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Biomedical subjects

K J Russell

Publications and source records attributed to K J Russell.

52 records · Page 3Linked to original sources

Fast neutron radiotherapy for the treatment of carcinoma of the urinary bladder. A review of clinical trials.

The major clinical investigation employing fast neutrons in the treatment of invasive bladder cancer are reviewed. Although data suggest that preoperative radiation schedules employing neutrons may result in a greater degree of pathologic downstaging than conventional precystectomy photon regimens, this has not led to an improved survival rate for neutron-treated patients over photon-treated patients. Randomized clinical trials comparing primary neutron irradiation and primary photon irradiation do not disclose an advantage for neutrons over photons as measured by survival rate or freedom from local tumor recurrence. The late complications in normal pelvic tissues following neutron irradiation with low-energy beams exceed those experienced after photon irradiation and have led to an unexpectedly high rate of treatment-related morbidity and mortality. A partial explanation for the toxicity may be attributed to the use of neutron beams with poor depth dose characteristics for the treatment of what is a deep-seated malignancy. An additional explanation is the documented lack of a differential in radioresponsiveness to neutrons between the bladder primary tumor and adjacent normal pelvic tissues.

Carcinoma, Transitional Cell↗

Fast neutron radiotherapy in the treatment of locally advanced adenocarcinoma of the prostate. Clinical experience and future directions.

The major clinical experiences using fast neutrons for the treatment of locally advanced prostatic carcinomas are reviewed. In all trials to date, there is evidence that treatment regimens employing a component of fast neutrons achieve results that equal or surpass those obtainable with conventional megavoltage external beam irradiation for comparable groups of patients. Late complications of neutron treatment have not exceeded the complication rate expected by photon irradiation. The structure of the current Radiation Therapy Oncology Group phase III randomized trial comparing neutron and photon treatment of patients with stages B2, C, and D1 disease is discussed.

Adenocarcinoma↗

Fast neutron radiotherapy for sarcomas of soft tissue, bone, and cartilage.

The basic radiobiological rationale for the use of fast neutron radiotherapy in the treatment of classically radioresistant tumors such as soft tissue sarcomas, osteogenic sarcomas, and chondrosarcomas is reviewed. There are no definitive randomized studies comparing high and low linear energy transfer radiotherapy for these tumor systems, but a review of published series is highly suggestive of a therapeutic advantage for fast neutrons. For soft tissue sarcomas, the local control rate is 53% (158 of 297) with fast neutrons, compared with 38% (49 of 128) with photons/electrons; for osteogenic sarcomas, the local control rate is 55% (40 of 73) with fast neutrons, compared with 21% (15 of 73) with photons/electrons; and for chondrosarcomas, the local control rate is 49% (25 of 51) with fast neutrons, compared with 33% (10 of 30) with photons/electrons. An ongoing clinical trial for these tumors is also described.

Bone Neoplasms↗

Prophylactic cranial irradiation for limited non-small cell lung cancer.

Seventy-three patients with biopsy-proven limited non-small cell lung cancer (NSCLC) were entered on a combined modality study at the University of Washington. Seventy-five percent (55 of 73) of the patients had a histologic diagnosis of adenocarcinoma or large cell carcinoma, whereas 25% (18 of 73) had squamous cell carcinoma. After two cycles of chemotherapy, patients without evidence of progressive disease received prophylactic cranial irradiation (PCI) and chest radiotherapy, followed by two additional cycles of chemotherapy. Brain computed tomography (CT) scans were performed at 3-month intervals after completion of therapy in all patients, and were additionally performed whenever signs or symptoms developed suggesting neurologic dysfunction or recurrent brain disease. Sixty-five patients were treated with PCI. No clinical or CT evidence of recurrence in the brain has developed in patients who completed PCI. PCI appears to be effective in greatly reducing the incidence of brain relapse in patients with limited NSCLC.

Brain↗

Fast neutron radiotherapy for advanced malignant salivary gland tumors.

Thirty-two patients with inoperable, recurrent, or gross residual malignant salivary gland tumors received fast neutron radiotherapy at the University of Washington. Eleven patients were treated with low energy neutrons alone, four received a combined photon-low energy neutron treatment regimen ("mixed beam"), and 17 were treated with high energy neutrons alone. Patients treated for microscopic residual tumor after a surgical resection were excluded from this study. With a minimum follow-up period of one year, (maximum 12 years), the overall locoregional tumor control rate for the entire series was 81%. The 5-year locoregional tumor control rate was 69%. The overall 5-year survival rate was 33% (50% for T3 tumors and 0% for T4 tumors). Compared to results obtained with conventional photon and/or electron treatment for advanced salivary gland tumors, fast neutron radiotherapy appears to offer a significant advantage.

Adult↗

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↗

Invasive bladder cancer. Strategies for cure and bladder preservation.

At the present time, standard therapy for invasive bladder cancer includes radical cystectomy and urinary diversion. Clearly, there is a population of patients who can be rendered tumor free by combinations of irradiation and chemotherapy, or irradiation and surgery. These patients may not require total cystectomy to be cured. Only time and experience will tell which treatment regimens can provide both cure and preservation of the urinary bladder.

Humans↗

Eight years experience with neutron radiotherapy in the treatment of stages C and D prostate cancer: updated results of the RTOG 7704 randomized clinical trial.

The records of 91 patients enrolled between June 1977 and April 1983 in the Radiation Therapy Oncology Group (RTOG) randomized study investigating fast neutron radiation therapy in the treatment of locally advanced prostate cancer were reviewed. Patients with stages C and D1 adenocarcinoma were randomized to receive either combined fast neutron and photon irradiation (mixed-beam) or conventional photon irradiation alone. Survival (actuarial) at eight years for the mixed-beam cohort was 63% vs 13% for the patients receiving photons alone (P = .01). Corresponding "determinental" survival rates, adjusted by exclusion of intercurrent deaths, were 82% and 54%, respectively (P = .02). Freedom from locally recurrent prostate cancer was 77% for mixed-beam patients and 31% for patients receiving photons alone (P less than .01). Analyses of outcomes accounting for all major prognostic determinants confirm the greater efficacy of mixed beam treatment with P less than .05 for survival, determinental survival, and local control.

Adenocarcinoma↗

Adjunctive hysterectomy following radiation therapy for bulky carcinoma of the uterine cervix: prognostic implications of tumor persistence.

Twenty-five patients underwent adjunctive extrafascial hysterectomy 14-60 days following completion of external and intracavitary irradiation for bulky carcinoma of the uterine cervix. Review of the operative histopathology and correlation with subsequent patient outcomes suggests that morphologically persistent cancer is prognostically ominous and that cancer near the surgical margin is viable in the majority of instances.

Adenocarcinoma↗

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↗

High dose para-aortic lymph node irradiation for gynecologic cancer: technique, toxicity, and results.

A technique for high dose (5600-6100 cGy) extended field irradiation to the para-aortic lymph nodes is described. Fourteen patients have been treated with this technique, of whom 10 have had histologic confirmation of para-aortic node metastases. With follow-up ranging from 11 to 78 months, 7 of 14 patients are alive and clinically cancer-free. Acute effects of extended field treatment on patient weight and circulating blood counts are analyzed, and late treatment morbidity assessed. The findings suggest that such treatment, executed with modern equipment and appropriate technique, is not significantly more hazardous than pelvic irradiation, and can result in a substantial probability of disease-free survival.

Adult↗

In vitro and in vivo radiation sensitization by the halogenated pyrimidine 5-chloro-2'-deoxycytidine.

5-Chloro-2'-deoxycytidine (Cld/Cyd) is hypothesized to have preferential incorporation into tumor DNA on the basis of elevated deoxycytidine-5'-phosphate deaminase and deoxycytidine kinase levels in tumors. Radiosensitization by Cld/Cyd was evaluated in exponentially growing Chinese hamster ovary cells by determining the ratio of radiation doses in control and treated cells to produce the same degree of cell killing (sensitizer enhancement ratio). Sensitizer enhancement ratios of 1.2-1.8 are seen at Cld/Cyd concentrations of 3-100 microM, 64 h incubation, and 200-600 cGy irradiation. Coincubation with tetrahydrouridine (H4Urd), a proposed inhibitor of Cld/Cyd catabolism by plasma cytidine deaminase resulted in no enhanced drug or radiation cytotoxicity. C3H mice given implants of RIF-1 tumors received 72-h continuous i.p. infusions of Cld/Cyd with or without H4Urd, or 5-bromo-2'-deoxyuridine (BrdUrd). Excised tumors were irradiated as single cell suspensions in vitro. Infusions of equimolar (0.4 mmol/kg/day) Cld/Cyd or BrdUrd resulted in greater radiosensitization by BrdUrd with no potentiation of Cld/Cyd by coinfusion with 0.8 mmol/kg/day H4Urd. Infusions with equitoxic doses of Cld/Cyd (0.8 mmol/kg/day) or BrdUrd (0.4 mmol/kg/day) yielded equal BrdUrd and Cld/Cyd sensitizer enhancement ratios of 1.6, without H4Urd potentiation of Cld/Cyd. Fluorescence-activated cell sorter analysis of tumor cell suspensions using a monoclonal antibody reactive with BrdUrd and Cld/Cyd disclosed a population of noncycling cells in tumors treated with Cld/Cyd/H4Urd that is not seen in tumors exposed to either BrdUrd or Cld/Cyd alone.

Animals↗

Lymphocyte predominant Hodgkin's disease: clinical presentation and results of treatment.

The records of 59 patients with lymphocyte predominant Hodgkin's disease (LPHD) evaluated and treated at Stanford University Medical Center between 1963 and 1983 were reviewed. Of these 59 patients, 92% are alive at 10 years following treatment, 78% are relapse-free, and none have died of Hodgkin's disease. Compared with the other histologic subtypes of Hodgkin's disease, LPHD presents more frequently as stage I or II disease (78% vs. 55%) and less frequently with constitutional symptoms (7% vs. 32%). Despite these factors, there is no statistically significant difference in either survival or freedom-from-relapse (FFR) between the histologic subtypes when comparisons are made on a stage-for-stage basis. Analysis of sites of presentation and relapse reveals that LPHD rarely involves intrathoracic structures. Patients with C.S. I disease presenting in inguinofemoral or high cervical lymph nodes do not require staging laparotomy as none of these patients were upstaged by surgery. Patients with stage I disease involving high cervical lymph nodes may be treated with limited field irradiation employing fields no more extensive than a mantle and Waldeyer's ring field, as no relapses have been seen in such patients treated in this fashion. Although limited field irradiation was used successfully for LPHD presenting in other localized sites, inadequate patient numbers preclude assessment of this treatment for those clinical presentations.

Adolescent↗

Childhood Hodgkin's disease: patterns of relapse.

One hundred seventy-nine consecutive children with Hodgkin's disease seen at Stanford University Medical Center between the years 1961-1980 have been analyzed for survival and freedom-from-relapse as a function of clinical versus laparotomy staging as well as primary treatment modalities. Of laparotomy-staged patients, 86% are alive at 10 years after primary radiation with chemotherapy reserved for relapse, as compared with 90% managed by planned combined modality therapy (p = 0.62). Patients who were clinically staged and managed with primary radiation have only a 69% survival (p = 0.05). A favorable subgroup of patients with lymphocyte-predominant Hodgkin's disease experienced a low relapse rate regardless of primary treatment modality. Patterns of relapse in clinically staged patients reflect understaging, with most relapses in distant, nonirradiated sites, whereas the less frequent relapses in laparotomy-staged patients usually reflect regional recurrence. It is concluded that laparotomy staging is highly desirable to allow greatest flexibility in optimizing individual therapy. Routine combined modality treatment for all patients would overtreat certain favorable subgroups, who can be managed more conservatively as long as the information derived from surgical staging is available. For young children, in whom bone growth issues are paramount, combined modality treatment using low-dose radiation is recommended. For older children and adolescents, where concerns over chemotherapy-related leukemogenesis and infertility are more important than height considerations, radiation alone may be used for stages I-IIIA with equal overall success.

Adolescent↗

Nutrient uptake by embryos of the Australian viviparous lizard Eulamprus tympanum.

Eulamprus tympanum is a high-altitude viviparous lizard that was probably used to help define a Type I chorioallantoic placenta. In this article, we (1) describe the net transport of nutrients across the placenta of E. tympanum, and (2) compare placental uptake in E. tympanum with a previous study of Eulamprus quoyii, which occurs in warmer environments, to assess the potential importance of thermal regime on placentotrophy. Freshly ovulated eggs are 387.3+/-19.7 mg. There is a significant net uptake of water and a net loss of dry matter during development, so the dry neonate is only 84% the size of the dry egg. There is no significant change in the total ash or nitrogen in eggs during embryonic development, with the entire loss of dry matter being lipid. Almost the entire loss of lipid occurs in the triacylglycerol fraction, with no net change in phospholipids. A net increase in total cholesterol suggests that cholesterol is synthesised by the developing embryo. The lipid profile of eggs of E. tympanum reflects that of other species with simple placentae in having a relatively high proportion of triacylglycerol and little cholesterol. The fatty acid composition of eggs reflects that expected in the diet of E. tympanum. There is a preservation and some synthesis of arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids in the phospholipid fraction during embryonic development. Despite there being no net uptake of ash, there is a net increase in calcium, potassium, sodium, and magnesium in the neonate compared with the egg. We conclude that E. tympanum, like E. quoyii, is predominantly lecithotrophic with little, if any, uptake of organic molecules but with significant uptake of some inorganic ions and water. In addition, there is no difference in placentotrophy correlated with differences in the environments inhabited by each species.

Animals↗