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K K Fu

Publications and source records attributed to K K Fu.

At least 19 recordsLinked to original sources
PubMed1992

Interruptions adversely affect local control and survival with hyperfractionated radiation therapy of carcinomas of the upper respiratory and digestive tracts. New evidence for accelerated proliferation from Radiation Therapy Oncology Group Protocol 8313.

Hyperfractionated radiation therapy (HFX) attempts to overcome tumor proliferation during treatment by permitting higher total doses in the same overall time as standard fractionation. Whereas interruptions, including splits, reduce local control with standard fractionation in carcinoma of the upper respiratory and digestive tracts, HFX might compensate for interruptions. Patients were randomized to receive total doses of 6720, 7200, 7680, and 8160 cGy, using 120 cGy twice daily, 5 days per week. Those analyzed received +/- 4% of assigned total dose and lived 90 days or more. Treatment was completed within 5 days of the time specified for each treatment arm in 233 patients; 48, 80, and 131 patients had delays 14, 10, and 5 days or more, respectively. Locoregional control and survival were significantly (P less than or equal to 0.03) reduced with delays of 5 days or more when corrected for prognostic factors. Late effects of radiation therapy were not affected by interruptions. These data support the hypothesis that proliferation (possibly accelerated) of tumor clonogens during treatment influences the outcome.

Aged↗
PubMed1992

Correlations between in vivo 31P MRS measurements, tumor size, cell survival, and hypoxic fraction in the murine EMT6 tumor.

Phosphorus metabolite ratios were measured using 31P magnetic resonance spectroscopy shortly before measurement of cell survival and radiobiologic hypoxic fraction (HF) in EMT6/SF tumors, transplanted into a hindlimb of Balb/c mice. A total of 58 tumors with a volume range of 180 to 1250 mm3 were examined in experiments entailing no anesthesia. Postirradiation tumor cell viability was measured using an in vitro clonogenic assay. Correlations between tumor volume, surviving fraction (SF), HF, phosphorus metabolite ratios, and intracellular pH were computed. Both SF and HF increased significantly with tumor volume as did the metabolite ratios of inorganic phosphorus and phosphomonoesters to nucleoside triphosphates (Pi/NTP and PME/NTP, respectively), as well as Pi to phosphocreatine (Pi/PCr). In comparison to HF, the ratios of Pi/NTP, Pi/PCr, and PME/NTP each yielded significant positive correlations (Kendall correlation coefficients(tau) = 0.25 to 0.33). However, these were not significantly stronger than the correlation between HF and volume (tau = 0.21). Apparent values of tumor pH did not correlate with any other measured parameter. While these results indicate a statistical relationship between HF and the measured metabolite ratios, the widely scattered data, as reflected by magnitude of tau less than 0.35, made metabolite ratios poor predictors of HF in individual tumors.

Animals↗
PubMed1991

5-year results of cisplatin and fluorouracil infusion in head and neck cancer.

As part of the developmental process for the Head and Neck Intergroup trial of adjuvant chemotherapy for advanced resectable head and neck carcinoma, in 1981 the Radiation Therapy Oncology Group, Philadelphia, Pa, conducted two nonrandomized pilot studies using chemotherapy consisting of three courses of cisplatin and fluorouracil infusion. Chemotherapy was administered prior to surgery in 42 patients (induction) and after surgery in an additional 29 patients (sequential). The populations were roughly comparable with respect to tumor site and stage. Twelve of the 42 patients in the induction group and seven of the 29 in the sequential group are alive and with no evidence of disease at the last reported follow-up. The median survival was 31 months in the sequential group vs 20 months in the induction group. Only two of the 26 patients with less than a complete clinical response following induction chemotherapy are still alive. Twenty-seven of the 42 patients who received induction chemotherapy did not undergo surgery as initially planned. Despite the lack of surgery, at 5 years the survival between the two groups was not significantly different (27% for the induction group vs 23% for the sequential group).

Adult↗
PubMed1991

Early and late effects of cisplatin and radiation at acute and low dose rates on the mouse skin and soft tissues of the leg.

The influence of radiation dose rate and drug dose on the combined effects of cisplatin (Cis-diamminedichloroplatinum (II] and radiation on the skin and soft tissues was studied in the C3Hf/SED mice. Localized acute-dose-rate irradiation (ADRI) at 3.345 Gy/min and continuous low-dose-rate irradiation (CLDRI) of the hind leg at 0.028 Gy/min with and without the drug was delivered using a 137Cs laboratory irradiator. Cisplatin at 6 or 11 mg/kg was given by intraperitoneal bolus injection 1 hour before ADRI or by continuous infusion during CLDRI. Acute skin reaction was scored from days 13 to 30 and late skin contraction and leg contracture were measured at days 90, 180, 270, and 360 after treatment. A marked dose-rate effect was observed for these early and late normal tissue endpoints. At a dose of 60 Gy of CLDRI, the dose rate factor (DRF = isoeffect dose at CLDRI/isoeffect dose at ADRI) was 1.82 for acute skin reaction and 1.76 for late skin contraction or leg contracture at day 270. However, there was no significant enhancement of these early and late normal tissue effects by cisplatin at 6 or 11 mg/kg at either acute or low dose rates. Thus neither drug dose nor radiation dose rate had a significant impact on the combined effects of cisplatin and radiation on the mouse skin and soft tissues of the leg.

Animals↗
PubMed1991

ASTRO plenary: interfraction interval is a major determinant of late effects, with hyperfractionated radiation therapy of carcinomas of upper respiratory and digestive tracts: results from Radiation Therapy Oncology Group protocol 8313.

A prospective, randomized, multi-institutional, Phase I(LE)/II trial of HFX was conducted by the RTOG between 1983 and 1987. Patients with histologically proven, inoperable squamous cell carcinoma of the upper respiratory and digestive tracts stratified by site, nodal status, and performance status, were assigned to one of three arms, were assigned to one of three arms, 67.2 Gy, 72.0 Gy, or 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week: intervals of 4 to 8 hours were permitted between fractions. After acceptable rates of acute normal tissue effects were found, the randomization was changed to evaluate a new higher total dose, 81.6 Gy. Of 479 patients entered, 447 were analyzed, 63 on 67.2 Gy, 129 on 72.0 Gy, 117 on 76.8 Gy, and 138 on 81.6 Gy. The treatment arms were well balanced with respect to pretreatment characteristics. Acute reactions consisted almost entirely of pseudomembranous inflammation. "Severe" (Grade 3) acute reactions were reported in 33% to 41% and grade 4 reactions were found in 0 to 3% of patients, with no differences in frequencies among the four arms. Toxicities that developed or persisted beyond 90 days after the first treatment (408 patients evaluable greater than 90 days) did not differ among arms: grade 3+ reactions occurred in 10% to 14%, and grade 4+ effects (necroses) were reported in 5% at 67.2 Gy, 3% at 72.0 Gy, 7% at 76.8 Gy, and 2% at 81.6 Gy. Grade 3+ acute reactions occurred in 40% of patients when the interfraction interval was less than or equal to 4.5 hours versus 31% with greater than 4.5 hours (p = .03). Interfraction intervals less than or equal to 4.5 hours were associated with higher frequencies of grade 4+ late effects in all four arms, 8% of 197 patients with less than or equal to 4.5 hours versus 1% of 211 patients with greater than 4.5 hours. Estimates of late toxicity at 1, 2, and 3 years were 5.5%, 9.8%, and 15.4% with intervals less than or equal to 4.5 hours, versus 1.7% at all three periods for greater than 4.5 hours (p = .006). Local-regional control at 2 years was 25% for the assigned dose of 67.2 Gy compared to 43% to 45% for the three higher doses (p = .01), but a similar comparison for survival showed no significant difference (p = .35). There was no evidence for an effect of interfraction interval on either local-regional control (p = .38) or survival (p = .28).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Early and late effects of mitomycin C and continuous low-dose-rate irradiation on the mouse skin and soft tissues of the leg.

The early and late effects of combined mitomycin C and continuous low-dose-rate irradiation (CLDRI) on the skin and soft tissues were studied in the C3Hf/SED mice. Localized CLDRI of the hind leg at 0.028 Gy/min with and without mitomycin C was delivered using a 137Cs laboratory irradiator. Mitomycin C at 6 mg/kg was given by continuous infusion through intraperitoneally implanted osmotic mini-pumps during CLDRI. Acute skin reaction was scored from days 13 to 30 and late skin contraction and leg contracture were measured at days 90, 180, 270, and 360 after treatment. Mitomycin C increased the early skin reaction following CLDRI; at a dose of 60 Gy, the dose effect factor was approximately 1.1. However, there was no significant enhancement of late skin contraction or leg contracture by mitomycin C. Our results suggest that mitomycin C can be combined with low-dose-rate brachytherapy without a significant increase in early or late damage to the skin and soft tissues.

Acute-Phase Reaction↗
PubMed1991

Biologic rationale of combined radiotherapy and chemotherapy.

This article presents a brief review of the mechanisms by which chemotherapy can be combined with radiotherapy to improve the therapeutic ratio, the possible mechanisms of interaction between chemotherapy and radiotherapy, the various factors that may influence their combined effects, and future perspectives in this area of clinical and laboratory research.

Animals↗
PubMed1990

Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of radiation therapy oncology group protocol 83-13.

A prospective, randomized Phase Ilate/II trial of hyperfractionated radiation therapy was conducted: 1.2 Gy minimum tumor dose was administered twice daily with a minimum interval of 4 hr, 5 days per week. Patients with Stage III and IV carcinomas of the oral cavity, oropharynx, nasopharynx, hypopharynx, and supraglottic larynx were stratified by site, presence or absence of nodal metastases, and performance status. They were assigned to four total doses between 67.2 Gy and 81.6 Gy to all known tumors. The highest dose arm was opened after preliminary assessment indicated acceptable late morbidity rates with the three lower doses. Of 479 patients entered, 260 patients were randomized to the three lower total doses and 237 were analyzed for this preliminary report: 63 were assigned to receive 67.2 Gy, 58 to 72.0 Gy, and 116 to 76.8 Gy. Estimates of grade 4 necrosis at 2 years were 10.0%, 5.1%, and 13.9%, respectively, for patients who received total doses of 67.2 Gy, 72.0 Gy, and 76.8 Gy. There was a suggestion of a trend toward increased local control at 24 months (Kaplan-Meier estimates of 25% for 67.2 Gy, 37% for 72.0 Gy, and 42% for 76.8 Gy) (p = .08). No difference was observed in survival. Assessment of the results using Cox regression models to correct for slight inequalities of pretreatment prognostic variables supported a total dose-tumor control relationship (p = .054). Results for the lowest dose arm were comparable to previous RTOG studies of common fractionation with similar total doses. The higher local control rates with 72.0 and 76.8 Gy using hyperfractionated radiation therapy suggest an improvement in outcome with radiation therapy for advanced carcinomas of the upper aerodigestive tracts. These preliminary findings have led to a Phase III comparison of hyperfractionated radiation therapy with 1.2 Gy b.i.d. with standard fractionation.

Adult↗
PubMed1990

Correlations between in vivo 31P NMR spectroscopy measurements, tumor size, hypoxic fraction and cell survival after radiotherapy.

Phosphorus metabolite levels were measured non-invasively using 31P magnetic resonance spectroscopy (MRS) in SCCVII/SF tumors, subcutaneously transplanted into the legs of unanesthetized C3Hf/Sed mice. Shortly after MRS measurements, tumors were irradiated with a single dose of 20 Gy, and cell survival and radiobiologic hypoxic fraction were determined with an in vitro cloning assay. Significant correlations were found between tumor size and surviving fraction, hypoxic fraction, pH, and phosphorus metabolite ratios. With increase of tumor size, surviving fraction and hypoxic fraction both increased, the ratios of inorganic phosphate and phosphomonoesters to nucleoside triphosphates (Pi/NTP and PME/NTP, respectively) and inorganic phosphate to phosphocreatine (Pi/PCr) increased and pH decreased. However, considerable heterogeneity of MRS spectral parameters, even in tumors of similar size, precluded accurate prediction of hypoxic fraction and cell survival after radiotherapy.

Animals↗
PubMed1990

High-dose-rate versus low-dose-rate intracavitary brachytherapy for carcinoma of the cervix.

High-dose-rate (HDR) remote afterloading intracavitary brachytherapy has been widely used in the treatment of carcinoma of the cervix in Europe and Asia since the 1960's. Recently, there has been an increase of interest in the use of this technique in North America. Most of the non-randomized studies suggest similar survival, local control, and complication rates using fractionated high-dose-rate remote afterloading intracavitary brachytherapy combined with external beam irradiation compared to historical or concurrent low-dose-rate (LDR) controls. However, the techniques as well as the dose fractionation schedules used in different institutions are variable. The optimal technique and dose fractionation scheme has yet to be established through systematic clinical trials.

Brachytherapy↗
PubMed1989

Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides.

Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived. Therapy was well tolerated. No significant hematological toxicity occurred. Although total body X ray irradiation and total skin electron beam radiotherapy produced excellent palliation of patients with advanced stage mycosis fungoides, new strategies to provide more effective systemic treatment are needed.

Adult↗
PubMed1988

Improved dose distribution with customized I-125 source loading in temporary interstitial implants.

I-125 sources are being used in temporary interstitial implants of various sites. Radiation safety considerations favor its use over other available radioisotopes. Cost containment is achieved by using the same sources for a number of patients. Loading I-125 seeds into implant catheters at our institutions permit customized source arrangement to optimize the implant dose patterns. Clinical examples are given for which the dose distributions achieved with customized source loading are superior to those achievable with standard Ir-192 ribbons.

Brachytherapy↗
PubMed1988

Brachytherapy.

Explore the source record for details and available documents.

Antineoplastic Agents↗
PubMed1988

Plasma and tumor concentrations of cisplatin following intraperitoneal infusion or bolus injection with or without continuous low-dose-rate irradiation.

Our purpose of this study was to determine whether whole-body, continuous low-dose-rate irradiation (CLDRI) alters the plasma and/or tumor platinum pharmacokinetics after ip bolus injection or ip infusion as a possible mechanism of interaction between CLDRI and cisplatin. The C3Hf/Sed mice bearing SCCVII/SF tumors were given 6 mg cisplatin/kg ip by bolus injection or an ip infusion of 0.25 mg cisplatin.kg-1.hour-1 for 48 hours with and without CLDRI at 0.56 Gy/hr for 24 or 48 hours. Plasma and tumor platinum concentrations were determined with an atomic absorption spectrophotometer at appropriate intervals during infusion and up to 48 hours after drug administration. Both total and ultrafilterable plasma platinum followed a biphasic elimination after ip bolus injection, whereas only a prolonged single-phase elimination was seen after ip infusion. Tumor uptake of platinum appeared to follow a passive diffusion pattern with a prolonged cellular retention of platinum. Whole-body CLDRI had no apparent effect on the pharmacokinetics of plasma and tumor platinum administered by ip bolus injection or prolonged continuous infusion.

Animals↗
PubMed1987

Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group.

Seventeen patients with advanced or recurrent salivary gland cancer were treated with cisplatin, doxorubicin, and 5-fluorouracil combination chemotherapy (PAF). Two patients achieved a complete response and four patients achieved a partial response, for an overall response rate of 35%. Six of the nine patients who received PAF in the neoadjuvant setting did not respond and proceeded to surgery and/or radiation therapy. No difference in response rate was found between those patients treated for recurrent disease v those treated with neoadjuvant chemotherapy. All three patients with adenocarcinoma responded. The response duration in patients with metastatic or recurrent disease ranged from 6 to 15 months. The PAF regimen was delivered primarily in the outpatient setting and was associated with acceptable toxicity. PAF demonstrates activity in salivary gland malignancies, and further evaluation of this combination seems warranted.

Adult↗
PubMed1987

Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial.

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.

Adult↗