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W J Koh

Publications and source records attributed to W J Koh.

52 records · Page 3Linked to original sources

Combined radiotherapy and chemotherapy in the management of local-regionally advanced vulvar cancer.

PURPOSE: To determine, in a retrospective single institutional study, the role of concurrent radiotherapy and chemotherapy in the treatment of local-regionally advanced vulvar cancer. METHODS AND MATERIALS: From 1984 to 1991, 20 patients with locally extensive primary or recurrent carcinoma of the vulva were treated with initial combined radiotherapy and chemotherapy. Seven patients had Federation Internationale de Gynecologie et d'Obstretrique Stage III disease, 10 had Stage IV disease, and three were treated for recurrent disease. None of these patients were considered candidates for primary radical vulvectomy and groin node dissection. Median radiation doses to regions of microscopic disease and gross tumor were 40 Gy (range 30-54 Gy) and 54 Gy (34-70.4 Gy), respectively. All patients received 2 or 3 cycles of 5-Fluorouracil concurrently with radiotherapy. In addition, five patients received Cis-platinum, and one Mitomycin-C. Median at-risk follow-up interval was 37 months. RESULTS: Ten patients had complete resolution of tumor to initial chemoradiotherapy, and eight of these have remained free of tumor relapse. Eight other patients had partial responses, with tumor bulk reduced by > 50%, while the remaining two patients had local-regionally progressive disease. Six of the patients with partial responses had residual tumor successfully resected, although four subsequently recurred. For the entire group of 20 patients, the actuarial 3- and 5-year local control rates were 48% each, and the corresponding disease-specific survival rates were 59% and 49%. There was a suggestion that better local control was obtained in patients who received gross tumor radiation doses > or = 50 Gy. Skin reaction was the major acute toxicity and responded well to conservative management. Long-term sequalae were limited to skin and subcutaneous atrophy. CONCLUSION: These results indicate that initial combined radiotherapy and chemotherapy is effective in the management of advanced vulvar cancer.

Adenocarcinoma↗

Radiation recall skin toxicity with bleomycin in a patient with Kaposi sarcoma related to acquired immune deficiency syndrome.

BACKGROUND: Radiation recall is a recurrence of acute toxicity within a previously quiescent radiation field that occurs with subsequent administration of chemotherapy. METHODS: A patient with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma (KS) who had radiation recall is reported. The patient was participating in a randomized prospective trial of radiation treatment regimens for KS. Each lesion was randomized to one of three possible radiation fractionation schemes. All lesions were photographed and measured before treatment with radiation. RESULTS: Two skin sites developed erythema and dry desquamation 18 days after completion of radiation therapy to a dose of 40 Gy in 20 fractions. These reactions took place after the second dose of bleomycin administered intravenously on a weekly basis. The reactions were exacerbated by oral etoposide therapy, which was started 4 days after the recall phenomenon was noted. Other cutaneous sites treated with 8 Gy in a single fraction and 20 Gy in ten fractions during the same time period showed no sign of recall skin toxicity. CONCLUSIONS: The authors believe this to be the first report of radiation recall toxicity after bleomycin therapy and of a radiation dose response related to this phenomenon. The potential for radiation recall toxicity should be considered in treatment decisions pertaining to patients with AIDS-associated KS.

AIDS-Related Opportunistic Infections↗

The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms.

Fifty-three patients with locally advanced salivary gland malignant neoplasm were treated with fast neutron radiation therapy. All patients received treatment for gross inoperable, residual unresectable, or recurrent disease--clinical situations in which results using photon irradiation were suboptimal. With a median follow-up of 42 months and a minimum follow-up of 1 year, locoregional tumor control in the treatment field was achieved in 92% (48 of 52) of patients. An additional eight patients had regional failures outside the treatment field, resulting in an overall locoregional tumor control rate of 77% (40 of 52). The 5-year actuarial locoregional control rates were 65% overall and 75% in patients with node-positive disease. Grouping patients according to prior treatment status, actuarial 5-year locoregional control rates were 92% for patients treated definitively (without a prior surgical procedure), 63% for those treated postoperatively for gross residual disease, and 51% for those treated for recurrent disease after a surgical procedure. The P values associated with these differences were 0.12 and 0.01, respectively. There were no instances of radiation-induced facial nerve damage. This study suggests that neutron irradiation alone should be the therapy of choice in the treatment of advanced-stage salivary gland tumors and that surgery should be limited to those patients in whom disease-free margins can be obtained. The potential morbidity of a debulking surgical procedure before neutron irradiation is not warranted by an improvement in loco-regional control over that achievable with neutron therapy alone.

Adult↗

Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole.

Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18]FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of greater than or equal to 1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.

Cell Hypoxia↗

Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy.

The records of 143 patients treated at 5 institutions with external beam megavoltage irradiation for localized prostatic cancer were reviewed to evaluate post-treatment changes in prostate specific antigen (PSA) in the context of subsequent events. Complete responders were defined as patients clinically well with normal PSA, clinical failures were patients with documented local tumor recurrence or distant metastases and chemical failures were patients clinically well but with a PSA level above the upper limits of normal. Correlations with pre-treatment PSA values were also made for the 50 of 143 patients for whom pre-treatment PSA data were available. Median patient followup was 27 months (range 18 to 91 months). The data were analyzed with parametric and nonparametric univariate and multivariate statistical procedures. Pre-treatment PSA levels increased with increasing tumor stage (p = 0.004) but not with increasing summed Gleason pattern scores (p = 0.15). The probability of remaining a complete responder decreased with increasing stage (p = 0.008) but not with increasing Gleason score (p = 0.14). Increasing pre-treatment PSA correlated with clinical failure (p = 0.01) and chemical failure (p = 0.006). Of the patients with a pre-treatment PSA level of less than 4 times the upper limits of normal 83% remained as complete responders compared to 30% of those with a higher pre-treatment PSA (p = 0.0002). The return of PSA levels to the normal range within 6 months after treatment was strongly correlated with a favorable outcome when analyzed by multivariate logistic regression. The status at last followup of patients who had a normal PSA level at 6 months versus those with an elevated PSA level 6 months after treatment is 94% versus 8% for complete responders (p = 0.0001), 0% versus 60% for clinical failures (p = 0.002) and 6% versus 32% for chemical failures (p = 0.14). Similar results occurred when analyzing outcomes in relationship to PSA normalization within 12 months after treatment (p = 0.001 for clinical failures, p = 0.02 for chemical failures and p = 0.001 for complete responders). We conclude that the pre-treatment level of PSA is an independent prognostic factor for prostate cancer patients treated with primary radiation therapy, and that the failure of PSA to return to the normal range within 1 year after completion of treatment identifies a group of patients at high risk for tumor recurrence.

Adenocarcinoma↗

Gynecologic radiotherapy fields defined by intraoperative measurements.

Whole-pelvis radiation therapy has been traditionally delivered through fields, the dimensions of which have been determined by convention and based largely on textbook anatomic landmarks. Since July 1986, 100 patients have had intraoperative retroperitoneal measurements carried out at the time of radical surgery in an effort to examine this anatomic basis for field dimensions. Structural measurements of the pelvic and paraaortic arterial branches were made in reference to the lumbosacral prominence to correlate with lymphatic pathways. The mean level of the aortic bifurcation was found to be 6.7 cm above the lumbosacral prominence. The mean level of the bifurcation of the common iliac artery was 1.7 cm above this reference point on the right and 1.4 cm above on the left. Both common iliac bifurcations were cephalad to the level of the lumbosacral prominence in 87% of patients. In only three patients were both bifurcations located below this level. Transverse pelvic dimension measurements demonstrated a width of 12.3 cm at the level of the obturator fossa and of 13.0 cm at the most inferior outside width of the external iliac arteries. To establish a simple external reference which could assist in defining radiotherapy field widths, the maximal separation of the femoral arteries at the level of inguinal ligaments was measured and averaged 14.6 cm. These data suggest that conventional fields frequently fail to correspond to true anatomic landmarks and that to optimally cover the lymphatics in radiotherapy, fields should, ideally, be based on intraoperative measurements. If such surgical guides are not available, we would suggest that standard whole-pelvis radiotherapy for cervical cancers should employ anterior and posterior fields with widths of at least 16 cm which will fully include the bifemoral separation. A superior border at the L4-L5 interspace is required to cover lymphatic pathways to the mid-common iliac nodal level. It may also be convincingly pointed out that the attachments of the uterosacral and cardinal ligaments are clearly posterior to the rectosigmoid, mandating lateral fields that should encompass the entire anterior sacral silhouette.

Female↗

Transient and chronic neurological complications of fast neutron radiation for adenocarcinoma of the prostate.

The records of 132 patients participating in clinical trials using fast neutron (n = 94), mixed neutron and photon (n = 16), or conventional photon (n = 22) irradiation for primary management of prostatic cancer were retrospectively reviewed to assess treatment-related neurological complications. With a median follow-up of 14 months (range 1 to 101 months), 31/132 patients (26 neutron, 3 mixed beam, 2 photon) have experienced either sciatica beginning during or shortly after treatment, or diminished bladder or bowel continence that developed at a median time of 6.5 months following treatment. Sciatica responded to oral steroids and was usually self-limited, whereas sphincter dysfunction appears to be permanent. Pre-treatment risk factors for complications included a history of hypertension, diabetes, cigarette smoking or peripheral vascular disease, with 81% of affected patients having one or more risk factors compared with 55% of unaffected patients (p = 0.01). Seven patients have moderate (5) or severe (2) residual problems, all in the cohorts receiving neutrons (6/7) or mixed beam therapy (1/7).

Adenocarcinoma↗

Current use of electron beam therapy in the United States.

Owing to their physical characteristics, electron beams are a crucial component in radiotherapy of human tumors. Besides their main indications (skin cancers, head and neck tumors, breast, chest wall recurrence, low pelvic tumors) other types and sites of malignancies are to be considered: skin lymphomas, soft tissue sarcomas, Kaposi's sarcoma in AIDS patients, as well as Intra Operative Radiotherapy.

Electrons↗

Radiolabelled fluoromisonidazole as an imaging agent for tumor hypoxia.

Fluoromisonidazole labeled with H-3 or F-18 has been tested as a quantitative probe for hypoxic cells in vitro and in rodent and spontaneous dog tumors in vivo. In V-79, EMT-6(UW), RIF-1, and canine osteosarcoma cells in vitro, the binding of 50 microM [H-3]Fluoromisonidazole was 50% inhibited by 1000-2000 ppm O2, relative to binding under anoxic conditions. After a 3 hr incubation with labeled drug, the anoxic/oxic binding ratios ranged from 12 to 27 for the four cell types. Retention of [H-3]fluoromisonidazole 4 hr after injection was greater in large KHT tumors (400-600 mm3) with an estimated hypoxic fraction greater than 30%, than in smaller tumors (50-200 mm3) with an estimated hypoxic fraction of 7-12%. RIF-1 tumors, with an estimated hypoxic fraction of 1.5%, retained the least label, with tumor: blood ratios ranging from 1.7 to 1.9. Spontaneous dog osteosarcomas were imaged with a time of flight positron emission tomograph for up to 5 hr following injection of [F-18] fluoromisonidazole. Analysis of regions of interest in images allowed creation of dynamic tissue time activity curves and calculation of tissue uptake in cpm/gram. These values were compared to radioactivity in plasma. In all cases, retention in some tumor regions exceeded that in plasma and in normal tissue, such as muscle or brain, by 3 to 5 hr post injection. Uptake of fluoromisonidazole in tumors was heterogeneous, with ratios of maximum to minimum uptake as high as 4 in different regions of interest in the same tumor. Tumor:plasma values ranged from 0.28 to 2.02. The oxygen dependency of fluoromisonidazole retention was similar in a variety of cell types and was 50% inhibited by O2 levels in the transition between full radiobiological hypoxia and partial sensitization. The quantitative regional imaging of [F-18] fluoromisonidazole in spontaneous canine tumors at varying times post-injection lays the basis for imaging and modeling of oxygen-dependent drug retention in different regions of human neoplasms.

Adenocarcinoma↗

Combined intracavitary and external beam irradiation for superficial transitional cell carcinoma of the bladder: an alternative to cystectomy for patients with recurrence after intravesical chemotherapy.

A total of 17 patients with superficial transitional cell carcinoma of the bladder underwent treatment with pelvic external beam irradiation followed by an intracavitary 137cesium implant via a triple lumen Foley catheter. Of these patients 11 had recurrent and multifocal superficial cancer, with 8 having relapse after prior intravesical chemotherapy. External beam doses of 3,600 to 5,066 cGy. were followed by implant doses delivering 2,000 to 3,200 cGy. to the bladder mucosa, with the sum of external and intracavitary doses totaling 6,500 to 7,500 cGy. Of 15 patients evaluable with a median followup of 48 months, and including 13 followed for more than 2 years, 11 (73 per cent) remain free of disease, 3 (20 per cent) have recurrence in the bladder but have retained the bladder and only 1 has required cystectomy. All 4 failures occurred in the subgroup of 8 patients who had received prior intravesical chemotherapy. This bladder-sparing approach is well tolerated, is an alternative to cystectomy in patients with recurrent superficial transitional cell carcinoma of the bladder and in our series has salvaged 50 per cent (4 of 8) of the patients even after failure of intravesical chemotherapy.

Aged↗

Fast neutron teletherapy in advanced epidermoid head and neck cancer. A review.

An extensive review of clinical studies employing fast neutron teletherapy for advanced epidermoid carcinomas of the head and neck is presented. Head and neck tumors have represented an excellent study site because of their accessibility to physical examination for measurement of tumor response, and because early neutron beams have had poor depth dose characteristics, making the treatment of more deeply seated tumors technically difficult. A summary of the major trials comparing neutron and mixed-beam (combination neutron and photon) therapy with conventional therapy indicates no conclusive evidence of improvement in local control or survival rates for the experimental arms. Exceptions to this are the Hammersmith experience and the slightly higher lymph node control rates seen in two studies. An evaluation of toxicity indicates that with the new generation of cyclotrons, complication rates may approach parity with those of photon linear accelerators.

Carcinoma, Squamous Cell↗

Fast neutron radiation for inoperable and recurrent salivary gland cancers.

The current standard treatment of salivary gland cancers consists of surgical resection, with or without postoperative low linear energy transfer (LET) radiation, resulting in high locoregional control rates. However, tumor control prognosis is poor when conventional radiation is used alone for advanced, inoperable cases. An extensive review of the world's literature on fast neutron irradiation for inoperable, unresectable, or recurrent malignant salivary gland neoplasms is presented and compared with the experience using conventional low LET radiotherapy. The pooled data indicate a locoregional control rate of 67% for fast neutrons versus 25% for photons and/or electrons in the treatment of such advanced disease. The radiobiological rationale supporting this observed increase in tumor control is discussed. The overall significant late complication rate is 19%, but several suboptimal treatment factors were present that contributed substantially to the reported toxicity. With the modern machines and treatment techniques now available, the evidence overwhelmingly supports the role of fast neutron radiation as the treatment of choice for inoperable and recurrent salivary gland cancers.

Energy Transfer↗

Transitional cell carcinoma of the urinary bladder: histologic clearance with combined 5-FU chemotherapy and radiation therapy. Preliminary results of a bladder-preservation study.

Fourteen patients with transitional cell carcinoma of the urinary bladder were treated with 4,000 cGy of pelvic irradiation concurrent with two 96-hour infusions of 5-fluorouracil (5-FU). Three weeks after completion of this regimen, patients underwent repeat cystoscopy and deep-muscle biopsy at the site of their original neoplasms. Eight of 14 (57%) had no tumor left in the biopsy specimen, and they received an additional course of chemotherapy and radiation therapy to a total dose of 4,400 cGy to the pelvis and 6,000 cGy to the bladder. Five of the 14 had residual tumor in the biopsy specimen (one did not undergo biopsy) and went on to planned cystectomy. Two of the five had no tumor in the cystectomy specimen. Overall, ten of the 14 patients (71%) have been downstaged to a condition of P0 (no tumor) following 4,000 cGy and two courses of 5-FU. Of eight patients with retained bladders, seven remain well at a median follow-up of 7 months. At a range of follow-up of 3-21 months and a median of 7 months, 13 of 14 patients remain tumor-free. This regimen results in a greater percentage of downstaging than conventional irradiation alone, and may allow bladder preservation for those with radiation therapy- and chemotherapy-responsive tumors.

Adult↗

Radical reirradiation for recurrent or second primary carcinoma of the female reproductive tract.

Twenty-five women have been treated with a second course of irradiation for recurrent cancer or a second primary carcinoma arising within a previously irradiated pelvic volume. Fourteen patients have been rendered cancer-free (56%) with follow-up ranging from 10 to 61 months. Three of these patients have died of intercurrent disease. Seven of these patients have experienced major complications (50%), necessitating surgical intervention in three cases. The rationale for reirradiation and techniques of retreatment are discussed. Prognostic factors are analyzed and criteria for patient selection are identified.

Adult↗

Spectral analysis of Doppler ultrasonic flow signals by a personal computer.

This paper describes a method of performing spectral analysis on Doppler acoustical signals from peripheral blood vessels with the use of an Apple II plus personal computer. Digitization is accomplished with a commercially available analog-to-digital converter. The data are transformed with a fast Fourier technique, and the resultant information is plotted by an inexpensive X-Y plotter and/or on a television receiver.

Blood Vessels↗