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Biomedical subjects

B Vikram

Publications and source records attributed to B Vikram.

At least 19 recordsLinked to original sources
PubMed1999

Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer.

An ineffective tumor-specific immune response from inadequate/incompetent antigen presentation could contribute to the failure in tumor control and its dissemination. Dendritic cells (DCs) have been shown to present antigen from apoptotic cells. We hypothesized that Flt3-ligand (Flt3L) therapy, which expands DCs in vivo, in combination with local tumor radiotherapy (RT), should improve antigen presentation from dying, irradiated tumor cells. RT + Flt3L reduced pulmonary metastases in a murine model of Lewis lung carcinoma and significantly improved survival in C57Bl/6 mice with established footpad tumors. Mice treated with Flt3L alone showed delayed tumor growth but eventually succumbed to tumor progression. The combination therapy of RT + Flt3L failed to impact survival in immunodeficient athymic mice, implicating the role of T cells in prolonging survival. These results support an attractive strategy of sequential RT and immunotherapy with Flt3L to enhance tumor antigen presentation, which may produce therapeutic responses against disseminated cancer and improvement in survival.

Animals↗
PubMed1999

Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation.

Hepatic tumors often recur in the liver after surgical resection. Postoperative radiotherapy (RT) could improve survival, but curative RT may induce delayed life-threatening radiation-induced liver damage. Because RT inhibits liver regeneration, we hypothesized that unirradiated, transplanted hepatocytes would proliferate preferentially in a partially resected and irradiated liver, providing metabolic support. We subjected F344 rats to hepatic RT and partial hepatectomy with/without a single intrasplenic, syngeneic hepatocyte transplantation. Hepatocyte transplantation ameliorated radiation-induced liver damage and improved survival of rats receiving RT after partial hepatectomy. We further demonstrated that transplanted hepatocytes extensively repopulate and function in a heavily irradiated rat liver.

Animals↗
PubMed1999

The relationship between dose heterogeneity ("hot" spots) and complications following high-dose rate brachytherapy.

PURPOSE: It is generally believed that "hot" spots should be avoided in radiotherapy because they lead to complications. Dose homogeneity within the target volume is much more difficult to achieve during brachytherapy than during external beam irradiation, and implants are rarely geometrically perfect. To not underdose some parts of the target volume, therefore, it may be necessary to accept hot spots in other parts of the target volumes, but it is not at all clear from the literature how much dose heterogeneity should be considered excessive. We undertook this study in an effort to determine just how high a dose to a hot spot is associated with clinically significant complications. METHODS AND MATERIALS: We studied 40 patients treated by high-dose rate brachytherapy with or without external irradiation. For each patient, we calculated the minimum dose to the "hottest" 1 cubic centimeter (cc) volume (Dmax1) and, for 18 patients, the minimum dose to the hottest 10 cc volume (Dmax10) as well. RESULTS: Considerable dose heterogeneity existed within the target volume. The Dmax1 ranged from 150-2000% (median 320%) of the minimum target dose (MTD). The median MTD/fraction was 2.50 Gy (range 1.50-25.00), and the median Dmax1/fraction was 10.00 Gy (range 3.75-150.00). The median Dmax1 from the entire course of brachytherapy was 75.00 Gy (range 25.00-550.00). Adding the doses from planned external irradiation, plus any prior irradiation to the same area, the median total Dmax1 was 112.50 Gy (range 30.00-580.00), yet the incidence of complications, even among those in the highest quartile of this dose range, was not greater than the lowest quartile. The total median Dmax10 was 85.00 Gy (range 32.00-130.00), but the incidence of complications was, again, similar whether the dose was in the lower or the upper half of this range (32.00-85.00 Gy, or 86.00-130.00 Gy, respectively). CONCLUSIONS: We had expected to find that the patients with the highest Dmax1 and/or Dmax10 would be the ones most likely to suffer complications, but the results did not support this hypothesis. Thus, dose heterogeneity, within the scope of our study, turned out to be rather unimportant with regard to complications. This finding contradicts the conventional wisdom and suggests that concerns about hot spots need not preclude optimization to ensure adequate dosage to all parts of the target volume.

Adult↗
PubMed1999

Brachytherapy in cancer of the head and neck.

This article provides a review of the general principles of brachytherapy for tumors in the head and neck. The different radionuclides used for this technique are discussed, as are the different capacities in which brachytherapy can be used, such as intraoperatively, as an adjuvant to surgery, to control nasopharyngeal carcinoma, following chemoradiotherapy, and for management of recurrent cancers.

Brachytherapy↗
PubMed1999

Experience-based demand scheduling: a more efficient model for radiation oncology.

The supply of radiation therapists has increased, whereas reimbursements have decreased. One hypothesis is that if we choose to employ as permanent staff sufficient therapists to handle the low-volume periods and scheduled temporary staff as the demand for radiation therapy services warrants, we would increase efficiency. Using current economic assumptions and the treatments delivered during the past 12 months, we analyzed the labor expense and revenue consequences of both full staffing and a lower level of staffing with per diem supplementation based on the scheduled patient load. We then correlated the scheduled treatments with the actual treatments delivered and finally, reexamined both the full-staffing model and the per diem supplementation model based on the predictions of our scheduling model. The reduction in full-time therapists and per diem supplementation did not produce substantial incremental revenue. However, examining the relationship between patients scheduled for treatment on the next day and patients actually treated, revealed an 11% "no show" rate with a 95% confidence interval of 1%. Our new, experienced-based model demonstrated considerable revenues to be realized by using the no-show factor to better use therapists by more aggressive scheduling of outpatients, therapists, and more flexible transportation of inpatients. We conclude that the experience-based model predicts the marginal revenue, but is silent on the quality of the medical care provided.

Appointments and Schedules↗
PubMed1999

Breast cancer screening in underserved women in the Bronx.

This article reports the results of mammography screening among socioeconomically disadvantaged women in Bronx, NY using a federally funded low-cost or no-cost cancer screening service. The New York State Department of Health provided funds for the uninsured through the Bronx Breast Health Partnership. All women < or = 40 years underwent screening mammography using both a mobile van unit and hospital-based mammographic x-ray unit, both American College of Radiology (ACR) accredited. Return visits were coordinated by a follow-up clinic at Montefiore Medical Center using a patient navigator who acted as an advocate for patients with abnormal screening findings. The overall detection rate of 12.9 per 1000 women screened was significantly higher than the New York State detection rate of 6 per 1000 and 5.1 per 1000 nationally. Availability of a patient navigator was an essential factor in the effectiveness of the work-up of problem cases. Low-cost or no-cost breast cancer screening programs can improve the availability, accessibility, acceptability, and utilization of mammography among underserved and uninsured women who are least likely to be screened otherwise.

Adult↗
PubMed1998

Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: a secondary analysis of RTOG 85-27.

PURPOSE: The purpose of the present study is to investigate the strength of association between anemia and overall survival, locoregional failure, and late radiation therapy (RT) complications in a large prospective study of patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer. METHODS AND MATERIALS: Between March 1988 and September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered into a randomized trial examining the addition of etanidazole (SR 2508) to conventional radiation therapy (RT) (66-74 Gy in 33-37 fractions, 5 days a week). Patients with hemoglobin (Hgb) levels measured and recorded prior to the second week of RT were included in this secondary analysis. Hemoglobin levels were stratified as normal (> or = 14.5 gm% for men, > or = 13 gm% for women) or anemic (< 14.5 gm% for men, < 13 gm% for women). Locoregional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of overall survival, locoregional failure, and late complications were tested by the Cox proportional hazard model. RESULTS: Of 504 eligible patients, 451 had a Hgb level measured and recorded prior to the second week of RT. One hundred sixty-two patients (35.9%) were considered to have a normal Hgb level and 289 patients (64.1%) were considered to be anemic. The estimated survival rate is 35.7% at 5 years in patients with a normal Hgb, versus 21.7% in anemic patients (p = 0.0016). The estimated locoregional failure rate is 51.6% at 5 years in patients with a normal Hgb, versus 67.8% in anemic patients (p = 0.00028). The estimated rate of grade 3 or greater toxicity is 19.8% at 5 years in patients with a normal Hgb, versus 12.7% in anemic patients (p = 0.063). On multivariate analysis, several variables were found to be independent predictors of survival including: T stage, Karnofsky performance status, N stage, age, total radiation dose to the primary, and Hgb level. Independent predictors of locoregional control included T stage, Karnofsky performance status, N stage, radiation dose, and Hgb level. The only variables which predicted for the development of late RT complications were gender (p = 0.0109) and age (p = 0.0167). These findings were consistent regardless of whether Hgb level was considered a dichotomous or continuous variable. CONCLUSION: Low Hgb levels are associated with a statistically significant reduction in survival and an increase in locoregional failure in this large prospective study of patients with advanced head and neck cancer. Hgb level should be considered as a stratification variable in subsequent studies of head and neck cancer. Strategies to increase Hgb prior to RT in patients with head and neck cancer may lead to improved survival and loco-regional control.

Analysis of Variance↗
PubMed1998

Rapidly alternating chemotherapy and radiotherapy instead of cystectomy for the treatment of muscle-invasive carcinoma of the urinary bladder: long term results of a pilot study.

BACKGROUND: The authors studied rapidly alternating chemotherapy and radiotherapy as the initial treatment for patients with muscle-invasive transitional cell carcinomas of the urinary bladder whose advanced age and lack of strength precluded cystectomy. METHODS: Twenty-one patients with T2 (28%) or T3 (72%) NXM0 carcinomas were treated by transurethral resection followed by chemoradiotherapy. Their median age was 73 years. The chemotherapy (consisting of methotrexate, vinblastine, doxorubicin, and cisplatin) was given during Weeks 1, 4 and 7. Radiotherapy (1.8-2 Gray [Gy] twice a day, to a total dose of 18-20 Gy per week) was given during Weeks 2, 5 and 8, for a final dose of 40 Gy to the pelvis plus 14-20 Gy boost to the affected bladder. RESULTS: There was 1 treatment-related death (5% of patients), but otherwise the acute toxicity was relatively mild. Cystoscopy 1 month after chemoradiotherapy did not reveal invasive cancer in any patient. Subsequent cystoscopies detected recurrent invasive cancer in 3 patients after 30, 44, and 82 months, respectively. The observed survival rate after 5 years was 37%, the cause specific survival rate was 63%, the metastasis free rate was 71%, and the local control rate was 80%. Eighty-four percent of patients had normal bladder function. CONCLUSIONS: Transurethral resection plus chemoradiotherapy was successful in preserving bladder function in the majority of the patients. The survival and progression free rates compared favorably with what has been reported recently after radical cystectomy and chemotherapy, and they add to the growing body of evidence that chemoradiotherapy might be a safe, effective alternative to cystectomy for many patients with muscle-invasive carcinoma of the urinary bladder.

Aged↗
PubMed1998

Close or positive margins after surgical resection for the head and neck cancer patient: the addition of brachytherapy improves local control.

PURPOSE: Microscopically positive or close margins after surgical resection results in an approximately 21-26% local failure rate despite excellent postoperative external radiation therapy. We sought to demonstrate improved local control in head and neck cancer patients who had a resection with curative intent, and had unexpected, microscopically positive or close surgical margins. METHODS AND MATERIALS: Twenty-nine patients with microscopically close or positive margins after curative surgery were given definitive, adjuvant external radiation therapy and 125I brachytherapy. All 29 patients had squamous cell cancer and tonsil was the most common subsite within the head and neck region. After external radiation therapy and thorough discussions with the attending surgeon and pathologists, the slides, gross specimens, and appropriate radiographs were reviewed and a target volume was determined. The target volume was the region of the margin in question and varied in size based on the surgery and pathologic results. Once the target volume was identified the patient was taken back to the operating room for insertion of 125I seeds. Activity implanted (range 2.9-21.5 millicuries) was designed to administer a cumulative lifetime dose of 120-160 Gy. RESULTS: Twenty-nine patients were followed for a median of 26 months (range 5-86 months). Two-year actuarial local control was 92%. CONCLUSION: 125I, after external radiation therapy, is an excellent method to improve local control in the subset of patients with unexpectedly unsatisfactory margins.

Brachytherapy↗