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H Suit

Publications and source records attributed to H Suit.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1992

Proton beams in radiation therapy.

The rationale for study of proton radiation therapy is that, for some anatomic sites and tumors, the treatment volume is smaller; i.e., there is less irradiation of nontarget tissue while the target is included in three dimensions at each treatment session. As a result, the dose to the target can be raised. The consequence is that the tumor control probability improves and the frequency and severity of treatment-related morbidity decrease. These results come about from the physical fact that the proton range in tissue is finite; in comparison, absorption of photons is an exponential function and, hence, some dose is received for the full-beam path through the body. Accordingly, the dose deep to the target for proton treatments can be zero for each beam path. This situation provides a virtually certain means of improving the treatment outcome for selected categories of patients. Experience to date with proton radiation therapy has been quite limited. As of June 1991, the total number of proton radiation-treated patients was 11,763 from the various centers. Of that number, approximately 46% and 32% have been treated for small benign intracranial lesions (principally pituitary adenomas and arteriovenous malformations) and for tumors of the eye, respectively. Thus, only some 2500 patients have been treated for all other tumor types. The results from three centers and approximately 2800 patients with uveal melanoma are that the local control rate was 96% (for failures in-field, marginal, and in other parts of the eye). The local control results for chondrosarcomas and chordomas of the skull base are 91% and 65%, respectively. These percentages compare with some 35% achieved with conventional treatment. Experience with arteriovenous malformations indicates that control of bleeding and disappearance of the lesion are comparable to those achieved by other procedures. The developments from the proton therapy programs have contributed greatly to radiation treatment planning, e.g., the first three-dimensional treatment planning system put into regular clinical use (uveal melanoma), beam's eye view, digital-reconstructed radiograph, dose-volume histograms, and definitions of the uncertainty in dose around any defined point. The potential for clinical gains is high. In May 1991, the Proton Radiation Oncology Group was formed to design, supervise, and coordinate clinical trials and to assist in data analysis. The efficacy of proton radiation therapy will be compared with that of photon therapy of the very highest technology.

Arteriovenous Malformations↗
PubMed1992

Clinical implications of heterogeneity of tumor response to radiation therapy.

Heterogeneity of response of tumor tissue to radiation clearly exists. Major parameters include histopathologic type, size (number of tumor rescue units (TRUs)), hemoglobin concentration, cell proliferation kinetics and immune rejection reaction by host. Further, normal and presumably tumor tissue response is altered in certain genetic diseases, e.g. ataxia telangiectasia. Any assessment of response of tumor tissue to a new treatment method or the testing of a new clinical response predictor is optimally based upon a narrow strata, viz., uniform with respect to known parameters of response, e.g. size, histological type. Even among tumors of such a clinically defined narrow strata, there will be residual heterogeneity with respect to inherent cellular radiation sensitivity, distributions of pO2, (SH), cell proliferation etc. The value of a response predictor of an individual tumor will be determined by the heterogeneity of values for these and or other characteristics and by the coefficient of variation (CV) of the measured values of the individual parameters. Heterogeneity of one or more parameters of response is reflected in the slope of the dose response curve for local control, viz. the greater the heterogeneity the less steep the slope. To examine for this effect, the slope of dose response curves for control of model tumors of 10(8) tumor rescue units (TRU) and the SF2 = 0.5 (survival fraction after a single dose of 2 Gy) has been used to assess the impact of inter- and intra-tumoral variation of SF2 on slope, defined as gamma 50 values. The gamma 50 is the increase in local control expressed in percent points for a one percentage increment in dose, at the mid-point on the dose-response curve. The gamma 50 was 6.5 for CV = 0.0. For inter-tumoral CVs of 10%, 20% and 40%, the gamma 50 rapidly decreased to 2.4, 1.3 and 0.7. Intra-tumoral variation was less important, viz., for CVs of 10%, 20%, and 40% the gamma 50 values were reduced to 5.3, 3.8 and 2.2. Combining inter- and intra-tumoral variation reduced the gamma 50 only slightly below that for inter-tumoral variation alone. For example, were the CV 10% for inter- and intra-tumoral variation, the gamma 50 would be 2.1 as compared to 2.4 for inter-tumoral variation alone. The number of TRUs also affects slope, viz. gamma 50 increased from 1 to 9.7 as the TRU number increased from 10(1) to 10(12).(ABSTRACT TRUNCATED AT 400 WORDS)

Dose-Response Relationship, Radiation↗
PubMed1992

In vitro intrinsic radiation sensitivity of glioblastoma multiforme.

Glioblastoma multiforme is one of the most resistant of human tumors to radiation whether used alone or in combination with surgery and/or chemotherapy. This resistance may be caused by one or more of several different factors. These include inherent cellular radiation sensitivity, an efficient repair of radiation damage, an increased number of clonogens per unit of volume, a high hypoxic fraction, high [GSH] concentration, and rapid proliferation between fractions. In the present study, we evaluate the intrinsic radiation sensitivity (surviving fraction at 2 Gy or mean inactivation dose) of malignant human glioma cells in vitro. The in vitro radiation sensitivity of 21 malignant glioma cell lines (early and long term passages) has been measured using colony formation as the end-point of cell viability. The survival curve parameters (SF2 measured and calculated, alpha, beta, D0, n and MID) have been determined for single dose irradiations of exponential phase cells (18-24 hr after plating) under aerobic conditions and growing on plastic. The mean SF2 of the 21 cell lines is 0.51 +/- 0.14 (with a range of 0.19 to 0.76). This value may be compared to the mean SF2 of 0.43-0.47 for SCC, 0.43 for melanoma, and 0.52 for glioblastoma as reported from other authors when using colony formation of cells in exponential phase on plastic. Although glioblastoma is almost invariably fatal, our data demonstrate a very wide range of intrinsic radiosensitivities. These broadly overlap the radiation sensitivities of cell lines from tumors that are often treated successfully. We conclude that standard in vitro measurements of cellular radiation sensitivity (SF2) do not yield values that track in a simple manner with local control probability at the clinical level and that, for at least some of the tumors, other parameters and/or physiological factors are more important.

Cell Survival↗
PubMed1991

The importance of optimal treatment planning in radiation therapy.

There are two classes of failure in radiation therapy: local control not achieved and radiation-induced morbidity. Technical developments which permit the employment of treatment volumes which achieve a closer approximation to the target volume can confidently be asserted to yield clinical gains in terms of higher tumor control rates and/or reduced severity/frequency of radiation induced morbidity. The magnitude of the gains and the cost and effort to realize those gains may need to be assessed by the technique of the "clinical trial." Such gains will be the consequence of a higher dose to the target and/or the irradiation of smaller volumes of non-target tissues. An important fact is that unirradiated tissues do not develop radiation-related injury. Selected categories of radiation injuries that appear in non-target tissues are here reviewed. Valuable advances in the technology of radiation therapy are virtually certain for the near term. This bodes well, indeed, for our future patients.

Dose-Response Relationship, Drug↗
PubMed1990

Considerations in fractionated proton radiation therapy: clinical potential and results.

Protons have a finite range in tissue and can provide a better concentration of radiation dose in the tumor than conventional X-rays in certain situations. The development of optimized treatment plans for X-rays and protons followed by a comparative evaluation is one method of selecting tumor sites best suited for proton treatment. The preliminary results of comparative treatment planning for base of skull tumors and carcinoma of the prostate are discussed. These comparisons suggest a clinical gain for proton treatment of tumors in these locations. The clinical experience with fractionated proton treatment of several tumor sites is also discussed. The results of high dose proton treatment of chordomas and low grade chondrosarcomas of the base of skull is particularly promising: an actuarial 5-year local control of 78% has been obtained in 50 patients followed for a minimum of 22 months.

Carcinoma↗
PubMed1988

Estimation of tumor oxygenation and metabolic rate using 31P MRS: correlation of longitudinal relaxation with tumor growth rate and DNA synthesis.

31P MRS longitudinal relaxation times (T1) were determined for C3H murine fibrosarcomas (FSaII), and mammary carcinomas (MCaIV). Tumors were implanted in the foot dorsum, and were 100-300 mm3 in volume. T1s were repeated after the animal was allowed to breathe 100% oxygen for 30 min and then again 36-48 hr following 30 Gy. The spectrum were obtained using an 8.5 T spectrometer with a 8 cm bore and a 1.4 cm single turn antenna coil. The 31P relaxation times for untreated tumors in air breathing animals were: 3.78 sec for phosphomonoesters, 4.37 sec for inorganic phosphate (Pi), 2.73 sec for phosphocreatine, 1.37 sec for gamma ATP, 1.14 sec for alpha ATP, and 1.18 sec for beta ATP. The Pi T1s were 4.37 and 4.70 sec in control and irradiated tumors in air breathing animals. Respiration of oxygen for 30 min reduced the T1s to 3.02 and 2.62 sec in control and irradiated tumors respectively. The Pi T1 of an anoxic tumor, determined on an in situ tumor 60 min after death was 5.93 sec. The oxygen breathing induced decrease in the T1 of Pi is unlikely to have been caused by the paramagnetic properties of oxygen alone, and suggests a component of increased magnetization transfer secondary to the ATPase reaction. Oxygen breathing following 30 Gy, resulted in a decreased growth time (800 mm3 endpoint) and an increased proportion of cells in S-phase. These results support the hypothesis that the decrease in Pi T1 measured with oxygen breathing is a measure of tumor oxygen tension and metabolic rate, and suggests that T1 measurement may indirectly predict tumor growth rate and DNA synthesis.

Animals↗
PubMed1987

Size dependent changes in tumor phosphate metabolism after radiation therapy as detected by 31P NMR spectroscopy.

In Vivo 31P NMR spectroscopy was used to study changes in phosphate metabolism that occur after irradiation of the C3H fibrosarcoma, FSaII. Previously, we have shown that small FSaII tumors (less than 250 mm3) have a greater phosphocreatinine/inorganic phosphate (PCr/Pi) ratio and a lower hypoxic cell fraction (HCF) than large FSaII tumors (greater than 250 mm3). Six small tumors (113 +/- 26 mm3) were treated with radiation doses chosen to induce local control in greater than 50% of animals, (70-100 Gy, single fraction). Minimal changes in the tumor 31P NMR spectrum were seen over eight days of monitoring. During this interval, tumor regression began a minimum of 36 hours after radiation. This contrasted with large tumors (650-1000 mm3) wherein a significant increase in the Pcr/Pi ratio was seen 44 hr after irradiation. In tumors of this size range, a tumor growth delay of 4 to 7 days is obtained after a single 70 Gy fraction of radiation. Since small FSaII tumors have a minimal HCF (approximately equal to 4%), radiation induced reoxygenation would not be expected to have a large effect on their average cellular metabolism. Large tumors of this histology have a high HCF (greater than or equal to 40%), and may therefore be expected to have a significant average change in tumor cell metabolism with reoxygenation. The 31P NMR observations of small and large tumors after irradiation are compatible with radiation induced reoxygenation in the larger tumors.

Animals↗
PubMed1987

Effects of oxygen on the metabolism of murine tumors using in vivo phosphorus-31 NMR.

The effect of 100% inspired oxygen on in vivo tumor metabolism was examined using phosphorus-31 (31P) NMR spectroscopy. Isotransplants of two murine tumor histologies, designated MCaIV (C3H mammary adenocarcinoma) and FSaII (C3H fibrosarcoma), were used in syngeneic mice. Tumor volumes ranged from 30 to 1,800 mm3. Both tumor histologies are known to have a high hypoxic cell fraction when tumor volumes exceed 250 mm3. 31P nuclear magnetic resonance (NMR) spectra were obtained at 145.587 MHz, and the signal was detected using a 1.4 cm diameter, single loop coil designed to localize the signal from only the tumor. Spectral parameters for optimal signal-to-noise ratio (SNR) included a 60 degrees pulse and a 2-second recycle delay. Tumors were implanted in the hindfoot dorsum to assure that all detected mobile phosphates were of tumor origin. Phosphocreatine/inorganic phosphate (PCr/Pi) ratios of large tumors (greater than 250 mm3) were reduced compared with small tumors (less than 250 mm3) of the same histology. The increased PCr/Pi response to 100% inspired oxygen was greater for large tumors and for tumors with lower baseline PCr/Pi ratios. When host animals were given 10% oxygen for respiration, there was an increase in Pi and a decrease in both PCr and ATP. The response to 10% oxygen was observed in both large and small tumors of both tumor histologies studied. Resting skeletal muscle exhibited no alteration in the NMR spectrum during either 100 or 10% oxygen breathing. We conclude that the fractional increase in PCr/Pi ratio that occurs after 100% oxygen breathing is a sensitive, noninvasive method of detecting tumor hypoxia.

Animals↗
PubMed1987

[Fractionated proton radiotherapy].

Investigations in proton beam therapy of cancer patients have been initiated at the Cyclotron Laboratory, Harvard University, Cambridge, USA, since 1974 using a proton beam with the energy of 160 MeV for fractionated irradiation of uveal melanoma (899 cases), chordoma and chondrosarcoma of the base of the skull (96), sarcoma of the soft tissues and bones (79), prostatic cancer, head and neck tumors, etc. (altogether 1331 patients had been irradiated by June, 1986). To stop a beam in the target computer-assisted three-dimensional design and heterogeneity calculations were performed; computed compensatory boles were produced. Proton beam therapy is used alone or in combination with proton beam irradiation, routine radiotherapy. Areas of particular interest are ocular melanoma, chordoma and chondrosarcoma of the base of the skull, paraspinal sarcomas. Investigations in the field of proton beam therapy of malignant meningioma, metastases to the paraaortic lymph nodes hold promise.

Humans↗
PubMed1985

Selection bias in clinical trials.

Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.

Clinical Trials as Topic↗
PubMed1984

Preliminary results of a randomized trial of adjuvant doxorubicin for sarcomas: lack of apparent difference between treatment groups.

Forty-two patients with localized intermediate and high-grade sarcoma were randomized after optimal primary treatment to receive five cycles of adjuvant doxorubicin 90 mg/m2 every three weeks (20 patients) or observation (22 patients). Patients were stratified for grade, size, extent of surgical margin, and soft tissue versus other sarcomas. Groups appeared balanced for histology and superficial versus deep lesions. Eight patients (19%) have died. Follow-up times range from two to 69 months (median, 16 months). Two patients receiving doxorubicin (10%) developed cardiotoxicity presenting as pulmonary edema. One patient returned to normal activity on digoxin and diuretics; the other (age, 28 years) died of intractable failure and arrhythmias after four weeks. While a nonsignificant difference in local control, metastasis-free survival, disease-free survival, and survival was observed for extremity lesions, the advantage may be outweighed by the risk of cardiotoxicity. Seventy-six percent of the control patients with extremity lesions remain disease free. Because control patients do well, a very large study is required to define the role of adjuvant doxorubicin.

Adult↗
PubMed1982

Proton beam irradiation of uveal melanomas. Results of 5 1/2-year study.

Proton beam irradiation was used in the treatment of 76 uveal melanomas from July 1975 to December 1980. Five (7%) were small, 32 (42%) were medium, and 39 (51%) were large melanomas. The follow-up period ranged from two months to 5 1/2 years; 19 patients were followed up for more than two years and 39 were observed for more than a year. Tumor regression has been achieved in all eyes with more than 12 months of follow-up except one, which was enucleated because of secondary complications. Three patients in whom metastatic disease developed died. Our data indicate that proton irradiation can be used for the treatment of relatively large lesions that previously were considered untreatable and reduces the high ocular morbidity experienced with other methods in the treatment of medium and small melanomas.

Adult↗
PubMed1982

Evaluation of the clinical applicability of proton beams in definitive fractionated radiation therapy.

We report on the treatment of 317 patients treated either wholly or in part with proton beams at the Harvard Cyclotron Laboratory. These include: 130 patients treated for definitive radiation therapy of choroidal melanoma; 17 patients treated for tumors of the base of skull, cervical spine and cranium, which abut structures of the central nervous system (CNS); 23 patients treated for sarcomas of soft tissue and bone; 65 patients treated for carcinoma of the prostate; 14 patients treated for carcinoma of the rectum and anus; and 23 patients treated for squamous carcinoma of the oral cavity and oro-pharynx. Data on causes of failure and morbidity of treatment are presented. Overall the results are judged to be extremely encouraging. In particular, the treatment of the choroidal melanomas and sarcomas abutting CNS structures have clear clinical value, and the treatment of prostatic tumors and tumors of the head and neck are thought to be promising.

Bone Neoplasms↗
PubMed1978

Enhancement by Corynebacterium parvum of the normal and tumor tissue response to hyperthermia.

The effect of Corynebacterium parvum treatment on the response of tumor and normal tissue to hyperthermia (43.5 degrees) was studied. Animals were C3Hf/Sed mice from our defined flora mouse colony. The time at hyperthermia that achieved control of one-half of methylcholanthrene-induced fibrosarcomas and the foot reaction were examined after treatment. C. parvum, if given 3 to 32 days before hyperthermia, enhanced the reaction to local hyperthermia of normal tissue. No enhancement was observed if C. parvum was given after hyperthermia. This enhancement was more dramatic for tumor response resulting in a therapeutic gain factor of congruent to 2.3 (3.7/1.6). Comparative studies on combined Corynebacterium and radiation failed to demonstrate the enhancement to normal tissue.

Animals↗