PubMed Health⌕ Search

Biomedical subjects

W J Koh

Publications and source records attributed to W J Koh.

At least 37 records · Page 2Linked to original sources
PubMed1996

MR characterization of post-irradiation soft tissue edema.

OBJECTIVE: Radiation therapy is often used to treat bone und soft tissue neoplasms, and commonly results in soft tissue edema in the radiation field. However, the time course, distribution and degree of this edema have not been well characterized. Our study was carried out to better define these features of the edema seen following neutron and photon radiation therapy. DESIGN AND PATIENTS: Two hundred and twenty-six patients underwent radiation therapy as part of combined modality management for musculoskeletal sarcomas between 1985 and 1993. Of these, 15 had surgical resection of their neoplasm, had no clinical evidence of recurrent disease, and had adequate MR follow-up that allowed sequential assessment of soft tissue following irradiation. Ten patients received photons with an average dose of 52.8 Gy. Five patients received neutrons with an average dose of 17.3 nGy. Sequential MR follow-up was available in these patients for an average of 22.8 months following radiation therapy. On each of the serial MR imaging studies, subcutaneous fat, muscle, and the intramuscular septa/fascial planes were graded subjectively as to size and signal intensity. RESULTS: In general, soft tissue signal intensity in the radiation field initially increased over time, peaking at about 6 months for neutron-treated patients and at about 12-18 months for photon-treated patients. Signal intensity then decreased slowly over time. However, at the end of the follow-up period, signal intensity remained elevated for most patients in both groups. Signal intensity in a particular tissue was greater and tended to persist longer on STIR sequences than on T2-weighted sequences. Survival analysis of signal intensity demonstrated much longer edema survival times for neutron-treated patients than for photon-treated patients. Signal intensity increase in the intramuscular septa persisted for much longer than for fat or muscle. A mild increase in size was noted in the subcutaneous fat and intramuscular septa. Muscle, on the other hand, showed a decrease in size following treatment. This was mild for the photon-treated group and more marked for the neutron-treated group. CONCLUSIONS: There is a relatively wide variation in the duration and degree of post-irradiation edema in soft tissues. This edema seems to persist longer in the intramuscular septa than in fat or muscle. Although the duration of follow-up was limited, our study suggests that this edema resolves in roughly half the photon-treated patients within 2-3 years post-treatment and in less than 20% of neutron-treated patients by 3-4 years post-treatment. Muscle atrophy was seen in both photon- and neutron-treated patients, but was more severe in the neutron-treated group.

Adipose Tissue↗
PubMed1996

Clinical trials of neutron radiotherapy in the United States.

The development of clinical neutron facilities in the 1980s, capable of delivering high energy neutrons spurred full scale phase III testing of neutron beam radiotherapy in a number of tumors including salivary gland, head and neck, prostate, and non small-cell lung cancer. The Radiation Therapy Oncology Group (RTOG) and the Medical Research Council (MRC) jointly sponsored a randomized trial for the treatment of advanced stage salivary gland tumors comparing neutron to conventional photon and/or electron radiotherapy. Although no improvement in survival was seen, the study demonstrated a striking and statistically significant difference in the local-regional control of unresectable salivary gland tumors (56 vs 17%), favoring neutron beam irradiation. Subsequent clinical trials of neutron beam irradiation were initiated by the Neutron Therapy Collaborative Working Group (NTCWG) sponsored by the National Cancer Institute (NCI). A phase III trial comparing neutron to photon radiotherapy for inoperable regional non-small cell lung cancer showed no overall improvement in survival. However, a statistically significant improvement in survival was observed in the subset of patients with squamous cell histology. The NTCWG trial comparing fast-neutron therapy versus conventional photon irradiation in the treatment of advanced squamous cell carcinomas of the head and neck showed a statistically significant improvement in initial complete response (70 vs 52%) favoring neutrons. However, subsequent failures erased any difference in ultimate local-regional control rates and survival curves were essentially the same in both arms. The randomized study of the NTCWG for locally advanced prostate cancer demonstrated a significant decrease in local-regional failure (11 vs 32%) at 5 years, favoring the neutron arm. Furthermore, biochemical measures of disease control also favored the neutron arm with prostate specific antigen (PSA) levels elevated in 17% of the neutron-treated patients compared to 45% of the photon-treated patients at 5 years. At the 5-year analysis, no significant difference in survival was observed between the two arms; however, longer follow-up is necessary to assess the ultimate impact of improved local-regional control on survival. An analysis of complications in this series revealed the importance of beam shaping and treatment planning capabilities in maintaining long-term sequelae following neutron irradiation at an acceptably low level.

Actuarial Analysis↗
PubMed1996

Expanded pelvic radiotherapy fields for treatment of local-regionally advanced carcinoma of the cervix: outcome and complications.

OBJECTIVE: Recent anatomic and radiographic studies have indicated that standard external beam radiation portals may not adequately treat the volume at risk in patients with local-regionally advanced cervical cancer. A feasibility study was undertaken to evaluate toxicity, outcome, and patterns of failure in patients with advanced cervical cancer treated by expanded pelvic radiation fields. STUDY DESIGN: Thirty-eight women with stages IIB and III cancers of the cervix confined to the pelvis were irradiated with curative intent with expanded pelvic radiation portals. Anteriorly and posteriorly, the median field length and width were 20 and 17.5 cm, respectively. Lateral fields had a median width of 16.5 cm, and the posterior border encompassed the entire sacral silhouette. The median external beam whole-pelvis dose was 4140 cGy, with overall point A dose boosted by brachytherapy to 8315 cGy. RESULTS: Stage IIB patients (n = 22) had a 4-year actuarial local control rate of 70%, freedom from distant metastases rate of 62%, and disease-specific survival rate of 76%. In stage III disease (n = 16), the 4-year actuarial local control, freedom from distant metastases, and disease-specific survival rates were 80%, 48%, and 53%, respectively. Radiographically determined nodal status was an important predictor of disease-specific survival and distant metastases but not local control. The 4-year disease-specific survival rate was 40% in 11 patients with nodal disease compared with 71% in 27 node-negative patients (p < 0.01). The rate of freedom from distant metastases was 36% in node-positive patients versus 67% in node-negative cases (p < 0.01). The actuarial overall 4-year severe late complication rate was 14.8%. CONCLUSION: This study has demonstrated that expanded fields for pelvic radiotherapy is feasible, well tolerated, and therapeutic. The pelvic field design concepts presented should be integrated into radiation oncology practice.

Antineoplastic Agents↗
PubMed1995

Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography.

PURPOSE: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studied in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. METHODS AND MATERIALS: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio > or = 1.4 by 120 min after injection. Serial FHVs were compared for each patient. RESULTS: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 3-65% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. CONCLUSIONS: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.

Aged↗
PubMed1995

Late injury of cancer therapy on the female reproductive tract.

The purpose of this article is to review the late effects of cancer therapy on the female reproductive tract. The anatomic sites detailed are the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is discussed. Clinical syndromes are presented. Tolerance doses of irradiation for late effects are rarely presented in the literature and are reviewed where available. Management strategies for surgical, radiotherapeutic, and chemotherapeutic late effects are discussed. Endpoints for evaluation of therapeutic late effects have been formulated utilizing the symptoms, objective, management, and analytic (SOMA) format. Late effects on the female reproductive tract from cancer therapy should be recognized and managed appropriately. A grading system for these effects is presented. Endpoints for late effects and tolls for the evaluation need to be further developed.

Dose-Response Relationship, Drug↗
PubMed1995

Effect of pentoxifylline on radiation-induced lung and skin toxicity in rats.

PURPOSE: There is currently substantial clinical interest in pentoxifylline as an inhibitor of radiation-related normal tissue injury. To further assess this drug's potential toxicity-sparing effects, pentoxifylline was studied in rats using a radiation-induced lung injury model. METHODS AND MATERIALS: Adult male rats were exposed to either sham irradiation or a single fraction of 21 Gy delivered to the left hemithorax. Four study groups were defined: those that received neither radiation nor pentoxifylline, those that received pentoxifylline (500 mg/L in drinking water) but no irradiation, those that underwent irradiation without pentoxifylline, and those that received both pentoxifylline and radiation. Lung injury was measured by changes in relative left:right lung perfusion ratios derived from quantitative gamma camera imaging of 99mTechnetium-macroaggregated albumin uptake in the pulmonary circulation. Serial scans were done over a 40-week period following radiation. Skin toxicity was also assessed. After 40 weeks, the animals were killed, and lung tissue was assayed for angiotensin converting enzyme activity as a marker for endothelial cell damage. RESULTS: Both groups of radiated (with or without pentoxifylline) rats showed equivalent acute sharp decreases in left:right lung perfusion ratios compared to the nonirradiated groups, reaching a mean nadir value of 0.29 at week 4. Irradiated lung perfusion in subsequent weeks in the radiation-only group showed minimal recovery, with a plateau mean ratio of 0.37 (0.36-0.39). However, there was apparent later recovery of lung perfusion in the radiation with pentoxifylline group from weeks 14 through 40, to a mean ratio of 0.47 (0.43-0.52) (p < 0.01 compared to the radiation-only group). Angiotensin converting enzyme activity correlated closely with lung perfusion data. No effect of pentoxifylline on acute or late skin toxicity was detected. CONCLUSIONS: This study suggests that pentoxifylline does not have any measurable effect on acute lung injury following hemithoracic irradiation in rats, but does result in sparing of later lung toxicity.

Animals↗
PubMed1995

Carcinoma of the male breast: update 1994.

In many ways, male and female breast cancers are similar, but do have some notable differences. Although the underlying etiology of male breast cancer may be partially due to hormonal or environmental changes, this disease is rare compared to female breast cancer. Most often, it presents as a painless lump, with estrogen receptor-positive infiltrating ductal carcinoma being the most common pathologic type. The main component of local therapy is either a radical or a modified radical mastectomy, with adjuvant chemotherapy proving useful. Estrogen receptor-positive tumors respond well to hormonal therapy. More research is needed in order to: (1) further characterize the molecular biological properties of male breast cancer tumors, (2) further investigate the role of adjuvant chemotherapy, and define successful regimens, and (3) determine optimal chemotherapy regimens in the treatment of metastatic disease. As this disease is a relatively rare condition, whenever possible, all patients should be allowed to participate in national cooperative group studies.

Breast Neoplasms, Male↗
PubMed1995

The use of intraoperative radiation therapy in radical salvage for recurrent cervical cancer: outcome and toxicity.

OBJECTIVE: Our purpose was to evaluate the contribution of intraoperative radiation therapy in the management of recurrent cervical cancer. STUDY DESIGN: Twenty-two patients were treated with electron beam intraoperative radiation therapy for recurrent cervical cancers that were confined to the pelvis but were too extensive to be adequately treated by radical surgery alone. All patients underwent extensive surgical dissection for exposure and maximal tumor resection. Doses of intraoperative radiation therapy ranged from 14 to 27.8 Gy (median 22 Gy). Twelve patients received intraoperative radiation therapy to address gross residual disease, and 10 patients were treated for microscopically positive or close surgical margins. RESULTS: The five-year disease-specific survival and local control rates were 43% and 48%, respectively. There were trends toward better local control and disease-specific survival in patients with microscopic residual disease compared with those with gross residual disease. Seven patients had peripheral neuropathy related to treatment, and four of these cases resolved. CONCLUSION: In carefully selected cases intraoperative radiation therapy contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall.

Combined Modality Therapy↗
PubMed1994

Caffeine consumption is associated with decreased severe late toxicity after radiation to the pelvis.

PURPOSE: Recent studies have suggested that pentoxifylline, a methylxanthine, can prevent or ameliorate late radiation injury in animals and humans. Caffeine is a commonly consumed methylxanthine that provides a model for evaluating the impact of this category of drugs on radiation injury. A retrospective study was undertaken to determine if there is an association between caffeine consumption and a lower incidence of late radiation toxicity. METHODS AND MATERIALS: From 1984 through 1990, 82 patients with cervical cancer and 53 patients with endometrial cancer were treated with primary or adjuvant radiation therapy at the University of Washington. Patients were interviewed regarding ingestion of caffeine-containing beverages, and average daily caffeine consumption during the time of radiotherapy was estimated. The evaluable patients (42 cervical, 31 endometrial) were stratified by quantity of caffeine consumption for correlation with the incidence of radiation toxicity. RESULTS: Acute radiation toxicity was not associated with caffeine consumption for cervical or endometrial cancer. There was a nonstatistically significant trend toward a decrease in overall late radiation toxicity with increased caffeine intake for cervical cancer patients. Subgroup analysis revealed this trend to be attributable to a decreased incidence of severe late radiation injury in cervical cancer patients who consumed higher levels of caffeine at the time of their radiotherapy (p = 0.02). This relationship was not observable for late toxicity in the endometrial cancer patients due to the low incidence of severe late injury following radiation for that disease. CONCLUSIONS: This investigation is supportive of previous studies showing a radioprotective effect for pentoxifylline, and suggests that the mechanisms of radioprotection may be common to methylxanthines as a drug class.

Caffeine↗
PubMed1994

Effect of radiation fraction size on local control rates for early glottic carcinoma. A model analysis for in vivo tumor growth and radio-response parameters.

BACKGROUND: Two recent studies have suggested that the probability of local control for early glottic carcinoma (stages T1 and T2) following radiation therapy is lower when daily fractions of 1.8 Gy are given instead of 2.0 Gy when the total dose is kept constant at approximately 66 Gy. METHODS: We reviewed our experience with a total of 42 patients with T1, N0, M0 squamous cell carcinoma of the glottic larynx who were treated with radiation alone during the period 1979 to 1989. All patients received conventional fractionation radiation therapy (one treatment per day, 5 days per week). Eight patients received 2.0 Gy per fraction for an average total dose of 64.8 Gy, and 34 patients received 1.8 Gy per fraction for an average total dose of 66.7 Gy. We also calculated overall survival statistics. Combining the clinical data from our series and those of patients from other series (171 total patients), we analyzed the tumor response curve and doubling time for early glottic carcinoma by using a time-dependent, linear quadratic equation model. The analysis is valid for the typical range of radioresponsiveness for most tumors in healthy tissue. RESULTS: Using statistical z analysis, we noted a significant difference in the local control rates at 5 years, with better local control in the group that received 2.0 Gy per fraction (100% vs 70%). Our results for the calculated doubling time and tumor response curves correspond with experimental values for in vitro squamous cell carcinoma systems. CONCLUSION: It appears from the literature and from our data that the control rates for T1, N0, M0 glottic carcinoma may be significantly improved by using 2.0 Gy per fraction dose vs 1.8 Gy per fraction dose. Our analysis has provided a model of in vivo tumor response of early glottic carcinomas based on reported local control rates using these two different treatment regimens.

Carcinoma, Squamous Cell↗
PubMed1994

Fast neutron radiotherapy. The University of Washington experience.

An overview of the University of Washington neutron radiotherapy facility is presented. The utility of the multi-leaf, programmable, variable collimator is emphasized. Due to success in the treatment of salivary gland tumors, such patients comprise an ever increasing portion of the patients being treated. A cooperative randomized clinical trial for the treatment of salivary gland tumors was undertaken comparing fast neutrons against photon/electron radiation. At ten years, there was a statistically significant improvement in local/regional control for the neutron group (56% vs 25%, p = 0.009), but there was no improvement in survival (15% vs 25%, p = n.s.). Distant metastases were the primary reason for the failure of improved local/regional control to impact survival in the neutron group. The University of Washington experience is summarized with special emphasis on the treatment of adenoid cystic carcinomas. Excellent local/regional control can be achieved with neutrons even for large tumors arising in the paranasal sinuses. We conclude that the potential morbidity of a surgical debulking procedure is not warranted in most clinical situations.

Adult↗
PubMed1994

Fast neutron radiation therapy. Results of phase III randomized trials in head and neck, lung, and prostate cancers.

The results of phase III trials comparing neutrons to photons for head and neck squamous cell cancers, non-small cell lung cancers, and prostate adenocarcinomas are reviewed, with emphasis given to the most recent U.S. National Cancer Institute sponsored randomized clinical studies in which fast neutrons were delivered using modern, hospital-based, high-energy, isocentric-capable cyclotrons. In locally advanced squamous cell head and neck cancers, neutrons showed no convincing advantage over photons. Fast neutron radiotherapy may have provided a therapeutic benefit in selected patients with inoperable non-small cell lung cancers. For locally advanced prostate adenocarcinomas, neutron therapy resulted in significantly superior clinical and histological loco-regional tumor control, which may translate to improved survival with additional follow-up. In general, severe late complications were more frequent with neutrons, especially in patients treated on older physics laboratory-based equipment. Even with modern state-of-the-art neutron generators, careful beam collimation and treatment planning are required to minimize side effects.

Adenocarcinoma↗
PubMed1994

Positron emission tomography. A new tool for characterization of malignant disease and selection of therapy.

Present therapy for cancer patients is based primarily on tumor histology and anatomy. Despite treatment advances, clinicians have often been frustrated by their inability to assess tumor biology. Metabolic imaging by positron emission tomography is a promising new technology that has opened up a whole realm of study in oncology. Glucose metabolism, hemodynamics, oxygen utilization, protein synthesis and thymidine incorporation may yield valuable data regarding tumor aggressiveness and stage, and allow assessment of tumor response early during treatment, before morphological changes are detectable. Other metabolic determinations, including tumor hypoxia and estrogen receptor density, may predict tumor response to therapy, and lead to selection of more appropriate treatment regimens, such as with neutrons or hypoxic cell sensitizers for documentably hypoxic tumors. While further clinical validation is required, positron emission tomography promises to provide vital information complementary to present anatomical imaging modalities that will aid oncologists in optimal management of their patients.

Cell Division↗
PubMed1994

Common emergencies in cancer medicine: infectious and treatment-related syndromes, Part II.

This article completes a summary of the common medical emergencies that can occur as a result of infectious processes (Part I) and antitumor treatment secondary to chemotherapy, biological response modifiers, or radiotherapy (Part II). The use of high-dose cytotoxic agents, coupled with the common instillation of indwelling central venous access devices, have altered the spectrum of infectious etiologies that are appreciated in clinical practice. In addition, a myriad of cytotoxic agents and radiotherapeutic treatment schemes are used widely in clinical oncologic practice. While most of their related side effects are not considered life-threatening emergencies, they can be fatal if not recognized early and treated promptly. Moreover, some of these infectious and treatment-related sequelae can be prevented. This article highlights some of these clinical observations.

Antineoplastic Agents↗
PubMed1993

Femoral vessel depth and the implications for groin node radiation.

PURPOSE: To quantify, based on pretreatment computer tomographic measurements, potential groin node depths, which will aid in optimal treatment planning for patients requiring groin node radiation. METHODS AND MATERIALS: The pretreatment computer tomographic scans of 50 gynecologic cancer patients were reviewed to determine the distance of each femoral vessel beneath the overlying skin surface, as an indicator of potential groin node depth. Correlative data regarding height and weight were obtained from patient medical records, and were used to calculate the Quetelet index, defined as (weight in kg)/(height in m)2. Treatment parameters of 5 patients who failed prophylactic groin radiation in a recently published study were assessed to determine if underdosage represented a possible cause of failure. RESULTS: Individual femoral vessel depths ranged from 2.0 to 18.5 cm. When the depths of all four femoral vessels were averaged in each patient, the mean "4-vessel average" depth for this patient population was 6.1 cm. The median Quetelet index for the group was 25.6, and there was a strong correlation between femoral vessel depth and patient Quetelet index. Recalculation of doses provided to the 5 patients failing prophylactic groin radiation in the Gynecologic Oncology Group study showed that all had received potential tumor doses < 4700 cGy, with 3 patients being underdosed by > 30%. CONCLUSION: While surgery is often indicated in the management of patients with potential groin node metastases, the role of prophylactic groin radiation should not be rejected. Data from this study may aid in the optimal design and implementation of groin node radiotherapy.

Adult↗
PubMed1993

Neutron vs. photon radiation therapy for inoperable regional non-small cell lung cancer: results of a multicenter randomized trial.

PURPOSE: To determine, with a prospective, multicenter randomized study, whether fast neutron radiation therapy improves the outcome for patients with non-small cell lung cancer, as compared to conventional photon radiotherapy. METHODS AND MATERIALS: From September 1986 to March 1991, a total of 200 patients with inoperable regional non-small cell lung cancer were randomized to 20.4 Gy in 12 fractions with neutrons versus 66 Gy in 33 fractions with photons. Inoperable patients with Radiation Therapy Oncology Group Stages I, II, III, or IV(M0) disease, Karnofsky Performance Score > or = 70, and who had received no previous therapy for their non-small cell lung cancer were eligible for the study. Of the 200 patients randomized, a total of 193 patients, 99 on the neutron arm and 94 on the photon arm, were eligible for analysis. The two treatment groups were balanced with regards to prognostic factors. At the time of this analysis, the median at-risk follow-up was 33 months, with a minimum follow-up of 16 months. RESULTS: No difference in overall survival was observed; however, there was a statistically significant improvement in survival for patients with squamous cell histology (p = 0.02), and a trend toward improved survival for those with favorable prognostic factors (i.e., patients who were not T4, N3, and had no pleural effusion or weight loss > 5% from baseline) (p = 0.15), favoring the neutron-treated group. With the exception of skin and subcutaneous changes, acute and late toxicity was similar in both arms. CONCLUSION: In selected patients with inoperable regional non-small cell lung cancer (e.g., squamous cell histology, favorable prognostic factors), fast neutron irradiation provides a therapeutic benefit over conventional photon radiotherapy.

Adult↗