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Biomedical subjects

K K Fu

Publications and source records attributed to K K Fu.

At least 55 records · Page 3Linked to original sources
PubMed1995

Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation.

PURPOSE: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. METHODS AND MATERIALS: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). RESULTS: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or bone-equivalent phantom. CONCLUSIONS: The impact of radiation therapy on plate preservation after mandibular reconstructive surgery using a titanium plate may be dependent on the timing of RT relative to surgery. Significantly more mandibular reconstruction plates were lost when the involved mandible received RT in the perioperative period than when RT was delivered beyond 10 months from surgery or when no RT was given. The use of alloplastic implants such as titanium plates in conjunction with myocutaneous flap coverage for mandibular reconstruction is attractive because it allows immediate reconstruction of the defect and promotes a good functional and cosmetic result; however, administration of perioperative RT may result in a higher plate failure rate.

Adolescent↗
PubMed1995

Randomized phase I/II trial of two variants of accelerated fractionated radiotherapy regimens for advanced head and neck cancer: results of RTOG 88-09.

PURPOSE: To establish the feasibility of performing split-course accelerated hyperfractionation (AHFX-S) and concomitant boost accelerated fractionation radiotherapy (AFX-C) for advanced head and neck cancer in a multi-institutional cooperative trial setting and to evaluate the tumor clearance rate and acute and late toxicity of these fractionation schedules. METHODS AND MATERIALS: Between February 1989 and January 1990, 75 patients with Stage III or IV squamous cell carcinoma of the head and neck were randomized to receive: (a) AHFX-S: 1.6 Gy/fraction, twice daily (6-h interval), 5 days/week, to a total dose of 67.2 Gy/42 fractions/6 weeks, with a 2-week rest after 38.4 Gy; or (b) AFX-C: 1.8 Gy/fraction/day, 5 daily fractions/week to 54 Gy/30 fractions/6 weeks to a large field and 1.5 Gy/fraction/day to a boost field, 6 h after large field treatment during the last 11 treatment days, to a total dose of 70.5 Gy/41 fractions/6 weeks. Acute and late toxicities were scored according to the RTOG normal tissue reaction scales and tumor clearance was evaluated at completion of therapy and at regular intervals thereafter. RESULTS: Of the 70 analyzable patients, 38 received AHFX-S and 32 received AFX-C. The two arms were balanced with respect to sex, age, T-stage, and Karnofsky Performance Status (KPS). However, the AHFX-S arm had a higher proportion of oropharyngeal primaries (63% vs. 44%), and Stage IV disease (82% vs. 50%) and lower proportion of oral cavity lesions (3% vs. 22%) and N0 disease (16% vs. 31%) than the AFX-C arm. The median follow-up was 2 years (range: 0.03-4.87 years). Tolerance of both variants of accelerated fractionated radiotherapy was satisfactory. There was no significant difference in local-regional control, disease-free survival, or survival between the two arms. The 2-year local-regional failure rate, survival, and disease-free survival was 50, 50, and 40%, respectively, for the entire group of patients. Acute radiation mucositis was increased in both arms. There was no significant difference in the incidence of grade 3 acute toxicities (63% vs. 56%) and grade 3 (14% vs. 14%) or grade 4 (6% vs. 17%) late toxicities. Permanent grade 4 late toxicity was observed in 6 and 7% of the patients, respectively. CONCLUSION: Results of this randomized Phase I/II trial showed that the two accelerated fractionated schedules studied can be successfully given in a multi-institutional cooperative trial. There was no significant difference in acute or late toxicities, local-regional control, disease-free survival, or survival in this small scale study. Therefore, a Phase III trial comparing the relative efficacy of these two accelerated fractionation schedules against standard fractionation and hyperfractionation has been activated.

Carcinoma, Squamous Cell↗
PubMed1995

Late effects of hyperfractionated radiotherapy for advanced head and neck cancer: long-term follow-up results of RTOG 83-13.

PURPOSE: The objective of this study was to examine the incidence of late effects of hyperfractionated radiotherapy for head and neck cancer as a function of the dose delivered, as well as the daily interfraction interval. In addition, we wished to examine the influence of other prognostic factors including age, gender, primary site, T- and N-stage, and overall stage on the late effects of hyperfractionated radiotherapy. METHODS AND MATERIALS: Between 1983 and 1987, 479 patients with advanced head and neck cancer were entered on a Phase ILE/II dose escalation trial of hyperfractionated radiotherapy. They were randomly assigned to receive a dose of 67.2, 72.0, 76.8, or 81.6 Gy, delivered at 1.2 Gy/fraction, twice a day (BID), 5 days/week. Of the 451 analyzable patients, 399 patients who received > or = 64.8 Gy and had a follow-up > 90 days were eligible for this study. Acute and late effects were scored with the RTOG/EORTC late radiation morbidity scoring scheme. For this analysis, patients were subclassified by the actual doses delivered and by an average daily interfraction interval of < or = 4.5 h or > 4.5 h. The incidence of late effects was estimated using a cumulative incidence approach. RESULTS: Fifty-nine patients received 67.2 +/- 2.4 Gy, 119 received 72.0 +/- 2.4 Gy, 98 received 76.8 +/- 2.4 Gy, and 123 received 81.6 +/- 2.4 Gy. The proportion of patients treated with a daily interfraction interval of > 4.5 h was 32, 50, 43, and 71%, respectively. The four treatment groups were well balanced with respect to pretreatment characteristics. The median follow-up was 1.71 years (range: 0.24-9.6) for all evaluable patients and 6.12 years for 85 alive patients. There was no significant difference in the incidence of late effects between the different dose levels. At 5 years, the cumulative incidence of late effects was 17, 14, 20, and 13% for grade 3, and 7, 3, 7, and 5% for grade 4. However, the incidence of late effects differed significantly with respect to daily interfraction interval. The cumulative incidence of grade 4 late effects increased from 6.3% at 2 years to 7.5% at 3 years to 8.0% at 4 years and 8.6% at 5 years with an interval of < or = 4.5 h, while it remained at a constant of 2.0% with an interval of > 4.5 h during the same period (p = 0.0036). Multivariate analysis showed that among the prognostic factors examined, daily interfraction interval of < or = 4.5 h was the only significant independent prognostic factor for the development of grade 3+ or grade 4 late effects (p = 0.0167 and p = 0.0013, respectively). CONCLUSION: Results of this randomized Phase ILE/II trial of hyperfractionated radiotherapy in head and neck cancer showed no apparent dose-response relationship for late effects within the range of 67.2-81.6 Gy. Daily interfraction interval was a significant independent factor for the development of late effects in a multivariate analysis.

Adult↗
PubMed1995

Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas.

PURPOSE: The objectives of this study were to determine the efficacy and toxicity of Etanidazole (ETA), a hypoxic cell sensitizer, when combined with conventional radiotherapy (RT) in the management of advanced head and neck carcinomas. METHODS AND MATERIALS: From March 1988 to September 1991, 521 patients who had Stage III or IV head and neck carcinomas were randomized to receive conventional RT alone (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 fractions per week) or RT+ETA (2.0 g/m2 thrice weekly for 17 doses), of whom 504 were eligible and analyzable. Treatment assignments were stratified before randomization according to the primary site (oral cavity + hypopharynx vs. supraglottic larynx + oropharynx + nasopharynx), T-stage (T1-3 vs. T4), and N-stage (N0-2 vs. N3). Pretreatment characteristics were balanced. In the RT-alone arm, 39% of patients had T3 and 34% had T4 disease, whereas in the RT+ETA arm, 42% of patients had T3 and 33% had T4 disease. Thirty-eight percent of the RT-alone patients and 37% of the RT+ETA patients had N3 disease. The median follow-up of surviving patients was 3.38 years, with a range between 0.96 and 5.63 years. RESULTS: One hundred and ninety-four of the 252 (77%) RT+ETA patients received at least 14 doses of the drug. Overall RT protocol compliance rate was 82% in the RT-alone arm and 86% in the RT+ETA arm. No Grade 3 or 4 central nervous system or peripheral neuropathy was observed in the RT+ETA arm. Eighteen percent of the patients developed Grade 1 and 5% developed Grade 2 peripheral neuropathy. Other drug related toxicities included nausea/vomiting (27%), low blood counts (15%), and allergy (9%). Most of these toxicities were Grade 1 and 2. The incidence of severe acute and late radiation effects were similar between the two arms. The 2-year actuarial local-regional control rate (LCR) was 40% for the RT-alone arm and 40% for the RT+ETA arm. Two-year actuarial survival was 41% for the RT-alone arm and 43% for the RT+ETA arm (p = 0.65). Multivariate analyses were performed to investigate the influence of covariates on treatment effects. A strong treatment interaction with N-stage was revealed: LCR (50% vs. 40% at 2 years), RT+ETA improved for patients with N0-2 disease but not for N3 patients (22% for RT+ETA and 40% for RT). Further analyses showed that RT+ETA was more advantageous in N0-1 patients, with a 2-year LCR of 55% for RT+ETA vs. 37% for RT only (p = 0.03). A similar phenomenon was observed when using survival as the end point. CONCLUSION: The results showed that adding Etanidazole to conventional RT produced no global benefit for patients who had advanced head and neck carcinomas. There was a suggested benefit for patients who had N0-1 disease, and that needs to be confirmed by another study.

Carcinoma, Squamous Cell↗
PubMed1995

An experimental model to determine the effect of irradiated tissue on neutrophil function.

Complications of irradiated tissue include infections and impaired healing. Although fibrosis and hypovascularity contribute, a cellular mechanism has not been identified. This study examines the effect of radiation (10 to 30 Gy) on neutrophil function in a rabbit wound cylinder model. At 3 to 12 weeks after radiation, subcutaneous wound cylinders were implanted in both irradiated and control fields in 19 rabbits. Wound neutrophils were subsequently assayed for phagocytosis (3H-labeled Staphylococcus aureus assay), superoxide production (cytochrome c reduction assay), and surface Mac-1 expression (flow cytometric assay using MHM 23 monoclonal antibody). Phagocytosis of 3H-labeled S. aureus was significantly lower in neutrophils from irradiated fields compared with controls at 6 and 12 weeks after radiation (6.5 versus 18.9 bacteria per neutrophil at 12 weeks; p = 0.027). Stimulated neutrophils from irradiated tissue could not increase superoxide production or Mac-1 expression as much as controls, with differences increasing as postirradiation time increased. The diminished phagocytosis, superoxide production, and Mac-1 expression provide a cellular mechanism that may account for susceptibility to infection and poor healing in irradiated tissues.

Animals↗
PubMed1995

Cisplatin neuropathy: a prospective clinical and electrophysiological study in Chinese patients with ovarian carcinoma.

Nineteen Chinese patients with stage III or IV epithelial ovarian carcinoma by the criteria established by the International Federation of Gynaecology and Obstetrics, treated with cisplatin, 120 mg/m2, every 4 weeks for a maximum of twelve courses if possible, were studied prospectively with clinical and electrophysiological evaluation before and 3, 6, 9 and 12 months during cisplatin administration. Neuropathy occurred in 12 of the 19 patients at the cumulative dose of 360 mg/m2. Up to 89% of the patients assessed in their final examination developed neuropathy. Decreased vibration sensation at the ankles and depressed ankle reflexes were the early manifestations. Electrophysiological findings consisted of low amplitude sensory action potentials of median, ulnar and sural nerves, and slowing of their sensory nerve conduction velocities. Despite substantial involvement of sensory nerves, there was little change in motor nerve conduction velocities or motor unit action potentials. The progression of the neuropathy was unpredictable and could be delayed. As cisplatin is highly effective in the treatment of the tumour which is invariably fatal, if inadequately treated, patient selection with regard to neurotoxicity is unnecessary.

Action Potentials↗
PubMed1994

Flow cytometric quantification of the proliferation-associated nuclear antigen p105 and DNA content in advanced head & neck cancers: results of RTOG 91-08.

PURPOSE: p105 is a proliferation-associated nuclear antigen which identifies proliferating but not resting cells. The objectives of this Radiation Therapy Oncology Group (RTOG) protocol (91-08) were: (1) to correlate tumor proliferative potential estimated using the p105 assay and deoxyribonucleic acid (DNA) analysis with treatment outcome in patients irradiated for advanced squamous cell carcinoma of the head and neck; and (2) to evaluate the potential of p105 labeling indices as a predictive assay. METHODS AND MATERIALS: Paraffin blocks of pretreatment biopsies of the primary tumor or metastatic neck nodes of patients with Stage III or IV squamous cell carcinoma of the head and neck treated with radiotherapy alone in three previous RTOG protocols (79-13, 79-15, and 83-13) were retrospectively obtained. From these paraffin blocks, areas of tumor were selected based on histological examinations and sectioned. Nuclei suspensions were then prepared and processed for p105 antibody and DNA staining and subsequent flow cytometric quantification of p105 labeling indices and DNA content and correlation with local-regional control and survival. RESULTS: Paraffin blocks of tumor biopsies from 148 out of a total of 598 eligible patients were available. Of these, 143 were analyzable. The median and (range) of p105 labeling index (LI-C), p105 labeling index of cells in S phase (LI-S), and p105 antigen density (AD) were: 66.6 (3.85-99.5), 9 (1.55-36), and 93.2 (7.4-628.5), respectively. Deoxyribonucleic acid was diploid in 67 (47%), aneuploid in 22 (15%) and mixed aneuploid/diploid in 54 (38%) patients. There was a strong correlation between AD and DNA ploidy. Antigen density was above median in 91.5% of the aneuploid or mixed aneuploid/diploid tumors, but only in 8.5% of the diploid tumors. Patients with aneuploid or mixed aneuploid/diploid tumors had significantly greater local-regional failures than patients with diploid tumors (p = .0180). Those with p105 LI-C below the median or p105 AD above the median also had significantly greater local-regional failures (p = .0500 and p = .0167, respectively). Patients with p105 AD below the median had significantly better survival than those above the median (p = .0444), although there was no significant difference in survival with respect to DNA ploidy or p105 LI-C. Multivariate analyses showed that T-stage (p = .0001) and p105 AD (p = .0044) were significant prognostic factors for local-regional control, and T-stage (p = .0080), N-stage (p = .0021), primary site (p = .0110), and p105 AD (p = .0326) were significant prognostic factors for survival. CONCLUSION: These results suggest that flow cytometric quantitation of the proliferation-associated nuclear antigen p105 and DNA content of pretreatment tumor biopsies may be a potentially useful predictive assay in patients irradiated for advanced squamous cell carcinomas of the head and neck.

Analysis of Variance↗
PubMed1993

Lack of effect of supplemental dietary selenium on time to development of radiation-induced cutaneous tumors in rats.

Sprague-Dawley 8-week-old male rats received a single dose of 1425 cGy to the skin of the back using a 6 meV electron beam. Three days later they were randomized into three groups receiving supplemental dietary selenium as sodium selenite at levels of 0 ppm, 1 ppm, and 2 ppm selenium. Cutaneous tumors first appeared 33 weeks after irradiation and the experiment was terminated at 63 weeks. A wide variety of epithelial and connective tissue tumors developed. There was no significant difference in the time to development of epithelial or connective tissue tumors between the three groups. Thus, under the conditions of this experiment an inhibitory effect of dietary selenium on radiation-induced skin tumors was not evident.

Animals↗
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↗