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K J Russell

Publications and source records attributed to K J Russell.

At least 37 records · Page 2Linked to original sources
PubMed1995

Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells.

We have examined the effect of abrogation of the G2 checkpoint on the radiosensitivity of G1 checkpoint-proficient and G1 checkpoint-deficient cells. A549 human lung adenocarcinoma cells were transduced with the E6 oncogene of the human papillomavirus type 16 to eliminate their radiation-induced G1 arrest. These E6+ cells exhibited a dose-dependent increase in radiation resistance compared to control A549 cells transduced with the vector alone. Treatment (96 h) with 2 mM caffeine resulted in an abrogation of the cellular G2 checkpoint in both E6+ and control cells and a differential radiosensitizing effect on the two cell lines such that the E6+ clones and the vector controls became equally radiosensitive. These data show that human tumors which are radioresistant due to the loss of the p53-mediated G1 checkpoint can be made radiosensitive by abrogation of the G2 checkpoint. The implications of these results for cancer therapy are discussed.

Adenocarcinoma↗
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↗
PubMed1994

Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial.

PURPOSE: To evaluate the effectiveness of fast neutron radiation therapy in treatment of locally advanced carcinomas of the prostate. METHODS AND MATERIALS: From April 1986 to October 1990, 178 patients were entered on a prospective, multi-institutional randomized study of the NCI-sponsored Neutron Therapy Collaborative Working Group. This trial compared external beam photon irradiation (7000-7020 cGy) with external beam neutron irradiation (2040 ncGy) for patients with high-grade T2 or T3-4, N0-1, M0 adenocarcinomas of the prostate. Eighty-nine patients were randomized to each treatment. Six patients were subsequently judged to be ineligible, leaving 85 photon and 87 neutron randomized patients eligible for analysis. RESULTS: With a follow-up time ranging from 40 to 86 months (68 months median follow-up) the 5-year actuarial clinical local-regional failure rate for patients treated with neutrons was 11%, vs. 32% for photons (p < 0.01). Incorporating the results of routine posttreatment prostate biopsies, the resulting "histological" local-regional tumor failure rates were 13% for neutrons vs. 32% for photons (p = 0.01). To date, actuarial survival and cause-specific survival rates are statistically indistinguishable for the two patient cohorts, with 32% of the neutron-treated patient deaths and 41% of the photon-treated patient deaths caused by prostate cancer (p = n.s.). Prostate specific antigen (PSA) values were elevated in 17% of neutron-treated patients and 45% of photon-treated patients at 5 years (p < 0.001). Severe late complications of treatment were higher for the neutron-treated patients (11% vs. 3%), and were inversely correlated with the degree of neutron beam shaping available at the participating institutions. Neutron treatment delivery utilizing a fully rotational gantry and multileaf collimator did not result in an increase in severe late effects when compared to photon treatment. CONCLUSION: High energy fast neutron radiotherapy is safe and effective when adequate beam delivery systems and collimation are available, and it is significantly superior to external beam photon radiotherapy in the local-regional treatment of large prostate tumors.

Adenocarcinoma↗
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↗
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

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↗
PubMed1993

Fast neutron radiotherapy for locally advanced prostate cancer. Final report of Radiation Therapy Oncology Group randomized clinical trial.

Between June 1977 and April 1983 the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized trial investigating the use of fast neutron radiotherapy for patients with locally advanced (Stages C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation or fast neutron radiation used in a mixed-beam (neutron/photon) treatment schedule. A total of 91 analyzable patients were entered into the study, and the two patient groups were balanced with respect to the major prognostic variables. Actuarial curves are presented for local/regional control and "overall" survival. Ten-year results for clinically assessed local control are 70% for the mixed-beam group versus 58% for the photon group (p = 0.03) and for survival are 46% for the mixed-beam group versus 29% for the photon group (p = 0.04). This study suggests that a regional method of treatment can influence both local tumor control and survival in patients with locally advanced adenocarcinoma of the prostate gland.

Adenocarcinoma↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Accelerated fractionation radiation therapy for liver metastases: selection of an optimal patient population for the evaluation of late hepatic injury in RTOG studies.

The palliation of hepatic metastases represents a major therapeutic problem in oncology. The generally unfavorable prognosis of patients with liver metastasis may complicate the evaluation of the efficacy and toxicity of various therapeutic modalities. The Radiation Therapy Oncology Group (RTOG) is evaluating new accelerated fractionation schemes for hepatic irradiation. In designing this study it became necessary to identify a favorable subpopulation of patients with an expected median survival of 6 months in whom the late effects of treatment could be evaluated. Data from two RTOG liver metastases studies (7605 and 8003) were analyzed using multi-variate techniques. Cases with a serum bilirubin level of greater than 1.5 mg%, performance score of less than 50, and gastric or pancreatic primary carcinomas were initially excluded because of the adverse influence of these factors on survival. One hundred and ninety cases met the criteria for inclusion in this analysis. A loglinear model was used to identify the patient characteristics associated with a favorable prognosis for survival. These included a performance score of 80-100, colorectal carcinoma primary, and no extrahepatic metastases. A logistic regression equation was derived and confirmed that the probability of surviving at least 6 months depended on the effects of performance score, primary site and the presence or absence of extra-hepatic metastases. Patients with all three favorable factors constituted 30% of the evaluable study population and had a predicted survival of 50% at 6 months. A patient population with these characteristics will be used to study the late effects of accelerated fractionated radiation therapy on the liver.

Breast Neoplasms↗
PubMed1990

Combined 5-fluorouracil and irradiation for transitional cell carcinoma of the urinary bladder.

Thirty-four patients have completed treatment on a bladder-preservation protocol using primary irradiation combined with infusion 5-fluorouracil (5-FU). 4,000 cGy pelvic irradiation was delivered in 5 weeks, with 1,000 mg/m2/day of 5-FU administered as a 96 hr infusion on days 1-4 of week 1 and 4. After a 3-week rest period, patients eligible for cystectomy underwent cystoscopy and biopsy. Those with residual tumor underwent cystectomy, and those without tumor received an additional cycle of chemotherapy and irradiation. Patients ineligible for cystectomy for reasons medical, surgical, or refusal received a third cycle without the 4-week delay or re-evaluation. With a median follow-up of 18 months (range 2-45 months), and with 25/34 patients having T3 (16) or T4 (9) tumors, 17 patients are NED, 4 have died of intercurrent deaths, 7 have died with bladder cancer, and 6 are alive with tumor (2 confined to the bladder). The actuarial cancer-specific survival for the entire group of patients is 64% (+/- 12%) at 45 months, with a freedom from relapse of invasive cancer of 54% (+/- 10%). Twenty-four of the 34 patients retained intact bladders, with 20/24 reporting entirely normal voiding. Of 18 potential surgical candidates, 13/16 (81%) who underwent pathologic re-staging after 2 cycles of chemoradiotherapy had no histologic evidence of residual cancer. Of these 13 patients, 8 remain NED and 2/13 have locally recurrent non-invasive tumors only. Treatment was well-tolerated, with 28/34 patients having received 100% of the planned 5-FU and 34/34 having received greater than 80%. This regimen appears more successful than radiotherapy alone in achieving complete tumor responses, and is an attractive alternative for patients who are unable to receive more aggressive chemotherapy/radiation combinations.

Adult↗
PubMed1989

Fast neutron radiotherapy for locally advanced prostate cancer. Update of a past trial and future research directions.

Between June, 1977, and April, 1983, the Radiation Therapy Oncology Group (RTOG) sponsored a phase III study comparing fast neutron radiotherapy as part of a mixed beam (neutron/photon) regimen with conventional photon (x-ray) radiotherapy for patients with locally advanced (Stages C and D1) adenocarcinoma of the prostate. A total of 91 analyzable patients were entered into the study with the two treatment groups balanced in regard to all major prognostic variables. The current analysis is for a median follow-up of 6.7 years (range 3.4-9.0 yrs.). The results are statistically significant in favor of the mixed-beam group of all parameters mentioned. At five years the freedom from local/regional relapse rate is 81 percent on the mixed-beam arm compared with 60 percent on the photon arm. The actuarial overall survival rate at five years is 70 percent on the mixed beam compared with 56 percent on the conventional photon arm. The determinantal survival at five years (which excluded death due to intercurrent disease in patients clinically free of cancer) was 82 percent on the mixed-beam arm compared with 61 percent on the photon arm. The type of therapy appeared to be the most important predictor of both local tumor control and patient survival in a step-wise Cox analysis. There was no difference in the treatment-related morbidity for the two patient groups. Mixed-beam therapy may be superior to standard photon radiotherapy for treatment of locally advanced prostate cancer.

Adenocarcinoma↗
PubMed1989

Response of mediastinal Hodgkin's disease to radiotherapy: rate of tumor regression not predictive of outcome.

The record of 18 patients with Stage II Hodgkin's disease and large mediastinal masses, who received radiation therapy as sole treatment for their disease, were reviewed. The ratio of each patient's maximum tumor diameter to his maximum transthoracic diameter was measured from radiographs taken prior to treatment, and at two intervals approximating 1/3 and 2/3 the total radiation dose. The slopes of the resulting graphed data points were correlated with patient outcomes. No correlation could be drawn between prompt or slow tumor regression and freedom from tumor recurrence. It is concluded that the rate of tumor mass regression in Hodgkin's disease is not predictive of the ultimate success or failure of radiation therapy, and should not be used as a criterion by which to judge the need for additional systemic chemotherapy.

Female↗
PubMed1989

Improved radiotherapy treatment planning for spinal cord tumors using gadolinium enhanced MR imaging.

Primary intramedullary spinal cord tumors are frequently difficult to localize for radiation treatment planning. Conventional imaging techniques, including unenhanced magnetic resonance (MR) scans, cannot clearly distinguish residual tumor from surrounding normal spinal cord. Recently, contrast agents have been developed for MR that have considerable promise for improving tumor volume definition. This report describes the impact of contrast-enhanced MR on the treatment planning process for four patients with primary spinal cord tumors and discusses the significance of this technique for patients with these neoplasms.

Adult↗
PubMed1989

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↗
PubMed1989

Neutron radiation therapy for unresectable non-small-cell carcinoma of the lung. A review.

Over 200 patients have been entered in five studies investigating the use of fast neutron radiation therapy in the treatment of non-small-cell carcinomas of the lung since 1983. The results of these studies have been inconsistent. Most studies did not show survival rates or local control advantages over standard photon radiation therapy. Side effects from studies employing mixed photon-neutron treatment plans or clinically oriented, high-energy cyclotrons were seen to be comparable to those of standard courses of radiation therapy, representing a considerable improvement over those studies utilizing low-energy cyclotrons for a full course of radiation therapy, which resulted in unacceptably high complication rates. A new phase III study utilizing high-energy isocentric neutron beams has been designed and implemented, and over 100 patients have been entered to date. The current status of fast neutron radiation therapy in the treatment of non-small-cell lung cancer is reviewed.

Carcinoma, Non-Small-Cell Lung↗