Optimal Cotton Insecticide Application Termination Timing: A Meta-Analysis.

The concept of insecticide termination timing is generally accepted among cotton (Gossypium hirsutum) researchers; however, exact timings are often disputed. Specifically, there is uncertainty regarding the last economic insecticide application to control fruit-feeding pests including tarnished plant bug (Lygus lineolaris (Palisot de Beauvois)), boll weevil (Anthonomus grandis), bollworm (Helicoverpa zea), tobacco budworm (Heliothis virescens), and cotton fleahopper (Pseudatomoscelis seriatus). A systematic review of prior studies was conducted within a meta-analytic framework. Nine publicly available articles were amalgamated to develop an optimal timing principle. These prior studies reported 53 independent multiple means comparison field experiments for a total of 247 trial observations. Stochastic plateau theory integrated with econometric meta-analysis methodology was applied to the meta-database to determine the shape of the functional form of both the agronomic optimal insecticide termination timing and corresponding yield potential. Results indicated that current university insecticide termination timing recommendations are later than overall estimated timing suggested. The estimated 159 heat units (HU) after the fifth position above white flower (NAWF5) was found to be statistically different than the 194 HU termination used as the status quo recommended termination timing. Insecticides applied after 159 HU may have been applied in excess, resulting in unnecessary economic and environmental costs. Empirical results also suggested that extending the insecticide termination time by one unit resulted in a cotton lint yield increase of 0.27 kilograms per hectare up to the timing where the plateau began. Based on economic analyses, profit-maximizing producers may cease application as soon as 124 HU after NAWF5. These results provided insights useful to improve production systems by applying inputs only when benefits were expected to be in excess of the respective costs.

Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. PATIENTS AND METHODS: Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0-1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. RESULTS: There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82-1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70-1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). CONCLUSIONS: Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. CLINICALTRIALSGOV: NCT01381874.

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials.

BACKGROUND: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. PATIENTS AND METHODS: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. RESULTS: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. CONCLUSION: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. CLINICAL TRIALS NUMBER: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).

Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy.

PURPOSE: To examine the efficacy of fast neutron radiotherapy for the treatment of locally advanced and/or recurrent adenoid cystic carcinoma of the head and neck and to identify prognostic variables associated with local-regional control and survival. METHODS AND MATERIALS: One hundred fifty-nine patients with nonmetastatic, previously unirradiated, locally advanced, and/or recurrent adenoid cystic carcinoma (ACC) of the head and neck region were treated with fast neutron radiotherapy during the years 1985-1997. One hundred fifty-one patients had either unresectable disease, or gross residual disease (GRD) after an attempted surgical extirpation. Eight patients had microscopic residual disease and were analyzed separately. Sixty-two percent of patients had tumors arising in minor salivary glands, 29% in major salivary glands, and 9% in other sites such as the lacrimal glands, tracheal-bronchial tree, etc. Fifty-five percent of patients were treated for postsurgical recurrent disease and 13% of patients had lymph node involvement at the time of treatment. The median duration of follow-up was 32 months (range 3-142 months). Actuarial curves for survival, cause-specific survival, local-regional control, and the development of distant metastases are presented for times out to 11 years. RESULTS: The 5-year actuarial local-regional tumor control rate for the 151 patients with GRD was 57%; the 5-year actuarial overall survival rate was 72%; and the 5-year actuarial cause-specific survival rate was 77%. Variables associated with decreased local-regional control in the patients with GRD as determined by multivariate analysis included base of skull involvement (p < 0.01) and biopsy only versus an attempted surgical resection prior to treatment (p = 0.03). Patients without these negative factors had an actuarial local-regional control rate of 80% at 5 years. Patients with microscopic residual disease (n = 8) had a 5-year actuarial local-regional control rate of 100%. Base of skull involvement (p < 0.001), lymph node metastases at the time of treatment (p < 0.01), biopsy only prior to neutron radiotherapy (p = 0.03), and recurrent tumors (p = 0.04) were found to be associated with a diminished cause-specific survival as ascertained by multivariate analysis. Patients with base of skull involvement and positive lymph nodes at presentation had an increased rate of the development of distant metastases at 5 years, (p < 0.01 and p < 0.001, respectively). No statistical difference in outcome was observed between major and minor salivary gland sites. CONCLUSIONS: Fast neutron radiotherapy is an effective treatment for locally advanced ACC of the head and neck region with acceptable toxicity. Further improvements in local-regional control are not likely to impact survival until more effective systemic agents are developed to prevent and/or treat distant metastatic disease.

Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors.

BACKGROUND: Malignant salivary gland tumors are rare tumors of the head and neck region. The treatment of these tumors has generally consisted of surgical extirpation, with postoperative radiotherapy improving locoregional control and survival in patients with high risk tumors. Neutron radiotherapy has been found to be more efficacious than conventional radiotherapy in the setting of inoperable or subtotally resected salivary gland tumors. METHODS: One hundred forty-eight patients with malignant salivary tumors of major salivary gland origin were treated at the University of Washington Medical Center with fast neutron radiotherapy between the years 1984 and 1995. One hundred twenty-eight patients were treated with curative intent, and of these, 120 patients had evidence of gross residual disease at the time of treatment. These patients constitute the main analysis of this paper. Of these patients, 19% had recurrent disease, 39% were initially seen with positive lymph nodes, and 11% had previously received full dose conventional radiotherapy. At the time of analysis, the median period at risk of survivors was 26 months. RESULTS: The 5-year actuarial locoregional control rate for all patients with gross tumor treated with curative intent was 59%. A tumor size < or =4 cm was associated with an excellent locoregional control rate (80%), and cause-specific survival (73%) at 5 years compared with patients with larger tumors (35% and 22%, respectively, p<.001 in both cases). On univariate analysis, there appeared to be an advantage in locoregional control for patients with smaller sized tumors (< or =4 cm) who underwent an attempted surgical extirpation. Locoregional control was excellent (100%) in patients having a complete surgical resection of their tumors and undergoing postoperative neutron radiotherapy because of the presence of other high risk factors. Lymph node status at the time of treatment, base of skull involvement, and male sex were associated with the development of distant metastasis, with 52% of node positive patients developing distant metastases by 5 years, compared with 32% of node negative patients (p = .04). CONCLUSIONS: Neutron radiotherapy is an effective form of treatment for patients with high risk, locally advanced tumors of major salivary gland origin. An initial surgical resection appears beneficial in patients for whom such an approach is feasible.

Reduction of radioactive seed embolization to the lung following prostate brachytherapy.

PURPOSE: Ultrasound-guided interstitial implantation of radioactive seeds is a common treatment for early stage prostate cancer. One of the risks associated with this therapy is seed embolization to the lung. This paper reports on the incidence and possible adverse effects of seed migration. METHODS AND MATERIALS: Two hundred ninety consecutive patients were treated with permanent radioactive seed brachytherapy for prostate cancer between January 1 and December 31, 1995. One hundred fifty-four patients were treated with iodine-125 (I-125), and 136 patients were treated with palladium-103 (Pd-103). All but one patient had a routine post implant chest radiograph (CXR), leaving 289 evaluable patients. RESULTS: Twenty radioactive seed pulmonary emboli were identified in 17 patients; 3 patients had two emboli each. The radioactive seed pulmonary embolism rate for the entire group of patients was 5.9%. Acute pulmonary symptoms were not reported by any patient in this series. One hundred forty-six study patients were implanted with free seeds alone (136 Pd-103 and 11 I-125), and 143 were implanted with linked seed embedded in a vicryl suture for the peripheral portions of their implants. The radioactive seed embolization rate by patient was 11% (16/146) versus 0.7% (1/143) for free seed implants and implants utilizing linked seeds, respectively. The difference was statistically significant, p = 0.0002. No patient had detectable morbidity as a consequence of seed emboli. CONCLUSION: The use of linked seeds embedded in vicryl sutures for the peripheral portion of permanent radioactive seed prostate implants significantly reduced the incidence of pulmonary seed embolization in patients treated with the Seattle technique.

Digital radiotherapy simulator.

We describe a prototype digital radiotherapy simulator which consists of a conventional simulator gantry, digital spot imager, and image correction and reconstruction software. The ability of the digital spot imager to acquire a diagnostic quality image directly in digital format during simulation offers unique possibilities in clinical practice. Applications include prescription of multileaf collimator, on-line patient setup verification, remote consultation and treatment planning. In addition, we discuss the possibility of using the digital simulator as a volume-CT scanner capable of obtaining three-dimensional anatomical information in a single scan.

Fast neutrons in prostatic adenocarcinomas: worldwide clinical experience.

Primary tumor control remains a major problem in the treatment of locally advanced prostate carcinoma. Clinical local failure rates approach 30-40% and may be significantly higher when results of prostatic biopsy or prostate-specific antigen (PSA) levels are considered. The low growth rate and cycling fraction of prostate adenocarcinoma suggest potential therapeutic advantage for the high linear energy transfer (LET) of neutrons. The Radiation Therapy Oncology Group (RTOG) performed a multi-institutional randomized trial (RTOG 77-04) comparing mixed beam (neutron plus photon) irradiation to conventional photon irradiation for the treatment of locally advanced prostate cancer. A subsequent trial by the Neutron Therapy Collaborative Working Group (NTCWG 85-23) compared pure neutron irradiation to standard photon irradiation. Both randomized trials demonstrate significant improvement in locoregional control with neutron irradiation compared to conventional photon irradiation in the treatment of locally advanced prostate carcinoma. To date, only the mixed beam trial has shown a significant survival benefit. Future analysis of the larger NTCWG trial at the 10-year point should confirm whether or not improved locoregional control translates into a survival advantage. These findings have significant implications for all local treatment strategies including dose-escalated conformal photon irradiation, prostate implantation, and neutron radiation. Given the large numbers of patients afflicted with this disease, a positive survival advantage for neutrons or mixed beam therapy would provide a strong incentive for the development of economically feasible clinical neutron facilities.

Boron neutron capture enhanced fast neutron radiotherapy for malignant gliomas and other tumors.

Both fast neutron radiotherapy and boron neutron capture therapy have been investigated as new radiation treatment techniques for patients with malignant gliomas. While each of these techniques individually has shown the potential for pathological eradication of malignant glioma, to date neither has evolved into an accepted, improved method of treatment. We have recently begun a research program investigating the feasibility of combining the benefits of both types of therapy. As a fast neutron beam penetrates tissue some of the particles are degraded to thermal energies. These can be captured by 10B or other suitable isotopes resulting in a highly-localized release of additional energy during a course of fast neutron radiotherapy. In this article we will review the rationale for such an approach, and review the underlying physics as well as in vitro, in vivo, and early human studies testing its feasibility. If appropriate carrier agents can be found that preferentially-localize in tumor cells, this approach ena be applied to many different tumor systems.

Corpus callosum involvement as a prognostic factor for patients with high-grade astrocytoma.

PURPOSE: To evaluate corpus callosum involvement as a prognostic factor for patients with high-grade astrocytoma. METHODS: From 1986 through 1994, 141 adult patients with Karnofsky performance status (KPS) > or = 40 underwent primary treatment for anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) at the University of Washington Medical Center. Preoperative magnetic resonance imaging and/or computed tomography to assess corpus callosum involvement was available for 105 of these patients. Corpus callosum involvement was evaluated as a prognostic factor for survival using recursive partitioning analysis and multivariate analysis with a Cox proportional hazards model. RESULTS: For the 105 patients evaluable for corpus callosum involvement, the median and 2-year survival were 59 weeks and 28%, respectively. On multivariate analysis, the only independent prognostic factors were KPS (p = 0.0001) and histology (p = 0.042). On recursive partitioning analysis, the first significant split occurred at KPS < 70 vs. KPS > or = 70. Patients with KPS > or = 70 were split by age (< 50 years vs. > or = 50 years), with those younger than 50 years further split by absence or presence of corpus callosum involvement. Among patients with KPS > or = 70 and age < 50 years, median survival was 57 weeks if the corpus callosum was involved (35% 2-year survival) and 105 weeks if the corpus callosum was not involved (56% 2-year survival). CONCLUSION: Corpus callosum involvement based on preoperative imaging is an unfavorable prognostic factor for survival among the subgroup of young, good-performance-status patients with high-grade astrocytoma.

The potential role of external beam radiation in preventing restenosis after coronary angioplasty.

The potential role of radiation in the prevention of coronary artery restenosis after angioplasty has generated much recent interest. Animal research and pilot clinical efforts have focused primarily on intraluminal methods of radiation delivery. This article reviews the experience to date with external beam radiation in restenosis prevention and suggests issues that should be considered from the standpoint of both external beam and intravascular radiotherapy. External beam radiation can certainly play an effective role in clinical studies of coronary artery restenosis, and a multicenter randomized trial of external beam radiation after coronary angioplasty has been initiated.

Neutron radiotherapy for adenoid cystic carcinoma of minor salivary glands.

PURPOSE: To examine the efficacy of fast neutron radiotherapy for the treatment of patients with locally advanced, adenoid cystic carcinoma of minor salivary glands and to identify prognostic variables associated with local control, overall survival, and cause specific survival. METHODS AND MATERIALS: Eighty-four patients having adenoid cystic carcinoma of minor salivary glands were treated with fast neutron radiotherapy during the years 1985-1994. All patients had either unresectable disease or gross disease remaining after attempted surgical extirpation. Seventeen patients had previously received conventional radiotherapy and their subsequent treatment fields and doses for neutron radiotherapy were modified for critical sites (brainstem, spinal cord, brain). Although the median doses (tumor maximum and tumor minimum) only varied by < or = 10%, treatment portals were substantially smaller in these patients because of normal tissue complication considerations. Twelve patients (13%) had distant metastases at the time of treatment and were only treated palliatively with smaller treatment portals and lower median tumor doses (< or = 80% of the doses delivered to curatively treated patients). Seventy-two patients were treated with curative intent, with nine of these having recurrent tumors after prior full-dose radiotherapy. The median duration of follow-up at the time of analysis was 31.5 months (range 3-115). Sites of disease and number of patients treated per disease site were as follows: paranasal sinus-31; oral cavity-20; oropharynx-12; nasopharynx-11; trachea-6; and other sites in the head and neck-4. RESULTS: The 5-year actuarial local-regional tumor control rate for all patients treated with curative intent was 47%. Patients without involvement of the cavernous sinus, base of skull, or nasopharynx (51 patients) had a 5-year actuarial local-regional control rate of 59%, whereas local-regional control was significantly lower (15%) for patients with tumors involving these sites (p < 0.005). In the latter cases, normal tissue injury considerations precluded delivery of the full dose to the entire tumor. Patients with no history of prior radiotherapy (63 patients) had an actuarial local control rate of 57% at 5 years compared to 18% for those (9 patients) who had been previously irradiated with conventional photons (p = 0.018). Eliminating the dose-limiting factors of prior radiation therapy and/or high risk sites of involvement, the 5-year actuarial local-regional control rate for these 46 patients was 63%, with an actuarial cause specific survival rate of 79%. Lymph node status was a predictor of distant metastasis: 57% of node positive patients developed distant metastases by 5 years compared to 15% of patients with negative nodes (p < 0.0005), and patients who had nodal involvement developed distant metastases sooner than node negative patients (p < 0.0001). The 5-year actuarial overall survival and cause specific survival for the 72 patients treated with curative intent were 59% and 64%, respectively. CONCLUSIONS: Fast neutron radiotherapy offers high local-regional control and survival rates for patients with locally advanced, unresectable adenoid cystic carcinomas of minor salivary glands. It should be considered as initial primary treatment for these patients, as well as for other patients in whom surgical extirpation would cause considerable morbidity.

Operation and permanent low activity 125I brachytheraphy for recurrent high-grade astrocytomas.

Twenty-two adult patients with recurrent high grade astrocytomas [18 glioblastoma multiforme (GBM) and 4 anaplastic astrocytoma (AA) at time of implant] underwent therapy at the University of Washington from October 1991 through March 1995, with repeat craniotomy, maximal debulking of tumor, and placement of permanent low activity 125I seeds. Median age was 41 years and median Karnofsky performance status was 90. Median survival for the entire group was 65 weeks from the time of implant. For the subgroup of GBM patients, median survival was 64 weeks from the time of implant. One-year survival from the date of implant was 57% for the entire group and 59% for those with GBM. The site of first failure after implant was local (within 2 cm of the resection cavity) in 70%, distant (noncontiguous, beyond 2 cm) in 18% and concurrently local and distant in 12%. There was one case of symptomatic radiation injury that resolved with steroid therapy, and no patient required repeat craniotomy for parenchymal necrosis. For patients with recurrent GBM, treatment with resection and permanent low activity 125I brachytherapy yielded improved survival compared to an internal historical control group treated with resection and chemotherapy (p = 0.023). Craniotomy with maximal tumor debulking and placement of low activity 125I seeds yields encouraging results with minimal morbidity in patients with recurrent high-grade astrocytomas.

Effect of high-dose pentoxifylline on acute radiation-induced lung toxicity in a rat lung perfusion model.

PURPOSE: The purpose of this study was to study the effect of high-dose oral pentoxifylline on radiation-induced acute lung injury as assessed with a rat lung perfusion model. METHODS AND MATERIALS: Adult male Sprague-Dawley rats were used throughout this study. A preliminary experiment determined that treatment with 2 g/liter pentoxifylline in drinking water resulted in an average consumption of 1.38 g/m2/day, which is comparable to the maximum tolerated dosage in humans. Seventy-two rats were irradiated to the left hemithorax with single fraction doses ranging from 10 through 18 Gy. Half were treated with 2 g/liter pentoxifylline in drinking water from 1 week before radiation through 8 weeks after radiation. Lung vascular perfusion scanning was performed at 3, 4, 5, 6, and 8 weeks after radiation using 99mTc-macroaggregated albumin. The lung perfusion ratio was defined as the number of counts due to radioactivity within the irradiated left lung region of interest divided by the number of counts within the region of the nonirradiated right lung. This lung perfusion ratio has been shown to decrease with radiation-induced lung injury. RESULTS: Although radiation led to a decreased lung perfusion ratio in all groups, those receiving pentoxifylline maintained higher ratios than irradiated controls from 3-5 weeks, especially for those receiving 15 or 18 Gy. However, from 6 through 8 weeks the irradiated controls exhibited partial recovery of lung perfusion ratio, whereas the pentoxifylline groups did not. By 8 weeks after 15 and 18 Gy, lung perfusion ratios were significantly higher for the irradiated controls than for pentoxifylline-treated rats-a reversal of the pattern observed at 3-5 weeks. CONCLUSIONS: The protection by pentoxifylline against radiation-induced acute lung injury was transient and limited to the first 5 weeks after radiation. Subsequent recovery from lung injury was inhibited by this drug at later times within the acute phase.

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.

Fast neutron radiotherapy and boron neutron capture therapy: application to a human melanoma test system.

Fast neutron radiotherapy has proven to be an effective form of treatment in a selected subset of tumors (salivary gland tumors, sarcomas, and locally-advanced prostate cancer), but has not proven to be more beneficial than conventional photon irradiation for the majority of tumor types upon which it has been tested. Normal tissue tolerance limits preclude simply further escalating the neutron dose. Boron neutron capture (BNC) provides a way of selectively augmenting the radiation dose to the tumor. This process is described, and cell culture and animal model data reviewed. An irradiation configuration was developed where an enhancement of 2.10(-3) for 1 microgram of 10B per gram of tissue was achieved. This is similar to the enhancement achievable in the center of a 20 x 20 cm field envisioned for future applications such as metastases in the brain. A boron concentration of 50 micrograms per gram of tumor tissue leads to a 10% increase in the delivered physical dose in this scenario. The first human test of BNC enhancement of a fast neutron radiotherapy beam using pharmacologically-acceptable doses of orally-administered, 10B-enriched, L-paraboronophenylalanine is reported. An enhancement of tumor response was demonstrated for a melanoma skin nodule test system. Boron levels achieved in blood, skin, and tumors are presented. Future research plans are discussed.

Cone-beam CT for radiotherapy applications.

Clinical implementation of cone-beam tomography has been hampered by the lack of two-dimensional electronic x-ray detectors that can encompass the full width of the body. We encountered the undersized detector problem in our development of a cone-beam CT system for radiotherapy applications. In order to mitigate the problem, we developed an algorithm which permits an increased reconstruction volume to be imaged using a detector of a given size. We describe the algorithm and report on its implementation using a radiotherapy simulator configured with a digital fluorography unit.

Transferrin receptor expression in nonsmall cell lung cancer. Histopathologic and clinical correlates.

BACKGROUND: In the search for tumor-related antigens with survival-predictive value, previous studies have yielded varied conclusions regarding the expression of one such antigen, the transferrin receptor in lung cancer. The goal of this study was to define the frequency of expression of transferrin receptor in lung cancer specimens and gather preliminary data regarding the prognostic value of this tumor-related antigen. METHODS: Tissue immunoreactivity was studied with a murine monoclonal antibody to transferrin receptor in patients with nonsmall cell lung cancer who underwent surgical resection at the Medical Center Hospital of Vermont during the period from January, 1988, to May, 1991. RESULTS: The study group consisted of 32 patients (21 males and 11 females) with an average follow-up length of 27 months (standard deviation of 16 months). There were 17 patients with adenocarcinoma, 14 with squamous cell carcinoma, and 1 with large cell carcinoma. At the end of data accumulation, a total of 16 deaths had been recorded (8 with squamous cell, 8 with adenocarcinoma). Normal lung tissue did not stain for transferrin receptor; however, 13 of 17 (76%) adenocarcinomas, 13 of 14 (93%) squamous cell carcinomas, and the 1 large cell carcinoma stained positively for transferrin receptor. Staining for transferrin receptor was graded according to pattern and intensity and categorized as absent-weak or strong. Survival analysis was performed to evaluate patient outcome based on a variety of clinical and experimentally determined characteristics. Groups based on N-status (N0 vs. N1 + N2, P = 0.08), stage (Stage 1 vs. Stage 2 + 3 P = 0.13), age (younger than 60 vs. 60 years or older, P = 0.09), and transferrin receptor staining (absent-weak vs. strong, P = 0.14) achieved nearly significant differences in survival. Further analysis of the differences in survival for groupings based on transferrin receptor staining found that these differences in survival reached significance for patients with larger tumors (T2 or T3, P = 0.02). CONCLUSIONS: Transferrin receptor is expressed in the majority of lung cancers and the presence of transferrin receptor in nonsmall cell lung cancers may be an indicator of poorer prognosis in certain groups of patients.