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H Suit

Publications and source records attributed to H Suit.

At least 19 recordsLinked to original sources
PubMed1999

Radiation treatment of benign mesenchymal disease.

The benign mesenchymal diseases, for which radiation is often quite effective in halting progression or achieving complete and permanent resolution, include neoplastic and nonneoplastic processes (eg, giant cell tumor of bone to keloid). Radiation oncologists have been reluctant to employ radiation in the management of patients with benign disease for several reasons: (1) the small but nonzero risk of late appearance of radiation-induced malignant tumors; (2) were radiation subsequently required to be employed in the same region of the body for treatment of a separate and independent neoplasm, the radiation dose might have to be reduced to an ineffective level; and (3) nonmalignant tissue changes that might appear at quite remote times and complicate healing of surgical wounds. Currently a liberalization of the use of radiation is in progress because of the clinical seriousness of many benign processes for which radiation yields a major therapeutic benefit. This reassessment of radiation oncology in the United States has been stimulated by the much wider application of radiation for patients with a wide spectrum of benign diseases in several European countries. This article considers the major indications and the expected outcomes from radiation treatment of benign mesenchymal diseases. For benign neoplasms that are locally progressive, the radiation dose is usually in the range 50 to 60 Gy administered at 1.8 to 2.0 Gy/fraction, five fractions per week. The response is characteristically quite slow, and the long-term local control probability is high (80%). Further, the response probability is not sensitive to lesion size, in contrast to malignant tumors of the mesenchymal tissues. For the nonneoplastic processes managed in some instances by radiation, the doses recommended are usually in the range of 6 to 12 Gy as single-dose or 20 to 25 Gy as fractionated dose irradiation. The efficacy of such treatment tends to be equal to or less than that noted for the benign neoplastic diseases.

Adult↗
PubMed1996

Radiation in management of patients with dermatofibrosarcoma protuberans.

PURPOSE: The preferred treatment of dermatofibrosarcoma protuberans (DFSP) is wide resection, namely, margins > or = 3 cm beyond the evident disease and histologically negative margins. We assess the success achieved by radiation combined with surgery for positive/close margins or by radiation alone for those tumors that are not resectable for technical/medical reasons. The literature on this point is virtually nonexistent. MATERIALS AND METHODS: The outcome of treatment of 18 patients with DFSP by radiation alone (n = 3) and radiation and surgery (n = 15) at the Massachusetts General Hospital was assessed. All of the lesions at the time of the treatment by radiation alone or combined with surgery were less than 10 cm. This was the maximum dimension. The actual tumor volume was much less than indicated by this maximum dimension, as the tumors were usually relatively flat. RESULTS: The 10-year actuarial local control rate was determined to be 88%. Local control was realized in the three patients treated by radiation alone, with follow-up periods of > or = 9 years. Among 15 patients treated by radiation and surgery, there have been three local failures; the 10-year actuarial local control rate was 84%. The three local failures occurred in 12 patients whose surgical margins were positive. One of these three local failures developed in the group of two patients whose lesions were scored as grade II. CONCLUSION: Radiation in well-tolerated dose schedules is an effective option in the management of patients with DFSP. This appears to be true for radiation alone or postoperatively for margin-positive disease (primary or recurrent).

Adult↗
PubMed1996

The effect of whole-body irradiation of nude mice on the tumor transplantability and control probability of a human soft tissue sarcoma xenograft.

This study has evaluated the impact of the suppression and recovery of the residual immunity in NCr/Sed nude (nu/nu) mice after whole-body irradiation using xenotransplantability and tumor control probability as the end points. For this investigation the xenograft was a human soft tissue sarcoma (HSTS26T). Two assays, the TD50 (the number of tumor cells required to induce a tumor in 50% of the recipients) and the TCD50 (the radiation dose required to control 50% of tumors) were used. For TD50 assays, tumor cells were injected subcutaneously (sc) into the legs of control and whole-body- irradiated nude mice at 1 day or 4, 8 or 12 weeks after irradiation. For TCD50 assays, tumors were transplanted sc into the legs of nude mice which had not been irradiated or which had been given whole-body irradiation at 1 day or 12 weeks prior to transplantation. The tumors were given single-dose irradiation when they reached 6 mm mean diameter under clamp-hypoxic conditions. The results show that the TD50's of mice receiving the injection 1 day and 4 and 8 weeks after whole-body irradiation were 3.6 to >100 times lower than that of unirradiated mice. Two groups which showed a statistically significant difference in TD50 's were those which received the injection 1 day and 8 weeks after whole-body irradiation (P < 0.01 and P < 0.05, respectively). No difference was found in TD50 values between mice that received injection 12 weeks after whole-body irradiation and those which were not irradiated. The TCD50 values of tumors in nonirradiated mice and in mice which had received whole-body irradiation 1 day and 12 weeks prior to to transplantation were 26.8, 44.1 and 33.9 Gy, respectively. Significantly lower TCD50 values were found in groups of nonirradiated mice or mice which received whole-body irradiation 12 weeks prior to transplantation in comparison with the group of mice that received whole-body irradiation on day 1 (both P < 0.05). No significant difference was found between the TCD50 values of the group of mice that received whole-body irradiation 12 weeks prior to transplantation and those for nonirradiated controls. Our conclusion is that the whole-body irradiation can enhance the transplantability of the HSTS26T tumor in nude mice significantly; this enhancing effect will decrease to the pre-irradiation level by 12 weeks after whole-body irradiation. Also, the suppression and recovery of residual immunity after whole-body irradiation can influence the TCD50 values of the same tumor xenografts in nude mice significantly. The changes in TD50 and TCD50 values correlate with the depletion and recovery of the total splenic lymphoid cell number, and especially in natural killer cell activity. We recommend that further immunosuppression in nude mice is necessary when using this model system for studies of human tumors.

Animals↗
PubMed1996

Soft tissue sarcomas: radiation as a therapeutic option.

There is continuing assessment to find the most effective management strategy for primary soft tissue sarcomas. The goal of treatment for any patient with malignant neoplasm is to provide a tumour-free survival without clinically appreciable treatment-related morbidity. For most adult patients, this currently is attempted by a combination of relatively conservative surgery and moderate dose of radiation. The concept being that radiation at dose levels of 50 to 60 Gy is adequate to inactivate the tumour cells which lie beyond the margins of a conservative resection, i.e., it replaces the resection of large volumes of normal tissue. Laboratory measurements of radiation sensitivity of cell lines derived from sarcomas of soft tissue tumours have shown that they are not radiation-resistant relative to the cell lines derived form epithelial tumours. Hence, there is no surprise the this combined modality approach has been demonstrated to be effective. The frequency of local control (85% to 90%) is at least as high as that combined by ablative surgery, but with much lesser decrement in functional and cosmetic status. Additionally, radiation at dose levels of about 75 Gy is effective in achieving worthwhile local control rates when administered against small sarcomas of the soft tissues, e.g. volumes of < or = 60 ml. Thus, for selected tumours, radiation alone does offer a reasonable option when surgery is not feasible for technical reasons or the patient is not operable for medical reasons. Available data do not indicate a clear advantage for adjuvant chemotherapy for this group of tumours. Trials are in progress to assess the efficacy of neo-adjuvant chemotherapy. We are conducting a phase II trial of MAID chemotherapy and radiation preoperatively; the results to date are superior to matched concurrently treated patients. For local therapy, high and approximately comparable local control rates are being reported for several approaches: radical compartmental resection for selected patients, surgery and postoperative radiation therapy, surgery and preoperative radiation treatment, resection and intraoperative placement of catheters for brachytherapy and intra-arterial adriamycin, radiation and resection. Our preferred approach for T 2, grades II-III sarcomas of the soft tissues is radiation prior to surgery. There are, however, no data on the functional and cosmetic status after treatment of patients whose sarcomas are of a specified site and volume for treatment by these diverse methods. This is a critically important question in the assessment of proper clinical role of each of these approaches.

Adult↗
PubMed1995

In vivo radiation sensitivity of glioblastoma multiforme.

PURPOSE: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. METHODS AND MATERIALS: The TCD50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. RESULTS: The TCD50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 +/- 13.1 Gy. The TCD50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 +/- 6.4. The difference between the average TCD50 of GBM and SCC was not significant. The STS and CC xenografts had TCD50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD50 in vivo and the SF2 or D0 in vitro. CONCLUSIONS: Our data on GBM xenografts showed a wide range of sensitivities to single dose irradiation in vivo, which does not correlate with the almost invariably fatal clinical outcome of these patients. No correlation was observed between the TCD50 in vivo and the in vitro SF2/D0 of the corresponding cell lines. Our in vivo and in vitro data on GBM suggest that radiation sensitivity alone does not explain the cause of the poor clinical response of GBM to radiation, and other factors could contribute to this response.

Animals↗
PubMed1995

Base of skull and cervical spine chordomas in children treated by high-dose irradiation.

PURPOSE: To evaluate the outcome of children with base of skull or cervical spine chordomas treated by high dose irradiation. METHODS AND MATERIALS: Eighteen children, 4 to 18 years of age, with base of skull or cervical spine chordomas, received fractionated high-dose postoperative radiation using mixed photon and 160 MeV proton beams. The median tumor dose was 69 Cobalt Gray-equivalent (CGE) with a 1.8 CGE daily fraction. RESULTS: The median follow-up was 72 months. The 5-year actuarial survival was 68% and the 5-year disease-free survival (DFS) was 63%. The only significant prognostic factor was the location: patients with cervical spine chordomas had a worse survival than those with base of skull lesions (p = 0.008). The incidence of treatment-related morbidity was acceptable: two patients developed a growth hormone deficit corrected by hormone replacement, one temporal lobe necrosis, and one fibrosis of the temporalis muscle, improved by surgery. CONCLUSION: Chordomas in children behave similarly to those in adults: children can receive the same high-dose irradiation as adults with acceptable morbidity.

Adolescent↗
PubMed1995

Regaud Lecture, Granada 1994. Tumors of the connective and supporting tissues.

There has been a continuous acceleration of medical/scientific inquiry and of actual improvements in management of patients with neoplasms of the mesenchymal tissues over the last four decades. The number of publications in this field has increased from 1140 in 1970 and then to 1700 in 1990. Important advances discussed over this period include: establishment of sarcoma teams in major oncology centers; staging systems for both soft tissue and osseous sarcomas; demonstration of genetic determinants in the development of, at least, some of the sarcomas; the revolutionary change in quality of diagnostic imaging by the introduction of CT and MRI; use of immunohistochemistry in diagnostic pathology; the drastic gains in survival of patients with osteogenic sarcoma, Ewing's sarcoma and rhabdomyosarcoma due to the efficacy of multi-drug and multi-cycle chemotherapy protocols; major advances in surgical techniques which have made limb salvage practical; cell lines derived from human sarcomas have been shown to have in vitro radiation sensitivity comparable to that of cell lines from epithelial tumors; the combination of conservative surgery and moderate doses of radiation yields local control and survival results equivalent to that of radical surgery with a much improved functional and cosmetic outcome; intra-operative electron beam radiation therapy improves the outcome of patients with retroperitoneal sarcomas when given after grossly complete resection combined with external beam radiation therapy (pre- or postoperatively); radiation is a highly effective alternative to extensive surgery for desmoid tumors; local control of giant cell tumors by modern radiation techniques is approximately 80% and the incidence of radiation induced tumors at 10 years is approximately 3%; to decrease the incidence of radiation induced sarcoma, resection has replaced radiation in the management of selected patients with primary Ewing's sarcoma when the response to chemotherapy has been excellent and the morbidity/functional decrement consequent upon the surgery judged reasonable; proton beam radiation therapy has been accepted as being superior to conventional external beam radiation therapy for chondrosarcoma and chordoma of the skull base; and attempts to utilize brachytherapy for sarcomas of the spine/sacrum appear to offer promise. Projected advances in the coming two decades includes:Designation of sarcoma type on genetic characterization; molecular genetics will provide prognostic information as to probability of distant metastasis, response to chemotherapeutic agents and radiation; important further reductions in the radiation treatment volume due to the many technical developments entering, or soon to enter the clinic; non-invasive assessment of the response to chemotherapy; much increased appreciation of the late sequella of treatment, both radiation and chemotherapy.

Humans↗
PubMed1995

Combined surgery and radiation therapy for limb preservation in soft tissue sarcoma of the extremity: the Massachusetts General Hospital experience.

The results presented here indicate that excellent local control rates can be achieved using radiation in combination with limb-sparing surgery. At least three challenges remain and need to be addressed in future prospective trials. One is the need to reduce wound complications. In this regard, the influence of chemotherapy on the healing of the irradiated wound needs to be better defined as well as the role of recombinant growth factors and cytokines in tissue repair. Second is the need to better assess functional and psychological outcome in patients who are long-term survivors as well as in patients who succumb to distant disease. Despite the limited information on this end-point, it appears that strategies that reduce wound morbidity ultimately have a beneficial outcome with regard to functional and psychological status. Third, our greatest challenge is to improve the rates of distant disease control. Despite excellent local control rates following limb-sparing procedures, greater than 50% of patients will ultimately die of their disease. New systemic therapies must be developed to control systemic dissemination. The ultimate goal of combined surgery, radiation, and chemotherapy will be to preserve limb function in patients who are cured of their disease.

Brachytherapy↗
PubMed1995

Radiation as a therapeutic modality in sarcomas of the soft tissue.

Management of the primary lesion in patients with soft tissue sarcomas is combined modality in the majority of instances. The modalities are surgery and irradiation. Radical surgery as currently practiced in major oncology centers does not achieve local control in an important proportion of patients.

Actuarial Analysis↗
PubMed1994

Is tumor cell radiation resistance correlated with metastatic ability?

Patients who experience local failure following radiation treatment of epithelial malignancies exhibit a substantially higher rate of distant metastasis than those patients who achieve permanent local control. This fact has raised concern that the local failure to control the primary/regional tumor may serve as a marker of a particularly malignant neoplasm, i.e., high metastatic activity and radiation resistance. If this were true, there would be no gains in survival by increasing the efficacy of treating the primary/regional disease because the new local controls would develop distant metastasis. To investigate this concept, the relationship between distant metastasis probability and tumor cell radiation resistance has been studied by examining laboratory and clinical data (in vitro and in vivo assays) from six collaborating centers. TCD50s (radiation dose which inactivates half of the irradiated tumors) and incidence of distant metastasis in mice with local control have been evaluated for 24 murine tumor systems. SF2s (surviving fraction after 2 Gy) were determined in vitro for cell lines from 8 human, 13 mouse, and 15 rat tumors/tumor sublines and the metastatic activity assessed after injection of the cells into syngeneic murine hosts and xenogenic hosts for the human tumors. SF2s of cells from carcinomas of the head/neck, cervix, and endometrium which were controlled locally by radiation +/- surgery from four centers were compared for those which did and those which did not metastasize. The total number of patients studied was 222. The cumulative distributions of SF2s of locally controlled tumors which did and did not metastasize were not different in each of the data sets. Similarly, there was no demonstrable relationship between TCD50s and metastatic frequency in local control mice. Furthermore, the SF2s of murine and human tumor cell lines did not track with metastatic activity. Radiation sensitivity of clinical and laboratory tumors did not correlate with metastatic activity in studies of data from six centers.

Animals↗
PubMed1993

Intrinsic radiation sensitivity may not be the major determinant of the poor clinical outcome of glioblastoma multiforme.

PURPOSE: Many radiobiologic mechanisms may contribute to the clinical radiation resistance of Glioblastoma Multiforme. One of them is considered to be an unusually low intrinsic radiation sensitivity. This is a collaborative study between three laboratories to evaluate the intrinsic radiation sensitivity of 85 cell lines derived from human malignant gliomas as the major cause of the poor clinical results of radiation treatment to these tumors. METHODS AND MATERIALS: Fifty-one cell lines were early passage. The distribution by histologic type was: 58 glioblastoma, 17 anaplastic astrocytoma, six oligodendroglioma and four astrocytoma grade 2. The intrinsic radiation sensitivity will be expressed by the surviving fraction at 2 Gy (SF2). The SF2 has been determined for single dose irradiation for cell lines on exponential phase, under aerobic conditions, growing on plastic. The patient age, Karnofski Status, histological grade, survival, dose of irradiation for 50 patients are investigated for correlation with SF2 of the corresponding newly established cell lines. RESULTS: The mean SF2 of the 85 cell lines was 0.46 (0.12-0.87). The mean SF2 by histologic type was 0.50, 0.34, 0.54 and 0.38 for glioblastoma, anaplastic astrocytoma, oligodendroglioma and astrocytoma grade 2 cell lines, respectively. No correlation was found between SF2 and the patient age or Karnofski status. The difference in SF2 between the 58 glioblastoma and 17 anaplastic astrocytoma cell lines was significant p = 0.002. The difference in actuarial survival between glioblastoma and anaplastic astrocytoma patients was borderline of significance (p = 0.08). The difference in SF2 of cell lines derived from these two groups of patients was of borderline significance (p = 0.08). The difference in radiation sensitivity for anaplastic astrocytoma and glioblastoma cell lines was clearly reflected in the difference in survival for the two groups of patients from where the cell lines were derived. However, no correlation was found between SF2 and survival within each grade. In a multivariate analysis the age, grade and Karnofski status were found to be significant prognostic values for survival with a p values of 0.032, 0.03 and 0.038, respectively, however, the ln SF2 was not significant (p = 0.40). The mean SF2 of the 6 oligodendroglioma cell lines (0.54) was comparable to that of glioblastoma multiforme (0.50). The high SF2 for oligodendroglioma does not accord with the much better clinical outcome of these tumors. CONCLUSIONS: These data on 85 malignant glioma cell lines show a very broad distribution of SF2 values for irradiation in vitro. SF2 reflected the difference in sensitivity between AA (Grade 3) and GBM (Grade 4). This may suggest that the parameter SF2 is useful to discriminate between the sensitivity of different grades or types of histology in vitro. However, SF2 was not a predictor of the clinical outcome on individual basis for malignant gliomas. The in vitro studies will need to be supplemented by physiologic characterization of the tumors in vivo. Such conclusions would limit the predictive value of current radiation sensitivity assays based on in vitro dose-survival measurement for at least high grade malignant gliomas.

Astrocytoma↗
PubMed1993

In vitro split-dose recovery of glioblastoma multiforme.

Glioblastoma multiforme is among the most clinically resistant tumors to radiation. This resistance may be due to several different factors, such as a low intrinsic radiation sensitivity, a high recovery capacity, an increased number of clonogens, and a high hypoxic fraction. Previously, we have demonstrated a very wide range of intrinsic radiation sensitivities of cells of glioblastoma multiforme cell lines in vitro after single-dose irradiation. That is, the cells of some glioblastoma multiforme cell lines were quite sensitive, while for others the sensitivity of glioblastoma multiforme was among the lower range of sensitivities reported in the literature. This finding indicates that inherent cellular radiation sensitivity is not the sole determinant of the in vivo response of glioblastoma multiforme tumors. In this report, we evaluate the role of split-dose recovery determined in vitro in relation to the poor clinical outcome of glioblastoma multiforme. Cells of seven early-passage glioblastoma multiforme cell lines and six cell lines derived from tumors of a type frequently treated successfully (two squamous cell carcinomas of head and neck, three breast cancers, and one low-grade astrocytoma cell line) were studied. The in vitro split-dose recovery has been measured using colony formation as an end point. The cells were maintained at 37 degrees C for a period of 6 h between the doses of radiation. Results are presented in terms of a recovery ratio: the ratio of the mean inactivation dose of split-dose radiation to that of single-dose radiation. The data show significantly higher recovery ratios for glioblastoma multiforme than for the other types of histology; however, glioblastoma multiforme showed a wide range of recovery ratios, varying from 1.12 to 2.02. This indicates that cells of some glioblastoma multiforme cell lines exhibit minimal split-dose recovery. No correlation was found between the recovery ratio and the intrinsic radiation sensitivity of the cell lines studied. From these data, we conclude that the recovery capacity may not be the major determinant of the clinical radiation resistance of some glioblastoma multiforme.

Cell Survival↗