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Biomedical subjects

R Weichselbaum

Publications and source records attributed to R Weichselbaum.

At least 91 records · Page 5Linked to original sources
PubMed1983

An in vitro investigation of x-ray sensitivity in fibroblasts from patients with retinoblastoma.

In vitro x-ray survival experiments were performed on fibroblast strains derived from nine patients with sporadic unilateral retinoblastoma, 26 patients with hereditary retinoblastoma, and six normal controls. The x-ray sensitivity of the strains derived from the sporadic retinoblastoma patients and normal controls did not significantly differ from one another. The fibroblast strains derived from patients with hereditary retinoblastoma were significantly more radiosensitive to killing by x-rays as measured by clonogenic survival than either the sporadic strains or the strains derived from normal controls. We hypothesize that the increased in vitro radiosensitivity observed in some hereditary retinoblastoma strains is a reflection of an as yet uncharacterized defect in DNA or DNA replication postirradiation.

Cell Survival↗
PubMed1981

Speech and survival: tradeoffs between quality and quantity of life in laryngeal cancer.

In State T3 carcinoma of the larynx (carcinoma restricted to the vocal cords, causing complete immobility of the cords but not extending to adjacent structures), laryngectomy leads to a three-year survival rate of approximately 60 per cent and the loss of normal speech. Radiation therapy, on the other hand, leads to a lower survival (30 to 40 per cent at three years) but preserves normal or nearly normal speech. We investigated attitudes toward the quantity and quality of life in 37 healthy volunteers, interviewing 12 firefighters and 25 middle and upper management executives to determine their preferences for longevity and voice preservation. We used the principles of expected utility theory to develop a method for sharpening decisions involving tradeoffs between quantity and quality of life. Our analysis indicates that to maintain their voices, approximately 20 per cent of volunteers would choose radiation instead of surgery. These results suggest that treatment choices should be made on the basis of patients' attitudes toward the quality as well as the quantity of survival.

Attitude↗
PubMed1981

The characteristics of long-term survivors of lung cancer treated with radiation.

Between 1968 and 1974, 348 patients with lung cancer were primarily treated with radiation therapy. There were 66 such patients (19%) who survived a minimum of 18 months and are the subject of this report. Of this group, 30 patients have no evidence of disease from 18-96 months, with a median follow-up of 38 months. Thirty-three patients are dead of disease. The five-year actuarial survival of the total group of 348 patients was 5.6%. There were 14 stage I and II patients who survived a minimum of 18 months, of whom 11 had no evidence of disease. Of the 42 Stage III patients, 18 presently show no evidence of disease. There were 13 patients who failed with locally recurrent disease; in this group a dose-response relationship was demonstrated. A local failure rate of 50% (4/8) was observed for patients who received fewer than 5000 rad, 22% (6/27) for patients receiving 5000-5500 rad, 18% (2/11) in patients receiving 5500-5900 rad, and 5% (1/20) for patients who received more than 5900 rad. Radiotherapeutic technique was a significant variable in local failure. Forty-six percent (6/13) of those patient failures may have been eliminated with the use of careful treatment planning with simulation. A statistically significant difference in dose was noted for patients with central recurrence, mean dose 4725 rad, 1561 RET, 81 TDF, when compared with patients with control of gross disease with radiation, mean dose 5740, 1880 RET, 108 TDF. There were four patients with marked early complications (6%) and eight patients with late complications (12%). There were no deaths attributable to radiation. Although most patients with advanced lung carcinoma die of distant disease, a significant number of patients can achieve long-term survival when radically treated with high-dose radiation therapy.

Actuarial Analysis↗
PubMed1981

Increased therapeutic index using moderate dose methotrexate and leucovorin twice weekly vs. weekly high dose methotrexate-leucovorin in patients with advanced squamous carcinoma of the head and neck: a safe new effective regimen.

A new intensive methotrexate regimen for the treatment of advanced squamous carcinoma of the head and neck is presented, employing twice-weekly parenteral low-moderate doses of methotrexate and a single parenteral dose of leucovorin 24 hours following methotrexate. Toxicity and therapeutic results in 20 patients treated with this regimen favorably with results of weekly high-dose methotrexate-leucovorin in 36 patients treated immediately before initiation of the new regimen. Moderate nephrotoxicity and mild gastrointestinal/mucosal toxicity were common to both, while myelotoxicity was rarely seen with the low dose regimen and was more frequent with the high-dose regimen. Partial response was observed in 60% of patients treated on the intensive low-moderate dose schedule, and 50% of patients previously untreated with methotrexate on the weekly high-dose schedule. None of 12 patients previously failing low-moderate doses of methotrexate responded to high doses administered in this trial. The characteristics of antitumor response with low-moderate and high-dose schedules were similar except for the median dose required to attain response (50 mg/m2 vs. 3 g/m2) and the lesser toxicity of intensive lower dose therapy with leucovorin.

Adult↗
PubMed1981

Chemotherapy for advanced carcinoma of the head and neck. A clinical update.

Optimal therapy for stage III and stage IV squamous carcinoma arising in the head and neck requires a multidisciplinary approach, including chemotherapy. Advances have identified several chemotherapeutic agents and combinations of agents that show substantial antitumor activity in this disease. While antitumor activity can be documented, experience indicates the duration of antitumor effect is short, and the toxicity may limit further therapy. To date, studies have not shown an advantage of combination chemotherapy over single agents. Theoretically, combination chemotherapy should increase patient survival through regression of the primary tumor as well as ablation of distant metastases. An analysis of recent trials with patients who received induction chemotherapy before definitive local treatment suggests that regression of tumor in stage III and stage IV lesions before definitive therapy may increase local treatment for regional disease. Randomized trials are needed to confirm or disprove the efficacy of combination chemotherapy for advanced squamous carcinoma of the head and neck.

Carcinoma, Squamous Cell↗
PubMed1981

Twice-a-day fractionation preoperative radiotherapy in patients with carcinoma of the bladder: preliminary report.

There were 13 patients with carcinoma of the bladder who received preoperative radiotherapy by a modified regimen before cystectomy. Doses of 135 rad were delivered twice daily for 10 days (2,700 rad) to a 15 times 15 cm. portal and followed by immediate cystectomy. Patient tolerance has been excellent, morbidity has been minimal and no increase in operative time, blood loss of major intraoperative or postoperative complications has ensued. The theoretical and practical advantages of this regimen may outweight either the standard regimen of 4,500 rad with a 4-week hiatus before operation or the high dose, short course regimen of 2,000 rad in 5 days and immediate cystectomy.

Adult↗
PubMed1981

The differential diagnosis of the mass in the neck. A fresh look.

A diagnosis of undifferentiated carcinoma by light microscopy in a neck node biopsy is insufficient to come to a conclusive answer as to the type of tumor with which one is dealing. The fact that undifferentiated carcinoma by light microscopy may very well be a histiocytic lymphoma with a different mode of treatment and an increasingly improved cure rate has changed the mode of evaluation in arriving at a diagnosis of the node in the neck with no visible primary in the upper aerodigestive tract.

Biopsy, Needle↗
PubMed1980

Limited penetration of methotrexate into human osteosarcoma spheroids as a proposed model for solid tumor resistance to adjuvant chemotherapy.

It is generally accepted that oxygen has a limited ability to diffuse into solid tumor masses. However, the question of the ability of chemotherapy agents to penetrate solid tumor masses has not been evaluated. This clearly would have an impact on the ability of chemotherapy to control microscopic disease during the "avascular" phase of growth. An attempt was made to evaluate the ability of methotrexate to penetrate solid tumor masses when grown in three dimensions (spheroids). Since methotrexate is used in the clinical management of human osteosarcoma, we chose this drug-tumor combination for our studies. This was done by growing human osteosarcoma cells into spheroids and exposing spheroids of various sizes to tritiated methotrexate. Audioradiographs were obtained from sections through the center of spheroids of various sizes. Our findings suggest that methotrexate has a limited ability to penetrate into avascular tumor masses when grown in three dimensions. This is most evident when the tumor masses are approximately 250 micron and larger in diameter. In addition, we compared the degree of penetration of methotrexate to the growth fraction of the tumor, as measured by tritiated thymidine, and found that the growth fraction was much greater than the fraction of cells reached by methotrexate. We conclude that the limited ability of methotrexate to penetrate solid tumor masses offers an alternative explanation for the limited effectiveness of methotrexate when used as an adjuvant for osteosarcoma. We question whether the established biochemical mechanisms for methotrexate resistance are comprehensive explanations for its limited clinical effectiveness.

Autoradiography↗
PubMed1979

Predefinitive and postdefinitive chemotherapy for locally advanced squamous carcinoma of the head and neck.

Advanced squamous carcinoma of the head and neck remains refractory to the best combinations of surgery and radiotherapy. Weekly methotrexate in high doses with leucovorin "rescue" is able to produce significant remissions in a majority of patients treated palliatively for recurrent disease yet is associated with little or no toxicity. We have attempted to improve the cure of patients with advanced disease by the use of high dose methotrexate (3-7.5 g/M2) and leucovorin prior to and following definitive surgery and/or radiotherapy. In a series of 24 patients we have achieved a response rate of 52%, with minimal toxicity during chemotherapy, and no apparent potentiation of toxicity with radiotherapy. Survival free of disease appears to be prolonged in patients with response to this chemotherapy. Multimodality approaches to locally advanced squamous carcinoma of the head and neck may soon yield improved cure rates.

Carcinoma, Squamous Cell↗
PubMed1978

Fallacy of the five-year survival in lung cancer.

Patients with lung cancer can be treated by either surgical extirpation or radiation. The former may offer increased five-year survival and prolonged life expectancies as compared to the latter, but subjects patients to the immediate risk of thoracotomy. We interviewed patients with "operable" lung cancer and found that they were quite averse to taking risks involving the possibility of immediate death. When these data about patients' attitudes were combined with data about survival after both radiation therapy and operation, it appeared that radiotherapy would be the preferred therapeutic plan for several of these patients. These results emphasize the importance of choosing therapies not only on the basis of objective measures of survival but also on the basis of patient attitudes.

Age Factors↗
PubMed1978

Palliation of hepatic metastasis.

Between 1971 and 1975, 55 patients underwent palliative radiation therapy for symptomatic hepatic metastasis. Most patients received 2400 rad in 300 rad fractions to the entire liver. There were 31 patients who received concomitant chemotherapy, and 14 who were prior chemotherapy failures. Ninety percent of the patients with symptomatic pain and liver enlargement and significant palliation of their symptoms. The median survival of the entire group was 4.5 months, while those patients experiencing an excellent response (21) had a median survival of 9 months. The median survival of patients having an excellent response to radiation is comparable to that of patients having regional arterial chemotherapy while incuring fewer complications. The overall complication rate of those patients completing therapy (50) was 12%.

Female↗
PubMed1978

An aggressive approach to marginally resectable lung cancer.

Between July 1968 and December 1974, 53 patients with lung cancer were planned for preoperative irradiation and surgery. All patients were considered clinically marginally resectable because of advanced local disease, 4 Stage II patients, with limited pulmonary reserve and 49 Stage III patients. Most patients received 3000 to 4000 rad followed in two weeks by thoracotomy. Forty-six patients were explored and 38 were resectable. Twelve patients are alive with a median follow-up of 48 months. The cumulative 5-year survival of all resectable patients is 27%. The survival of patients with marginally resectable lung cancer treated by accelerated radiotherapy followed by aggressive surgery approaches the survival experience of patients with primary resectable lung cancer and is superior to such patients treated with radiation therapy alone.

Bronchial Fistula↗
PubMed1978

The role of radiation therapy in the treatment of soft tissue sarcomas of childhood.

The treatment of soft tissue sarcomas in children at the Joint Center for Radiation Therapy, Children's Hospital Medical Center, and the Sidney Farber Cancer Institute from 1970 to 1976 has been reviewed. Twenty-seven patients were diagnosed with rhabdomyosarcoma, and twenty patients were diagnosed with soft tissue sarcomas of other histologies. An aggressive, combined modality therapeutic approach was applied in the treatment of all patients with emphasis placed on conservation of function. Of irradiated patients, local control was achieved in 96% of those with rhabdomyosarcoma and 85% in other sarcomas. Cumulative relapse-free survival (actuarial) at 5 years is projected at 65% for the rhabdomyosarcoma patients and at 63% for the other sarcoma patients. Although there were differences in chemotherapy regimens (vincristine, actinomycin-D and cyclophosphamide for rhabdomyosarcoma and adriamycin and DTIC for other soft tissue sarcomas), the surgical and radiation therapeutic approaches are similar for both groups. The high probability of local control using function-conserving surgery and high dose radiation therapy supports this emerging approach. Improvements in survival will require better control of metastatic disease.

Adolescent↗
PubMed1978

Initial adjuvant therapy in advanced squamous cell carcinoma of the head and neck employing weekly high dose methotrexate with leucovorin rescue.

Our initial experience with weekly high dose methotrexate with leucovorin rescue (MTX-LCV), in advanced recurrent or metastatic squamous cell carcinoma of the head and neck with a 77% tumor response rate and high therapeutic index, prompted a trial of MTX-LCV as initial adjuvant therapy in high risk nonmetastatic patients. Results in 11 patients are presented and confirm the high response rate to MTX-LCV and the low incidence of myelotoxicity and mucositis, when concurrent urinary alkalinization is employed. Initial MTX-LCV administrations has not compromised subsequent optimum aggressive combinations of surgery and radiation therapy. Cytoreduction with MTX-LCV may be safely used initially in combined therapy for high risk squamous cell carcinoma of the head and neck.

Carcinoma, Squamous Cell↗