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Biomedical subjects

L B Marks

Publications and source records attributed to L B Marks.

106 records · Page 6Linked to original sources
PubMed1992

Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B.

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).

Adenocarcinoma↗
PubMed1992

Radiotherapy for prostate cancer: should the seminal vesicles be considered target?

During radiotherapy for prostate cancer, the ability to predict occult seminal vesicle invasion is important since irradiation of the entire seminal vesicles necessitates enlarging the radiation fields beyond what is usually used to irradiate the prostate gland alone. We analyzed the records of 302 patients with clinical Stage T1 or T2 adenocarcinoma of the prostate treated with radical surgery at Duke University Medical Center between 1970 and 1983. Univariate and multivariate analyses were used to examine the relationship between the risk of occult seminal vesicle involvement (defined herein as histologic involvement of the seminal vesicles not detected by physical or radiologic examination) and the following factors: histologic grade, age, clinical stage, and preoperative acid phosphatase. Among 249 patients with complete information, increasing histologic grade (p < 0.001) and clinical stage (p < 0.04) were found to be the strongest predictors of occult seminal vesicle invasion. Conversely, seminal vesicle invasion was very unusual in well-differentiated T1-T2 tumors (6%). This low risk group represented 28% (70/249) of this patient population. There appears to be a substantial subset of patients with well differentiated T1 or T2 tumors who are at very low risk for occult seminal vesicle involvement and in whom the seminal vesicles can be excluded from the target volume. The reduction in target volume may reduce normal tissue reactions, facilitate dose escalation, and possibly increase local control rates.

Adenocarcinoma↗
PubMed1992

The role of radiotherapy in patients with advanced seminomatous germ cell tumors. Controversies in management. Part 2.

The role of radiotherapy in the management of advanced seminomatous germ cell tumors remains controversial. The authors review the available literature, and recommend radiotherapy for stage II seminoma with bulky abdominal metastases (greater than 10 cm) under the following circumstances: As primary therapy only if the patient cannot or will not be treated with chemotherapy; as an adjuvant following chemotherapy in patients with residual masses of any size. Similar recommendations are made regarding the role of radiotherapy in the management of extragonadal seminoma outside the central nervous system.

Dysgerminoma↗
PubMed1992

Radiation therapy for testicular seminoma: controversies in the management of early-stage disease.

Subdiaphragmatic irradiation remains the standard treatment for patients with stage I and IIA testicular seminoma. Elective mediastinal irradiation is not indicated. In well-selected patients with stage I disease, aggressive surveillance may be a reasonable alternative to elective irradiation. We believe that bipedal lymphangiography is useful in staging, radiation field design, and follow-up. Other controversies in the radiotherapeutic management include the optimal radiation dose and appropriate target volume.

Dysgerminoma↗
PubMed1991

Accelerated repopulation: friend or foe? Exploiting changes in tumor growth characteristics to improve the "efficiency" of radiotherapy.

Accelerated repopulation (rapid multiplication of surviving clonogens) during a course of radiation therapy may contribute to local failure. This possibility has prompted accelerated treatment programs in an attempt to reduce overall treatment time, thereby minimizing the impact of repopulation. However, accelerated dose delivery at the start of treatment may not be advantageous since many of the tumor cells are likely to be hypoxic (non-cycling cells) and therefore relatively radioresistant. Conversely, accelerated treatment is likely to be most helpful later in treatment when the tumor has shrunk and accelerated repopulation of clonogens is a dominant factor. A series of calculations are presented that stimulate changes in tumor size, clonogen number, clonogen repopulation, and growth fraction during a course of fractionated radiation treatments for an idealized 2 cm diameter spherical tumor. The efficiency of each fraction of radiation is calculated for different radiation fractionation schemes. Efficiency is defined as the change in Log clonogen number (reflecting cell death due to radiation minus repopulation that has occurred during the interval between fractions) per Gy. These calculations suggest that relatively low total daily doses (approximately 2 Gy) are most efficient early in treatment. Higher daily doses are less efficient since the growth fraction is relatively low at the start of treatment. Later in treatment, as the tumor shrinks and the growth fraction approaches 1, accelerated repopulation becomes a major problem and higher total daily doses are more efficient. At this point, accelerated hyperfractionation should be used to increase the daily dose without exposing normal tissues to high fraction sizes. Thus, changes in tumor growth characteristics are exploited and dose delivery can be optimized by escalating daily irradiation doses during a course of fractionated irradiation. Strict interpretation of these conclusions must be tempered by the various assumptions and uncertainties included in this model. The concept of efficiency is useful since it reflects the competing effects of clonogen repopulation and radiation induced clonogen sterilization.

Cell Division↗
PubMed1991

Role of lymphangiography in staging testicular seminoma.

Bipedal lymphangiography (LAG) and abdominal/pelvic computerized tomography (CT) are both useful in evaluating retroperitoneal lymph nodes in early-stage testicular seminoma. Fifty-four patients who had both radiologic studies performed between 1982 and 1986 were identified, and their films were reviewed. Four patients had evidence of retroperitoneal lymph node metastases on both CT and LAG. Of the 50 patients who had normal findings on CT scan, 39 (78%) had a normal LAG and 11 (22%) had a positive LAG. All 11 patients had architectural abnormalities within normal-sized nodes. No patient had positive findings on CT with negative LAG. In addition to aiding in staging, LAG is very useful in designing radiation treatment portals. Therefore, we believe that LAG can continue to play an important role in the accurate staging and treatment of patients with testicular seminoma.

Dysgerminoma↗
PubMed1991

The influence of volume on the tolerance of the brain to radiosurgery.

Radiosurgery (delivery of a high dose of radiation to a small volume of the brain) is usually well tolerated since the volume of brain irradiated is small. Despite growing interest in radiosurgery, the influence of the volume of brain irradiated on the tolerance of the brain to radiation is not well understood. The results of six studies reporting clinically significant radiation reactions following radiosurgery for arteriovenous malformations are reviewed. In the combined series, 23 (9%) of 255 patients developed a clinically significant radiation reaction. The volume of brain irradiated and the dose delivered in each of these 23 patients are presented. The compiled data suggest that the previously presented guidelines may underestimate the risks of radiosurgery. Additional clinical and experimental data are needed to determine "safe" doses of radiation to be used during radiosurgery.

Brain↗
PubMed1991

The role of radiation therapy in the treatment of testicular germ cell tumors.

Infradiaphragmatic radiotherapy remains the treatment of choice for patients with stage I and II (small volume) testicular seminoma. With this approach, the disease-free survival rate exceeds 90% to 95%, and the ultimate disease-free survival rate (including salvage) is 95% to 100%. Initial therapy for patients with large-volume stage II, III, and IV disease should include multiagent systemic chemotherapy. Involved field radiotherapy is recommended for these patients following the chemotherapy, especially in patients with residual masses larger than a few centimeters. Although not used frequently in the United States, infradiaphragmatic radiotherapy is a viable treatment option for patients with clinical stage I testicular nonseminomas. Such therapy results in approximately an 85% to 90% relapse-free survival rate, with an ultimate survival rate (including salvage) approaching 100%. Initial therapy for patients with stage II or greater disease generally should include chemotherapy and/or surgery. Radiotherapy is often useful as post-chemotherapy consolidation, especially for unresectable masses. For extra-gonadal seminomas, radiotherapy is useful as definitive therapy for small-volume disease and as consolidative therapy (postchemotherapy) for more advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A standard dose of radiation for "microscopic disease" is not appropriate.

Elective irradiation of sites of potential occult tumor spread is often part of a patient's radiation therapy program. The required radiation dose (D) depends on the probability that occult disease exists (P(occ)), the number of sites at risk (A), the number of tumor clonogens present (Ni), their radiation sensitivity, and the desired control rate. An exponential model of cell survival is used to quantify the importance of these factors. Control Probability = [1 - Pocc x (1 - e-Ni x (SF2)D/2)]A; SF2 = surviving fraction after 2 Gy. Implications for clinical radiation therapy include: 1. Since the number of clonogens in an occult site may vary from 10 degrees to 10(8), Ni is the major determinant of the required dose. The intrinsic radiation sensitivity of the clonogens (SF2) is also extremely important in determining the dose. Other factors are less influential since they vary less. 2. The variability of Ni (8 logs) is larger than the variation in cell number seen with gross disease (1 cm3 versus 1000 cm3, 3 logs). When Ni approximately 10(8), the required dose approaches that needed for small volume gross disease (10(9) cells, 1 cm3). 3. The dose prescribed to elective sites should reflect the risk of occult disease based on the primary tumor site, stage, and grade. 4. Regions where clinicoradiologic evaluation is difficult (e.g., pelvis and obese neck) require higher doses because macroscopic tumor deposits may exist. 5. Relatively low doses (10 to 30 Gy) are often thought to be inadequate for microscopic tumor. However, similar doses have been reported to sterilize microscopic tumor in ovarian, rectal, bladder, breast, and head and neck carcinomas. Relatively low doses should not be discounted since they may be useful in select cases when normal tissue tolerances and/or previous irradiation treatment limit the radiation dose.

Cell Survival↗
PubMed1990

Testicular seminoma: clinical and pathological features that may predict para-aortic lymph node metastases.

Patients with clinical stage I testicular seminoma usually receive elective para-aortic lymph node radiation after orchiectomy, which is effective in controlling subclinical microscopic disease. However, the majority of patients with clinical stage I seminoma do not harbor occult metastases and, therefore, do not require elective nodal treatment. Vascular space invasion by the primary testis tumor recently has been shown to be an important predictor of metastases in nonseminomatous tumors but no such information exists to date in pure seminoma. Therefore, patients with clinical stage I testicular seminoma were compared to clinical stage II to IV cancer patients with respect to the presence of several features of the primary tumor. Vascular space invasion was identified significantly less frequently in stage I cancer patients (17%, 5 of 29) than in those with stage II or greater disease (39%, 11 of 28, p equals 0.03, 1-tailed t test). Microscopic invasion of the tunica and rete testis, and necrosis also were identified slightly more frequently in the higher stage cancer patients. Of the 12 patients with a maximum tumor dimension of more than 6 cm. 9 (75%) were in the stage II or higher group. Patient age, symptom duration and presenting complaint were similar in the 2 groups. Many higher stage cancer patients did not exhibit aggressive histological characteristics and, therefore, the absence of these features cannot be used to select patients for surveillance. On the other hand, patients with clinical stage I tumors that exhibit vascular space invasion may have an increased rate of occult para-aortic lymph node metastases. Therefore, the presence of vascular space invasion may be a useful criterion for exclusion of patients from surveillance protocols. Confirmatory data are needed before a final recommendation can be made.

Adult↗
PubMed1989

Dermatofibrosarcoma protuberans treated with radiation therapy.

Dermatofibrosarcoma Protuberans is an uncommon soft tissue tumor that is locally aggressive, prone to recur locally following excision, and has a low propensity for metastasis. Ten patients have received radiation (both external beam and interstitial implant) as part of, or as their only treatment, at Massachusetts General Hospital from 1979-1987. Three patients received radiation alone (66.7-75 Gy) for gross palpable disease. One patient has slowly regressing nodules at 33 months; the other two had complete regression and are free of disease at 24 and 26 months posttreatment. Seven patients received radiation in conjunction with surgery. One received both preoperative and postoperative radiation and six received postoperative radiation (60-67 Gy) for microscopic residual disease following resection. Six of these seven patients are free of disease 16 to 105 months following treatment. One patient, with diffuse microscopic tumor infiltration of the scalp, had a local recurrence within the radiation field 16 months following 64.4 Gy. There has been no significant treatment related morbidity. Even though the present experience is limited and the follow-up brief, it does suggest that radiation can be considered a viable therapeutic option in the patient who has a lesion that is not resectable.

Adult↗
PubMed1988

Invasive bladder carcinoma: preliminary report of selective bladder conservation by transurethral surgery, upfront MCV (methotrexate, cisplatin, and vinblastine) chemotherapy and pelvic irradiation plus cisplatin.

Methotrexate, Cisplatin, and Vinblastine (MCV) was followed by Cisplatin plus radiation therapy in 19 patients with muscle-invading clinical Stage T2-4NXM0 transitional cell carcinoma of the urinary bladder (including cystectomy candidates), to achieve local control and prevent distant metastases. Radical cystectomy was recommended for all patients who failed to reach a complete response (CR = biopsy negative and cytology not positive) following MCV and Cisplatin X 2 plus 4000 cGy. Completely responding patients, and those partially responding patients unsuited for cystectomy, were selected for bladder conservation treated with additional irradiation to the bladder tumor volume (total 6,480 cGy) plus one additional Cisplatin treatment. Dose reductions were required for stomatitis in 26%, mild bone marrow depression in 58%, and renal toxicity in 5% of the patients. During the Cisplatin/4000 cGy, mild dysuria occurred in 68% of patients and 36% had mild bowel hyperactivity. Serious complications have occurred in two patients to date. One patient had recurrent pulmonary emboli, marked reduction in bladder capacity, and diarrhea. A second had bladder perforation during cystoscopic evaluation after MCV and a small bowel obstruction after Cisplatin and 4000 cGy. There was no treatment-related sepsis. Three patients had initial complete transurethral resection of their tumors and therefore 16 patients are evaluable for tumor responsiveness to this protocol. Four patients (25%) were biopsy negative and cytology negative, whereas three additional patients (19%) were biopsy negative but cytology positive following initial MCV. Six patients (38%) were biopsy negative and cytology negative whereas three additional patients (19%) were biopsy negative and cytology positive following MCV and Cisplatin X 2 plus 4000 cGy pelvic radiation. Of the entire group, 9 patients were treated with full-dose radiotherapy. All of these patients are alive without evidence of tumor on rebiopsy of the original tumor site, but one has a persistent positive cytology. Seven patients had a radical cystectomy and 6 are disease free. The treatment of 3 patients deviated from the protocol. Overall, only one patient has developed distant metastases and currently 84% of the patients are disease-free, although follow-up is short. To date, this feasibility study has been clinically practical and well tolerated. The proportion of CR's suggests that this program may prove to be an organ-sparing and curative approach for a significant number of patients, but more experience and follow-up are required.

Adult↗
PubMed1983

Ultrasonic and jet aerosolization of phospholipids and the effects on surface activity.

Surface active aerosols were produced from aqueous dispersions of mixed lipids (CLL), extracted from bovine lung lavage. Particle size distributions were measured as a function of humidity for two types of aerosol generators: ultrasonic and jet. Lipid dispersions before aerosolization were prepared by sonication in an ice bath and by mechanical vortexing. Over a range of high humidity greater than 60-70%, ultrasonic nebulization gave CLL aerosols with mass median aerodynamic diameters (MMAD) of 1.4 +/- 0.1 micron, compatible with predicted alveolar deposition fractions of 0.2-0.3 according to current deposition models. For humidities of 30-95%, jet nebulization gave MMAD values of 0.4-0.5 micron, which have lower predicted alveolar deposition. The surface pressure-time (pi - t) adsorption characteristics at 35 +/- 2 degrees C of CLL dispersions prepared initially by vortexing or sonication were not significantly affected by ultrasonic nebulization over a 1-2 h time period. In addition, the dynamic surface tension lowering of both kinds of CLL dispersion was not affected by ultrasonic nebulization (minimum surface tension less than 1 dyne/cm at 37 degrees C and 100% humidity). Current interest in the treatment of the respiratory distress syndrome (RDS) with exogenous surfactant replacement has focused largely on the delivery of surfactant replacement has focused largely on h delivery of surfactants to infants by tracheal instillation at birth. However, the ability to form multi-component surfactant aerosols with appreciable alveolar deposition fractions and high surface activity may help to expand the utility of replacement therapy to patients with aerated lungs.

Adsorption↗
PubMedDate not supplied

Assessing the impact of elective regional radiotherapy on survival.

PURPOSE: Elective regional irradiation (ERI) of sites of likely tumor spread has been common radiation oncology practice for decades. It is based, in part, on the assumption that cancer often spreads in an orderly fashion and that an improvement in regional control will increase survival. METHOD: The clinical data regarding the impact of ERI on local-regional control vs survival are reviewed for a variety of tumor sites. RESULTS: Improvements in survival with ERI have been reported in some clinical situations. For most, however, survival improvements have been difficult to realize. In most clinical situations, the realistic improvement in survival that is achievable with ERI is small and would be difficult to document in reasonably sized clinical trials. DISCUSSION: The dose-response relationship for the impact of ERI on survival is discussed. A hypothesis suggesting that a reduction in the dose of ERI may improve the therapeutic ratio of ERI (with respect to its impact on survival) is presented.

Dose-Response Relationship, Radiation↗