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Biomedical subjects

S Hellman

Publications and source records attributed to S Hellman.

At least 91 records · Page 5Linked to original sources
PubMed1987

Fractionation and dose rate effects in mice: a model for bone marrow transplantation in man.

This study was designed to compare several fractionation and dose rate schedules to optimize the therapeutic ratio for total body irradiation (TBI). C3H/HeJ mice were given TBI and the bone marrow survival fraction was calculated using the CFUS assay. Irradiation was given at two dose rates: low dose rate (LDR) at 5 cGy/min or high dose rate (HDR) at 80 cGy/min in single fraction and fractionated regimens. The fractionated regimens were given as either 120 cGy three times daily, 200 cGy twice daily, or 200 cGy daily. The Do was 80 cGy for the single fraction, HDR group and 85 for the LDR group. For the fractionated regimens, the apparent Do's ranged from 55-65 indicating no sparing effect of fractionation for the normal bone marrow stem cells. Indeed, the Do's were smaller suggesting an increased sensitivity to irradiation with fractionation. Low dose rate (LDR) and fractionation were also studied for their influence on normal tissue toxicity following upper half body irradiation (UHBI). All the fractionated regimens had higher LD50/30 and LD50/30-180 values than those achieved by single fraction LDR alone. There was no significant dose rate effect for LD50/30 when 120 or 200 cGy fractions were used. However, dose rate was important for LD50/30-180 with 200 cGy but not with 120 cGy fractions. These results demonstrate protection of non-hematopoietic tissues with fractionation and low dose rate without protecting hematopoietic stem cells and may have implications for human bone marrow transplantation.

Animals↗
PubMed1987

Limited resection for breast cancer: a study of inked specimen margins before radiotherapy.

This is an analysis of tumor margins of 108 patients who underwent a limited resection for infiltrating breast cancer, prior to starting radiation therapy. This represented the initial resection (IR) in 75 patients, and a re-excision (RE) after biopsy elsewhere in 33 patients. All specimens were processed by the India ink method prior to frozen and paraffin section analysis. Overall, the incidence of involved margins was 28% for the IR group, and 15% for the RE group. No correlation was found with the axillary node status, or with the type of prior surgery in the RE group. The data suggest a correlation between increasing tumor size and margin involvement. Further surgery in the IR group with involved margins yielded negative margins in all cases; the finding of residual carcinoma was correlated with the type of secondary surgery, that is, further re-excision or mastectomy.

Biopsy↗
PubMed1987

Engraftment following T-cell-depleted marrow transplantation. I. The role of major and minor histocompatibility barriers.

These experiments describe a murine model for survival and engraftment of bone marrow transplantation across differing histocompatibility barriers. Anti-Thy-1.2 antibody and complement-treated C57BL/6 (B6) marrow was transplanted at varying cell dose levels into syngeneic (B6), major histocompatibility complex congenic (A.BY), semiallogeneic (B6AF1), and fully allogeneic (A/J) recipients. Survival was monitored and engraftment determined by hemoglobin and lymphocyte phenotype. Survival was cell-dose dependent and was equivalent in B6, A.BY, and B6AF1 recipients. Survival was poor in allogeneic A/J recipients due to bone marrow failure even at high marrow dose levels. Survival posttransplant did not always correlate with stable donor engraftment, and competitive host marrow repopulation was frequently seen in B6AF1 recipients but rarely in A.BY recipients. This repopulation could be prevented by transplanting a larger marrow dose.

Animals↗
PubMed1987

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy.

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Are prognostic factors for local control of breast cancer treated by primary radiotherapy significant for patients treated by mastectomy?

Recent follow-up studies of patients with mammary carcinoma treated with breast-conserving primary radiotherapy identified a triad of pathologic features significantly associated with local treatment failure. These unfavorable characteristics of the primary tumor were: poor or undifferentiated nuclear grade; intraductal carcinoma within the tumor mass; and intraductal carcinoma in breast tissue outside the perimeter of the primary lesion. The current study was undertaken to assess the impact of these same factors on the prognosis of 573 consecutively treated women, with invasive duct carcinomas 5 cm or less in diameter, and who underwent mastectomy. Histologic sections of all primary tumors were reviewed, and the lesions were classified according to the distribution of intraductal carcinoma present: only within the tumor (IN, 247 cases, 43%), only outside the tumor (OUT, 25 cases, 4%), within the outside (IN-OUT, 158 cases, 28%), or not seen (IFDC, 143 cases, 25%). The median follow-up period for the entire series was 56 months. Ninety-five (17%) patients were dead of disease (median time to death, 36 months). Variables that proved to be statistically significant for overall survival were nodal status (P less than 0.001), nuclear grade (P less than 0.03), and histologic grade (P less than 0.007). Nodal status (P less than 0.001), histologic grade (P less than 0.001), and tumor size (P = 0.01) were significant predictors of disease-free survival. The pattern of intraductal carcinoma, when present, was not predictive of the risk for recurrence or survival in women treated by mastectomy. These findings provide a rationale for additional surgical treatment for women whose tumors have features more likely to be associated with local failure following primary radiotherapy. To permit more detailed pathologic examination of the primary lesion, the initial excision should be carried out separately from the treatment when limited resection and radiation are to be considered as a treatment option.

Breast Neoplasms↗
PubMed1986

Observations on survival curve analysis with particular reference to breast cancer treatment.

The proper analysis of survival curves of patients treated for cancer is critical to advances in clinical investigation. In this article, the presentation of such survival curves is reviewed and the various possible effects of treatment on these curves are discussed. The results of breast cancer treatment are used as examples. It is argued that the use of a semilogarithmic presentation is preferred in displaying the long-term force of mortality of the disease. In many human cancers, such as carcinoma of the breast, the demonstration of a "cured" subgroup requires follow-up of greater than 10 years and cannot be inferred from data evaluated earlier. Beneficial effects noted on the initial portion of the survival curve are not necessarily associated with an improvement in the likelihood of long-term survival, but are rather a reflection of delay or reduction on the initial force of mortality. Since both hosts and tumors are heterogeneous, it is also possible that there are different effects on various subgroups, making curve interpretation complex. In some cases, an early detrimental effect may obscure a benefit in the long-term outcome. These considerations emphasize that effects seen on the early portion of survival curves may not only be premature, but may also be misleading.

Actuarial Analysis↗
PubMed1985

Stage IA to IIB supradiaphragmatic Hodgkin's disease. Long-term survival and relapse frequency.

Long-term survival and prognostic factors were analyzed in 307 patients with pathologically staged IA to IIB supradiaphragmatic Hodgkin's disease (HD). Treatment with radiation therapy (RT) alone resulted in a 10-year actuarial freedom from first relapse (FFR) of 88% and 10-year survival of 95% for Stage IA patients and a FFR and survival of 76% and 93%, respectively, for Stage IIA patients. Stage IB to IIB patients had similar survivals when treated with combined-modality therapy (CMT) (85%) or RT alone (77%). Stage IA to IIB patients with large mediastinal adenopathy (LMA) treated with RT alone had a significantly worse survival as compared with patients with lesser or no mediastinal adenopathy, 83% versus 94%, respectively, P = 0.006. Initial CMT for patients with LMA resulted in an improved FFR as compared with patients treated with RT alone, 83% versus 49%, respectively (P = 0.05); however, no differences in survival were seen. Other prognostic factors are analyzed. These data support the initial use of Rt alone in early-stage Hodgkin's disease patients. CMT should only be used for selective patients, such as those with LMA in which the volume to be irradiated is large. In these patients, initial chemotherapy followed by irradiation may allow treatment of small volumes of heart and lung.

Adolescent↗
PubMed1985

Breast relapse following primary radiation therapy for early breast cancer. I. Classification, frequency and salvage.

Primary radiation therapy has become an accepted alternative to mastectomy for patients with early breast cancer. In order to improve the results of this treatment, we performed an analysis of failure on 366 clinical Stage I or II invasive breast carcinomas treated with primary radiation therapy. With a median follow-up of 52 months, there have been 30 recurrences in the treated breast, for a 5 year actuarial local recurrence rate of 9%. The recurrence rate was much higher for patients having less-than-excisional biopsy than for those undergoing excisional biopsy (35% vs. 7%, p less than 0.0001). Failures in the treated breast have been categorized as: true recurrence (TR), directly at the site of the primary; marginal miss (MM), at the edge of the boosted volume; and elsewhere in the breast (E). For patients having excisional biopsy, the actuarial probability of a true recurrence at 5 years was 4%. The risk of a true recurrence was related to the dose given to the primary site with rare true recurrences seen with doses greater than 6000 rad. The probability of a marginal miss at 5 years was 4%, and was not related to the dose or volume of the boost used. The probability of a recurrence elsewhere in the breast at 5 years was 1%. In patients treated with excisional biopsy and a total primary dose over 6000 rad, the probability of a local recurrence at 5 years was 4 and 10% for clinical Stage I and II patients respectively. These results indicate that primary radiation therapy provides a high likelihood of local tumor control and our analysis of failure suggests methods for decreasing each type of local recurrence.

Adult↗
PubMed1985

The use of pathologic features in selecting the extent of surgical resection necessary for breast cancer patients treated by primary radiation therapy.

The extent of the surgical resection necessary for breast cancer patients treated by primary radiation therapy is unknown. A simple gross excision of the tumor provides the best cosmetic result, but a wide local resection may be important to prevent local recurrence in some patients. In order to identify patients who are not adequately treated by gross excision of the tumor and radiation therapy, we performed a retrospective clinical-pathologic review of 221 treated women with infiltrating duct carcinoma. There were 53 cases in which the excision specimen showed a constellation of three pathologic features: prominent intraductal carcinoma in the tumor, intraductal carcinoma in the grossly-normal adjacent tissue, and poorly-differentiated nuclei. These cases had a 37% risk of a local recurrence at 6 years compared to eight per cent for all other cases (p less than 0.0001). In cases with all three features, the use of a supplemental dose of radiation to the primary site did not significantly reduce the risk of a local recurrence. Local recurrence at 6 years was 34% in cases with all three features, who received supplemental local radiation, compared to 49% in cases not receiving a supplemental dose (p = 0.28). Survival was also worse for patients with all three features compared to other cases (69% vs. 90% at 6 years, p = 0.002). These results indicate that patients with all three pathologic features have a high risk of local recurrence following gross excision of the tumor and radiation therapy. If primary radiation therapy is selected for these patients, they should first undergo a re-excision of the tumor site in order to be certain that areas of extensive intraductal carcinoma have been adequately resected. Patients whose tumors do not show all three features are adequately treated by gross excision of the tumor prior to radiation therapy.

Breast↗
PubMed1985

Improved survival following combined radiation therapy and chemotherapy for unfavorable prognosis stage I-II non-Hodgkin's lymphomas.

A retrospective analysis of 144 patients with stage I-II non-Hodgkin's lymphoma (NHL) treated between June 1968 and December 1980 was performed. Patients were staged by bone marrow biopsy, chest radiography, blood chemistries, and either bipedal lymphangiography, computerized axial tomography, or surgical exploration of the abdomen. Patients were subclassified by extent of disease; minimal disease was defined as less than 10 cm and involved one or two contiguous sites, while patients with disease exceeding these limitations were considered to have extended stage I-II disease. Treatment consisted of radiation therapy (RT) alone in 74 patients and 70 patients were treated with chemotherapy with or without RT. Combination chemotherapy in patients with diffuse undifferentiated (DU) or diffuse histiocytic (DH) lymphoma resulted in a significantly higher 6-year survival as compared to patients treated with RT alone. For minimal disease DU/DH patients, the 6-year survival with chemotherapy +/- RT was 96% as compared to 61% with RT alone (P = .03). For extended disease DU/DH patients the 6-year survival with chemotherapy +/- RT was 56% as compared with 18% with RT alone (P = .003). This survival advantage from the initial use of chemotherapy was not seen in any of the other histologic subgroups.

Adolescent↗
PubMed1985

Reduction of fatal complications from combined modality therapy in Hodgkin's disease.

A total of 464 pathologically staged IA through IIIB Hodgkin's disease patients were evaluated for the risk of developing acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, or a fatal infection after treatment with radiation therapy (RT) alone, initial combined radiation therapy and chemotherapy (CMT), or RT with MOPP administered at relapse. Patients received a standard six cycles of MOPP, and additional maintenance chemotherapy was not administered. Patients receiving total nodal irradiation (TNI) and MOPP chemotherapy have an 11.9% actuarial risk of developing a fatal complication at ten years, as compared to a 0.8% risk for lesser field irradiation and MOPP (P = .005). The risk with RT alone is 0.6%. Patients 40 years of age or older have a greater risk for complications. These data report a low risk for fatal complication with CMT when less than TNI is administered and when maintenance chemotherapy is not used.

Actuarial Analysis↗