdominal carcinoma of ovarian/peritoneal origin. The overall survival appears to be independent of the second-look surgical approach.

Carbon Dioxide↗

PubMed2003

Platinum retreatment of platinum-resistant ovarian cancer after nonplatinum therapy.

OBJECTIVE: The objective was to determine the response rate to platinum retreatment of "platinum-resistant" ovarian cancer after intervening nonplatinum therapy. METHODS: We retrospectively identified 30 patients with platinum-resistant ovarian cancer who received nonplatinum chemotherapy for recurrent epithelial ovarian cancer prior to additional platinum therapy. All patients were treated between July 1, 1997, and June 30, 2001. Platinum resistance was defined as less than a partial response to platinum therapy or progression within 6 months of the last platinum therapy. RESULTS: Overall, 7 of 30 patients experienced an objective response to platinum therapy (partial response, 23%; complete response, 0%) based on CT scan (2/21) and/or CA-125 (5/9) criteria. The median time to progression for the group was 17 weeks (range, 4-59 weeks). Several predictive factors were identified. The interval since the last platinum treatment did not appear to be predictive in this group. Only 1 of 16 patients who did not have an objective response to the most recent platinum-based therapy responded to platinum rechallenge. Similarly, no patient who received more than three intervening nonplatinum treatments responded to additional platinum therapy (0/10). CONCLUSIONS: Our small retrospective series suggest that the platinum-resistant category is heterogenous and includes patients who may respond to retreatment with platinum-based agents. This group includes the patients with prior platinum responses and early progression. However, patients without an objective response to the last prior platinum therapy or more than three intervening treatments are unlikely to respond to subsequent platinum therapy.

Adult↗

PubMed2003

Total laparoscopic radical hysterectomy with pelvic lymphadenectomy using the argon-beam coagulator: pilot data and comparison to laparotomy.

OBJECTIVES: The aim of this study was to describe the feasibility and outcome of total laparoscopic radical hysterectomy with pelvic lymphadenectomy for stage I cervical cancer using the argon-beam coagulator. METHODS: A retrospective review was performed of patients with FIGO stage IA1-IB1 cervical cancer who underwent a total laparoscopic approach for definitive surgical treatment. Comparison was made to a cohort of 195 patients who were treated with laparotomy. RESULTS: Between 12/2000 and 12/2002, 19 patients were offered the laparoscopic approach. The procedure was completed laparoscopically in 17 patients (89.5%). Two patients, in the beginning of the study, underwent conversion to laparotomy, 1 due to parametrial bleeding and 1 due to pelvic adhesions and cystotomy. Mean age was 42.6 years (range, 30-69 years); mean body mass index was 23.1 (range, 18-30); FIGO stage included IA1 with LVI (2), IA2 (6), IB1 (11). Mean pelvic lymph node count was 25.5 (range, 15-39), and 1 patient (5.3%) had positive nodes. Mean estimated blood loss was 301 cc (range, 75-1500 cc) compared to 693 cc in the laparotomy group (P < 0.01), mean operating time was 371 min (range, 230-600 min) compared to 295 min in the laparotomy group (P < 0.01), and mean hospital stay was 4.5 days (range, 3-11 days) compared to 9.7 days in the laparotomy group (P < 0.01). There were no ureteral injuries or fistula formation. All patients remain clinically disease free at the time of this report. CONCLUSIONS: Total laparoscopic radical hysterectomy with pelvic lymphadenectomy for selected patients with stage I cervical cancer is feasible, safe, and associated with a low morbidity in the pilot phase. Estimated blood loss and postoperative hospitalization appear shorter than historical controls, at the cost of longer operating time. Oncologic outcome requires longer follow-up.

Adult↗

PubMed2003

Bcl-2 and bax expression in advanced non-small cell lung cancer: lack of correlation with chemotherapy response or survival in patients treated with docetaxel plus vinorelbine.

Surgical series of non-small cell lung cancer (NSCLC) pathologic samples have shown that the expression of the proteins bcl-2 and bax, which regulate cell death, may have prognostic implications. Laboratory data also suggests that these proteins may impact chemotherapy response. In order to determine the rate of bcl-2 and bax expression in advanced NSCLC and assess the impact on chemotherapy response and patient survival, we performed immunohistochemistry on biopsy samples from patients enrolled in a phase I/II trial of vinorelbine plus docetaxel. We chose to study the pathology of patients in this specific trial because both docetaxel and vinorelbine phosphorylate bcl-2 and we hypothesized that this mechanism may affect clinical outcome. The goal of this study was to determine the feasibility of this analysis, and to observe any differences in response rate or survival based on bcl-2 or bax staining results. Unstained slides from paraffin blocks were obtained for 31 patients (55%) on the phase I/II trial. The patient characteristics for this subgroup did not differ significantly from the entire cohort of patients on the trials. Bcl-2 staining was positive in 5/31 samples (16%, 95% CI 3-29%) and bax was positive in 19/28 samples (68%, 95% CI 51-85%). Bcl-2 and bax staining did not correlate with response (p = 0.65 and 1.00 respectively, Fisher's exact test), or survival (by Kaplan-Meier curves). In conclusion, bcl-2 and bax expression was similar in this population with advanced NSCLC to previously reported results for early stage disease, but did not predict response to vinorelbine plus docetaxel in this series.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Impact of intraoperative edema during transperineal permanent prostate brachytherapy on computer-optimized and preimplant planning techniques.

The purpose of this study was to prospectively evaluate intraoperative prostatic edema during prostate brachytherapy with real-time ultrasound imaging and assess its impact upon the postimplant dosimetry of computer-optimized intraoperatively planned patients. Fifty consecutive patients with early-stage favorable risk adenocarcinoma of the prostate underwent transperineal ultrasound-guided I125 brachytherapy. Ultrasound volume studies of the prostate were performed immediately before and after placement of brachytherapy needles in the operating room. Twenty-five patients underwent intraoperative computer-optimized treatment planning using a genetic algorithm. Twenty-five patients underwent preimplant ultrasound studies for preimplant treatment planning. Postimplant dosimetry was performed on computed tomography scans obtained after the implant. Statistical analysis was performed taking into account patient age, preneedle volume, increase in intraoperative edema, use of hormonal therapy, type of isotope, number of needles or seeds used, and seed activity. For the intraoperatively planned patients, a median increase of 30% in intraoperative volume was found for the entire group. No correlation between the extent of intraoperative edema and %D90 (percentage of prescribed dose that covers 90% of the target volume) was found. None of the other analyzed variables correlated with %D90. Patients whose treatment was planned preoperatively experienced a median increase of 18.4% in target volume. A negative correlation between the amount of edema and the %D90 was found to be statistically significant (-0.55, P = 0.0047). All patients who underwent prostate brachytherapy experienced intraoperative prostatic edema. When planned intraoperatively, the amount of edema had no impact on the %D90. This may be because of the ability of intraoperative computer-optimized treatment planning to account for edema related to the procedure. Preplanned patients who encountered a greater degree of intraoperative edema had less %D90 target coverage.

Aged↗

PubMed2003

10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer.

PURPOSE: 10-propargyl-10-deazaaminopterin (PDX) has superior antitumor efficacy in mouse xenograft models, likely attributable to increased uptake by the RFC-1 folate transporter and greater intracellular polyglutamylation. In a previous Phase I trial, stomatitis was the dose-limiting (and only clinically significant) toxicity of PDX. The recommended Phase II dose was 150 mg/m(2) i.v. every 2 weeks. Responses observed in patients with non-small cell lung cancer (NSCLC) in the Phase I trial prompted this Phase II trial. EXPERIMENTAL DESIGN: Patients had stage IIIB or IV NSCLC and either no previous chemotherapy or progression after initial response or stable disease to one previous chemotherapy regimen. Initially, PDX was administered at a dose of 150 mg/m(2) every 2 weeks. However, to decrease the frequency of stomatitis, the last 10 patients were treated at a dose of 135 mg/m(2). We planned to correlate PDX effects with folate and homocysteine levels and the expression of genes associated with folate transport and polyglutamylation. RESULTS: Thirty-nine patients were enrolled, 38 of whom were evaluable for response. Four patients had confirmed, major objective responses (10% based on intent to treat, 95% confidence interval 3-25) lasting 4, 9, 12, and 15 months. Twelve patients (31%) had stable disease. The median survival was 13.5 months. The predicted 1- and 2-year survival rates were 56 and 36%, respectively. Two patients (5%) suffered grade 4 stomatitis, and 6 (15%) had grade 3. No clinically significant myelosuppression occurred. No correlation between homocysteine or serum folate levels and severity of stomatitis was observed. Area under the curve (calculated using a limited sampling model) correlated with mucositis grade. A trend was noted between folate transporter expression and treatment effect. CONCLUSIONS: The broad applicability of this new antifolate with limited toxicity and proven efficacy in NSCLC encourage further development of this compound. Several trials are now underway combining PDX with other chemotherapeutic agents and testing its efficacy in other cancers.

Adult↗

PubMed2002

Is there a difference in outcome between stage I-II endometrial cancer of papillary serous/clear cell and endometrioid FIGO Grade 3 cancer?

PURPOSE: Several reports in the literature have shown that, compared with endometrioid adenocarcinoma, patients with papillary serous (PS) and clear cell (CC) histologic features do worse. However, it is unclear whether the outcome of PS/CC cancer is different from that of poorly differentiated endometrioid cancer. The purpose of this study was to compare the outcome between PS/CC and endometrioid International Federation of Gynecology and Obstetrics (FIGO) Grade 3 cancer and was limited to patients with Stage I-II uterine carcinoma. METHODS AND MATERIALS: Between November 1987 and September 1999, 83 patients with Stage I endometrial cancer and Stage II occult endometrial cancer were treated with simple hysterectomy and high-dose-rate intravaginal brachytherapy. Forty-one patients (49%) had FIGO Grade 3 endometrioid tumors (Group 1) and 42 (51%) had PS/CC histologic features (Group 2). The mean age was 63 years (range 30-89). Comprehensive surgical staging was done in 23 (28%) of 83 patients. Capillary space-like invasion (CSLI) was seen in 24 (29%) of 83 patients. The median dose of intravaginal brachytherapy when used alone was 21 Gy in 3 fractions. Additional external beam radiotherapy was given to 42 (51%) of 83 patients to 45 Gy. The two groups were balanced with regard to age, race, comprehensive surgical staging, amount of myometrial involvement, CSLI, lower uterine segment involvement, cervical involvement, and use of external beam radiotherapy. The median follow-up was 46 months (range 4-147). RESULTS: The pattern of relapse was as follows: vagina/pelvis in 5 of 14 patients, lungs in 8 of 15, intra-abdominal in 4 of 12, and supraclavicular lymph nodes in 1 of 14. One of the four intra-abdominal disseminations was in Group 1 and the other three in Group 2 (p = 0.6). The 5-year vaginal/pelvic control, disease-free survival (DFS), and overall survival (OS) rate was 93% (95% confidence interval [CI] 87-99%), 79% (95% CI 69-89%), and 74% (95% CI 64-85%), respectively. No significant difference in outcome was found between Groups 1 and 2. The 5-year vaginal/pelvic control rate was 97% (95% CI 91-100%) in Group 1 compared with 90% (95% CI 81-99%) in Group 2 (p = 0.2). The 5-year DFS rate was 79% (95% CI 64-95%) in Group 1 vs. 78% (95% CI 65-92%) in Group 2 (p = 0.6), and the 5-year OS rate was 71% (95% CI 55-87%) in Group 1 vs. 79% (95% CI 66-92%) in Group 2 (p = 0.3). The influence on outcome of age, race, comprehensive surgical staging, CSLI, amount of myometrial invasion, cervical involvement, lower uterine segment involvement, and presence of pure PS or CC histologic features was evaluated. On multivariate analysis, only CSLI correlated with poor DFS (p = 0.04; relative risk 3, 95% CI 1-9) and OS (p = 0.02; relative risk 3, 95% CI 1-6). CONCLUSION: On the basis of the results of this study, no significant difference in outcome exists between patients with Stage I-II endometrial cancer with PS/CC histologic features and those with similar stage disease, but with FIGO Grade 3 endometrioid histologic features. CSLI was the only independent predictor of poor DFS and OS.

Adult↗

PubMed2002

The significance of the amount of myometrial invasion in patients with Stage IB endometrial carcinoma.

BACKGROUND: The 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma defined Stage IB as disease with invasion of less than one-half of the myometrium, although most of the data on prognostic factors are based on invasion of the inner one-third, middle one-third, or outer one-third of the myometrium. The objective of this study was to determine whether the depth of myometrial invasion is correlated with outcome in patients with Stage IB endometrial carcinoma. METHODS: Between November, 1987 and June, 1998, 251 patients with Stage IB endometrioid adenocarcinoma of the uterus underwent simple hysterectomy followed by intravaginal brachytherapy. The depth of myometrial invasion was less than or equal to one-third (Group I) in 191 of 251 patients (79%) and greater than one-third to less than one-half (Group II) in 52 of 251 patients (21%). Comprehensive surgical staging (CSS) was done in 12% of patients. The two groups were balanced with regard to age (< 60 years vs. > or = 60 years), FIGO grade, lower uterine segment involvement (LUSI), CSS, and the use of postoperative external-beam radiation. The rate of capillary-like space invasion (CLSI), however, was 9% in Group I compared with 25% in Group II (P = 0.002). The median follow-up was 58 months. RESULTS: The overall 5-year actuarial local-regional control (LRC), disease free (DFS) survival, and overall survival (OS) rates were 95%, 92%, and 92%, respectively. These end points, however, did not vary significantly between the two groups. The 5-year LRC, DFS, and OS rates in Groups I and II were 96% versus 95%, respectively (P = 0.9); 92% versus 94%, respectively (P = 0.7); and 92% versus 90%, respectively (P = 0.5). On multivariate analysis, the influence on outcome of age, grade, amount of myometrial invasion, LUSI, and CLSI was evaluated. Only age > or = 60 years and FIGO Grade 3 were correlated with poor DFS (P = 0.02 and P = 0.03, respectively) and OS (P = 0.001 and P = 0.01, respectively). CONCLUSIONS: Based on this study, in patients with Stage IB endometrial carcinoma, the amount of myometrial invasion, defined as invasion less than or equal to one-third of the myometrium versus invasion greater than one-third and less than one-half of the myometrium, did not appear to influence outcome. Age > or = 60 years and FIGO Grade 3, however, emerged as independent prognostic factors for poor DFS and OS.

Adenocarcinoma↗