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Craig W Stevens

Publications and source records attributed to Craig W Stevens.

At least 37 records · Page 2Linked to original sources
PubMed2004

Quality assurance evaluation of delivery of respiratory-gated treatments.

We describe a method for evaluating the quality of respiratory-gated radiation delivery using a commercially available device. During irradiation, gating traces for one field for each treatment were extracted from the system for each of 14 patients. The data were then transferred to a spreadsheet. Software was developed to evaluate the following parameters: duty cycle, amplitude of fiducial motion, fraction of amplitude of motion during gated delivery, and respiratory cycle time. Criteria were established for acceptability of gating traces. In our sample, over 85% of the traces indicated acceptability. An example of results for one patient extracted from analyzed gating traces is as follows: mean duty cycle, 57%, average amplitude of motion, 0.89 cm, average fraction of motion during gated delivery, 0.45; mean respiratory cycle time, 4.5 s. This technique can be used to evaluate delivery of respiratory-gated radiation therapy for quality assurance purposes and to assess various techniques for improving delivery of gated therapy. A hardcopy of the gating traces can be used to document gated treatment delivery for potential billing of the gated delivery process.

Artifacts↗
PubMed2004

Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial.

PURPOSE: To determine the ability of amifostine to reduce the severity and/or incidence of the acute toxicities of concurrent chemotherapy and radiotherapy (RT) for non-small-cell lung cancer. METHODS AND MATERIALS: Patients with inoperable, nonmetastatic non-small-cell lung cancer receiving concurrent chemoradiotherapy were randomized to one of two treatment groups. Arm 1 patients received thoracic RT (total dose, 69.6 Gy in 58 fractions of 1.2 Gy b.i.d. 5 d/wk), plus oral etoposide (50 mg b.i.d. 30 min before thoracic RT for 10 days, repeated on Day 29) and cisplatin (50 mg/m2 i.v. on Days 1, 8, 29, and 36). Arm 2 patients received the same treatment plus amifostine (500 mg i.v. 20-30 min before any treatment the first 2 days of each week). Acute effects were assessed using the National Cancer Institute Common Toxicity Criteria. RESULTS: Sixty-two patients were enrolled between November 1998 and January 2001. The minimal follow-up was 24 months, and the median follow-up of living patients was 31 months. The patient and tumor characteristics were equally distributed between the patients in the two arms. The median survival time was 20 months in Arm 1 patients and 19 months in Arm 2 patients. The maximal esophageal toxicity was mild (Grade 1) in 23%, moderate (Grade 2) in 42%, and severe (Grade 3-4) in 35% of patients in Arm 1; the corresponding rates for the Arm 2 patients were 48%, 35%, and 16% (p = 0.021). Severe pneumonitis occurred in 16% of the Arm 1 and none of the Arm 2 patients (p = 0.020, chi-square test). Neutropenic fever occurred in 39% of Arm 1 and 16% of Arm 2 patients (p = 0.046, chi-square test). Mild hypotension, dysgeusia, and sneezing were significantly more frequent among the patients in Arm 2. CONCLUSION: Amifostine reduced the severity and incidence of acute esophageal, pulmonary, and hematologic toxicity resulting from concurrent cisplatin-based chemotherapy and RT. Amifostine had no apparent effect on survival in these patients with unresectable non-small-cell lung cancer, suggesting that it does not have a tumor-protective effect.

Adult↗
PubMed2004

Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.

PURPOSE: To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. METHODS AND MATERIALS: A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. RESULTS: Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. CONCLUSION: It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Comparative measurements of hypoxia in human brain tumors using needle electrodes and EF5 binding.

Hypoxia is known to be an important prognostic marker in many human cancers. We report the use of two oxygen measurement techniques in human brain tumors and compare these data with semiquantitative histological end points. Oxygenation was measured using the Eppendorf needle electrode and/or EF5 binding in 28 brain tumors. These data were compared with necrosis, mitosis, and endothelial proliferation. In some tumors, absolute EF5 binding was converted to tissue pO(2) based on in vitro calibrations. Eppendorf electrode readings could not be used to identify WHO grade 1/2 versus WHO grade 3/4 tumors, they could not differentiate grade 3 versus grade 4 glial-derived neoplasms, nor did they correlate with necrosis or endothelial proliferation scores. EF5 binding increased as the tumor grade increased and was significantly associated with necrosis and endothelial proliferation. There was no statistically significant correlation between the two hypoxia detection techniques, although both methods indicated similar absolute ranges of tissue pO(2). There was substantial inter- and intratumoral heterogeneity of EF5 binding in WHO grade 4 glial neoplasms. The majority of cells in glial-derived tumor had levels of hypoxia that were mild to moderate (defined herein as 10% to 0.5% pO(2)) rather than severe (defined as approximately 0.1% pO(2)). Immunohistochemical detection of EF5 binding tracks histological parameters in adult brain tumors, with increased binding associated with increasing necrosis and endothelial proliferation. The proportion of moderately to severely hypoxic cells is relatively low, even in the high-grade tumors. Human brain tumors are dominated by oxic to moderately hypoxic cells.

Adult↗
PubMed2004

Predicting radiosensitivity using DNA end-binding complex analysis.

Previous reports have suggested that measuring radiosensitivity of normal and tumor cells would have significant clinical relevance for the practice of radiation oncology. We hypothesized that radiosensitivity might be predicted by analyzing DNA end-binding complexes (DNA-EBCs), which form at DNA double-strand breaks, the most important cytotoxic lesion caused by radiation. To test this hypothesis, the DNA-EBC pattern of 21 primary human fibroblast cultures and 15 tumor cell lines were studied. DNA-EBC patterns were determined using a modified electrophoretic mobility shift assay and were correlated with radiosensitivity, as measured by SF2. DNA-EBC analysis identified a rapidly migrating ATM-containing band (identified as "band-A") of which the density correlated with SF2 (0.02 </= SF2 </= 0.41) in primary fibroblasts (r(2) = 0.77). The DNA-EBC pattern of peripheral blood lymphocytes was identical to that of fibroblasts. In addition, band-A density correlated with SF2 (0.35 </= SF2 </= 0.80) in 15 human tumor cell lines (r(2) = 0.91). Densitometry of other bands, or total DNA-EBC binding, correlated more poorly with SF2 (r(2) < 0.45). These data indicate that DNA-EBC analysis may be a practical, clinically relevant predictor of tumor and primary cell radiosensitivity.

Cell Line↗
PubMed2004

Dosimetric benefits of respiratory gating: a preliminary study.

In this study, we compared the amount of lung tissue irradiated when respiratory gating was imposed during expiration with the amount of lung tissue irradiated when gating was imposed during inspiration. Our hypothesis was that the amount of lung tissue spared increased as inspiration increased. Computed tomography (CT) image data sets were acquired for 10 patients who had been diagnosed with primary bronchogenic carcinoma. Data sets were acquired during free breathing and during breath-holds at 0% tidal volume and 100% tidal volume, and, when possible, at deep inspiration, corresponding to approximately 60% vital capacity. Two treatment plans were developed on the basis of each of the gated data sets: one in which the treatment portals were those of the free-breathing plan, and the other in which the treatment portals were based on the gated planning target volumes. Dose-mass histograms of the lungs calculated at 0% tidal volume were compared to those calculated at deep inspiration and at 100% tidal volume. Data extracted from the dose-mass histograms were used to determine the most dosimetrically beneficial point to gate, the reduction in the amount of irradiated lung tissue that resulted from gating, and any disease characteristics that might predict a greater need for gating. The data showed a reduction in the mass of normal tissue irradiated when treatment portals based on the gated planning target volume were used. More normal lung tissue was spared at deep inspiration than at the other two gating points for all patients, but normal lung tissue was spared at every point in the respiratory cycle. No significant differences in the amount of irradiated tissue by disease characteristic were identified. Respiratory gating of thoracic radiation treatments can often improve the quality of the treatment plan, but it may not be possible to determine which patients may benefit from gating prior to performing the actual treatment planning.

Artifacts↗
PubMed2004

Opioid research in amphibians: an alternative pain model yielding insights on the evolution of opioid receptors.

This review summarizes the work from our laboratory investigating mechanisms of opioid analgesia using the Northern grass frog, Rana pipiens. Over the last dozen years, we have accumulated data on the characterization of behavioral effects after opioid administration on radioligand binding by using opioid agonist and antagonist ligands in amphibian brain and spinal cord homogenates, and by cloning and sequencing opioid-like receptor cDNA from amphibian central nervous system (CNS) tissues. The relative analgesic potency of mu, delta, and kappa opioids is highly correlated between frogs and other mammals, including humans. Radioligand binding studies using selective opioid agonists show a similar selectivity profile in amphibians and mammals. In contrast, opioid antagonists that are highly selective for mammalian mu, delta, and kappa opioid receptors were not selective in behavioral and binding studies in amphibians. Three opioid-like receptor cDNAs were cloned and sequenced from amphibian brain tissues and are orthologs to mammalian mu, delta, and kappa opioid receptors. Bioinformatics analysis of the three types of opioid receptor cDNAs from all vertebrate species with full datasets gave a pattern of the molecular evolution of opioid receptors marked by the divergence of mu, delta, and kappa opioid receptor sequences during vertebrate evolution. This divergence in receptor amino acid sequence in later-evolved vertebrates underlies the hypothesis that opioid receptors are more type-selective in mammals than in nonmammalian vertebrates. The apparent order of receptor type evolution is kappa, then delta, and, most recently, the mu opioid receptor. Finally, novel bioinformatics analyses suggest that conserved extracellular receptor domains determine the type selectivity of vertebrate opioid receptors.

Amphibians↗
PubMed2004

Radiosensitivity is predicted by DNA end-binding complex density, but not by nuclear levels of band components.

BACKGROUND AND PURPOSE: We previously determined that the density of a rapidly migrating DNA end-binding complex (termed 'band-A') predicts radiosensitivity of human normal and tumor cells. The goal of this study was first to identify the protein components of band-A and to determine if the protein levels of band-A components would correlate with band-A density and radiosensitivity. PATIENTS AND METHODS: DNA end-binding protein complex (DNA-EBC) protein components were identified by adding antibodies specific for a variety of DNA repair-associated proteins to the DNA-EBC reaction and then noting which antibodies super-shifted various DNA-EBC bands. Band-A levels were correlated with SF2 for a panel of primary human fibroblasts heterozygous for sequence-proven mutations in BRCA1 or BRCA2. The nuclear protein levels of band-A components were determined in each BRCA1 heterozygote by western hybridization. RESULTS: DNA-EBC analysis of human nuclear proteins revealed 10 identifiable bands. The density of the most rapidly migrating DNA-EBC band correlated closely with both BRCA-mutation status and radiosensitivity (r(2)=0.85). This band was absent in cells with homozygous mutations in their ataxia-telangiectasia-mutated protein (ATM) genes. This band was also completely supershifted by the addition of antibodies to ATM, Ku70, DNA ligase III, Rpa32, Rpa14, DNA ligase IV, XRCC4, WRN, BLM, RAD51 and p53. However, the intranuclear concentrations of these proteins did not correlate with either the SF2 or DNA-EBC density. Neither BRCA1 or BRCA2 could be detected in band-A. CONCLUSIONS: DNA-EBC analysis of human nuclear extracts resulted in 10 bands, at least six of which contained ATM. The density of one of the DNA-EBCs predicted the radiosensitization caused by BRCA haploinsufficiency, and this band contains Ku70, ATM, DNA ligase III, Rpa32, Rpa14, DNA ligase IV, XRCC4, WRN, BLM, RAD51 and p53 but not BRCA 1 or 2. The density of band-A was independent of the nuclear concentration of any of its known component.

BRCA1 Protein↗
PubMed2004

Endoscopic ultrasound after preoperative chemoradiation can help identify patients who benefit maximally after surgical esophageal resection.

BACKGROUND: We investigated whether differences in postoperative survival exist based on the presence and site of residual tumor (esophagus vs regional lymph nodes) after preoperative chemoXRT in patients with esophageal cancer. Based on these data, we reevaluated the role of EUS in identifying patients who maximally benefit from surgical esophageal resection after preoperative chemoXRT. METHODS: We studied 97 consecutive esophageal cancer patients treated with preoperative chemoXRT and a potentially curative surgical procedure between 1998 to 2001. All patients had EUS examination prior to chemoXRT and 53 had a repeat EUS examination after chemoXRT but prior to surgery. Surgical resection specimens were analyzed for absence or presence of residual tumor and its location. RESULTS: Patients with residual tumor in the esophagus (pathT1-3N0) and patients without residual tumor (pathT0N0) had similar cumulative survival (p= 0.92). Patients with residual cancer in lymph nodes showed a trend toward shorter cumulative survival compared to patients without residual tumor in lymph nodes (p= 0.086). The actuarial survival in pathN1 group was lower than pathN0 group at 1, 2, and 3 yr. Patients with significant residual lymphadenopathy detected by EUS after therapy had significantly worse postoperative survival compared to patients with no residual lymphadenopathy (p= 0.028). In eight patients, we found that reliable cytologic identification of residual malignancy was technically feasible by EUS-FNA after chemoradiation therapy. CONCLUSIONS: Following preoperative chemoXRT and surgery, patients with residual tumor in the regional lymph nodes have lower actuarial survival at 1, 2, and 3 yr after surgery, compared to patients with path CR or with residual tumor only in the esophagus. EUS and EUS-guided FNA can be helpful in identifying residual tumor in the lymph nodes after preoperative chemoXRT to select patients who benefit maximally from surgery.

Adenocarcinoma↗
PubMed2004

A deformable-model approach to semi-automatic segmentation of CT images demonstrated by application to the spinal canal.

Because of the importance of accurately defining the target in radiation treatment planning, we have developed a deformable-template algorithm for the semi-automatic delineation of normal tissue structures on computed tomography (CT) images. We illustrate the method by applying it to the spinal canal. Segmentation is performed in three steps: (a) partial delineation of the anatomic structure is obtained by wavelet-based edge detection; (b) a deformable-model template is fitted to the edge set by chamfer matching; and (c) the template is relaxed away from its original shape into its final position. Appropriately chosen ranges for the model parameters limit the deformations of the template, accounting for interpatient variability. Our approach differs from those used in other deformable models in that it does not inherently require the modeling of forces. Instead, the spinal canal was modeled using Fourier descriptors derived from four sets of manually drawn contours. Segmentation was carried out, without manual intervention, on five CT data sets and the algorithm's performance was judged subjectively by two radiation oncologists. Two assessments were considered: in the first, segmentation on a random selection of 100 axial CT images was compared with the corresponding contours drawn manually by one of six dosimetrists, also chosen randomly; in the second assessment, the segmentation of each image in the five evaluable CT sets (a total of 557 axial images) was rated as either successful, unsuccessful, or requiring further editing. Contours generated by the algorithm were more likely than manually drawn contours to be considered acceptable by the oncologists. The mean proportions of acceptable contours were 93% (automatic) and 69% (manual). Automatic delineation of the spinal canal was deemed to be successful on 91% of the images, unsuccessful on 2% of the images, and requiring further editing on 7% of the images. Our deformable template algorithm thus gives a robust segmentation of the spinal canal on CT images. The method can be extended to other structures, although it remains to be shown that chamfer matching is sufficiently robust for the delineation of soft-tissue structures surrounded by soft tissue.

Algorithms↗
PubMed2003

Treatment planning for lung cancer: traditional homogeneous point-dose prescription compared with heterogeneity-corrected dose-volume prescription.

PURPOSE: To quantify the differences in doses to target volumes and critical thoracic structures calculated by traditional homogeneous point-dose prescription and heterogeneity-corrected volume-dose prescription. METHODS AND MATERIALS: Between 1998 and 2001, 30 patients with inoperable Stage I/II non-small-cell lung cancer underwent radiation treatment planning at our institution. A commercially available convolution/superposition- based algorithm was used. Three treatment plans were calculated for each patient using identical beam geometries: one plan was generated by traditional homogeneous point-dose prescription, a second by the traditional method with heterogeneity correction, and a third by heterogeneity-corrected volume-dose prescription that would cover 95% of the planned target volume (PTV). Target volume coverage, isocenter dose, and dose uniformity in the second and third plans were compared. RESULTS: The PTV, clinical target volume (CTV), and isocenter calculated by the heterogeneity-corrected volume-dose method were equivalent to those calculated by the traditional homogeneous point-dose method with heterogeneity correction. The fraction of the PTV covered by heterogeneity-corrected volume-dose prescription was significantly greater than the fraction covered by traditional homogeneous point-dose prescription with heterogeneity correction (p = 0.05). The dose prescribed using the traditional method would have been delivered to less than 90% of the PTV in 14 of 30 patients. There was no significant difference in the maximum and minimum doses to the PTV, the CTV, or the isocenter calculated by the traditional homogeneous method with heterogeneity correction and the heterogeneity-corrected volume-dose method. There was also no significant difference in the planned volume of lung receiving greater than 20 Gy as calculated by these two methods. CONCLUSION: When compared with traditional homogeneous radiation treatment planning, heterogeneity-corrected methods produce equivalent PTV, CTV, and isocenter doses while providing superior PTV coverage.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Effects of radiotherapy and chemotherapy on lung function in patients with non-small-cell lung cancer.

PURPOSE: To evaluate the effects of chemoradiation on objective tests of pulmonary function. MATERIALS AND METHODS: One hundred lung cancer patients treated in five protocols between 1992 and 2000 with combinations of thoracic radiotherapy (RT) and chemotherapy were evaluated with pre- and post-RT pulmonary function tests. The pulmonary function tests were analyzed for changes in measures of obstruction (forced expiratory volume in 1 s per unit of vital capacity [FEV(1)/VC]), restriction (total lung capacity [TLC]), and diffusing capacity (diffusing capacity for carbon monoxide [DLCO]). The use and timing of chemotherapy and RT, as well as patient, tumor, and treatment factors, were evaluated using univariate and multivariate analyses. RESULTS: No treatment or patient factors were significantly associated with changes in FEV(1)/VC. Chemotherapy with RT, compared with RT alone, was associated with a lower post-RT TLC (92% vs. 107%, p = 0.002). Nodal status (N2-N3 vs. N1), tumor location (central vs. peripheral), use of >/=6 treatment fields, and tumor volume >/=100 cm(3) were also associated with a significantly lower post-RT TLC. On univariate analysis, the use of any chemotherapy (p = 0.029) and the use of concurrent vs. sequential chemotherapy (p = 0.028) were predictive of a lower post-RT DLCO. Patient age >/=60 years, nodal status (N2-N3 vs. N0-N1), tumor volume >/=100 cm(3), tumor location (central vs. peripheral), and use of >/=6 treatment fields were also associated with a significantly lower post-RT DLCO. The fractional volume of irradiated normal lung correlated with the decrease in DLCO (p <0.001), with a 1.3% DLCO decline for each 1% of total lung volume that received >20 Gy. CONCLUSIONS: The addition of chemotherapy to RT significantly exacerbates the post-RT decrease in TLC and DLCO. The greatest decrease in DLCO occurs in patients treated with concurrent chemoradiation.

Adult↗
PubMed2003

Intensity-modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesothelioma: clinical implementation.

PURPOSE: New insight into the extent of the target volume for the postoperative irradiation of malignant pleural mesothelioma as determined during surgery has indicated that standard conformal radiotherapy (IMRT) is not sufficient for curative treatment. We describe a novel technique for implementing intensity-modulated radiotherapy (IMRT) to deliver higher doses to treat the full extent of these complex target volumes. METHODS AND MATERIALS: After extrapleural pneumonectomy, 7 patients underwent simulation, treatment planning, and treatment with IMRT to the involved hemithorax and adjacent abdomen. The target volumes encompassed the entire operative bed, including the ipsilateral mediastinum, anterior pleural reflection, and ipsilateral pericardium and the insertion of the diaphragm and crura. These were extensively marked during surgery with radiopaque markers to facilitate target delineation. RESULTS: Setup uncertainty and respiratory-dependent motion were found to be small. Coverage of the planning target volume was very good, with the crus of the diaphragm the most difficult volume to irradiate. The radiation doses to normal structures were acceptable. CONCLUSION: IMRT for treatment of malignant mesothelioma after extrapleural pneumonectomy results in more potentially curative doses to large, complex target volumes with acceptable doses to normal tissues.

Humans↗
PubMed2003

Intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) causes symptoms and death mainly due to local progression, even after combined modality treatment. Poor local control after conventional radiotherapy may be due to the low dose of radiation that has been administered or to restriction of the target volume to avoid critical organs. Intensity-modulated radiation therapy (IMRT) has the potential to overcome these geometric/dosimetric constraints. METHODS AND MATERIALS: Seven patients with MPM who had an extrapleural pneumonectomy (EPP) were treated with adjuvant IMRT. The clinical target volume (CTV) included the surgically violated area inside the chest wall with particular attention to the insertion of the diaphragm, pleural reflections, and the deep margin of the thoracotomy incision. Treatment was delivered by intensity-modulated 6-MV photon beams using dynamic multileaf collimation. RESULTS: The CTV ranged from 2667 to 7286 mL. The average CTV covered to 50 Gy was 94% (range, 92% to 98%). Respiratory motion was minimal. The average volume of the boost areas covered by 60 Gy was 92% (range, 82% to 99%). Dose-volume constraints for normal tissue were met in almost all cases. Acute toxicity was mild to moderate. The most severe side effects were anorexia, nausea or vomiting, and dyspnea. Esophagitis was absent or mild. After a minimum of 13 months follow-up care there were no cases of disease recurrence within the ipsilateral hemithorax. CONCLUSION: Treatment of the extensive operative area after an EPP is feasible using IMRT. Input from the radiologist and from the surgeon in the planning process facilitates definition of the high dose volumes. In light of patients' tolerance to post-EPP IMRT, it may be feasible to incorporate systemic therapy, including novel biologic therapies into the treatment regimen.

Aged↗
PubMed2003

Outcomes and patterns of failure in bronchial carcinoid tumors.

PURPOSE: To clarify the natural history, prognosis, and treatment failure patterns for bronchial carcinoid tumors according to their clinical and histopathologic features. METHODS: The charts of 241 patients from our institution with bronchial carcinoid tumors were reviewed. Thirty-four patients had no follow-up, yielding a study population of 206. Of the 206 patients, 62 had atypical carcinoid (AC) and 144 had typical carcinoid (TC) tumors. RESULTS: The 5-, 10-, and 20-year disease-specific survival rates were lower in patients with AC (60.1%, 36.8%, and 28.1%, respectively) than in those with TC (79.0%, 62.9%, and 38.8%, respectively; p = 0.0002). Predictors of poor outcome included more advanced stage (p <0.00001), male gender (p = 0.019), symptoms at presentation (p = 0.013), and age >or=60 years (p = 0.02). Stage I AC was associated with a median disease-free survival of 96 months compared with 222 months for Stage I TC (p = 0.0002) and had an actuarial 22% locoregional failure rate 5 years after surgery compared with 6% for Stage I TC (p = 0.022). The disease-free survival for Stage II and III AC was worse than that for Stage II or III TC, but the difference did not reach statistical significance (p = 0.15). Locoregional failure was also prominent in Stage II and III AC. Second malignancies were common in patients with bronchial carcinoids (56 of 206 patients). CONCLUSION: Stage-for-stage, the outcome is worse for patients with AC than for those with TC. Locoregional failure is common after curative resection, even for early-stage AC. Second cancers are common in patients with carcinoid tumors.

Adult↗
PubMed2003

Tumor oxygenation and acidification are increased in melanoma xenografts after exposure to hyperglycemia and meta-iodo-benzylguanidine.

Tumor oxygen tension and extracellular pH (pH(e)) are physiological parameters that can be manipulated to improve current cancer therapies. Many human tumors consist of cells that are chronically exposed to low pH(e). Exposure of tumor cells in culture to glucose decreases oxygen consumption (oxygen sparing or Crabtree effect), and while this effect is absent in low pH-adapted tumor cells, it can be restored by combining the respiratory inhibitor meta-iodo-benzylguanidine (MIBG) with glucose (Burd et al., Cancer Res. 61, 5630-5635, 2001). The effects of hyperglycemia and MIBG on tumor oxygen tension and on pH(e) were investigated in human melanoma xenografts in SCID mice. An oral gavage of 1 M glucose (2 g/kg) increased the average blood glucose concentration from <140 mg/dl to approximately 400 mg/dl. Although tumor pH(e) decreased from pH 6.7 to pH 6.5 (P < 0.01) after about 60 min, no change in tumor oxygen tension was observed. However, when oral glucose and MIBG (15 mg/kg) were administered together, oxygen tension increased from 2.8 mmHg to approximately 17 mmHg, and tumor pH(e) decreased from pH 6.7 to pH 6.3 (P < 0.01) after about 115 min. In conclusion, administration of glucose together with MIBG increases tumor oxygen tension and also increases the magnitude and duration of acidification. Hyperglycemia plus MIBG has the potential to improve response to radiation therapy as well as to hyperthermia and some chemotherapies.

Animals↗
PubMed2002

Assessment of tissue oxygen tension: comparison of dynamic fluorescence quenching and polarographic electrode technique.

INTRODUCTION AND METHODS: Dynamic fluorescence quenching is a technique that may overcome some of the limitations associated with measurement of tissue partial oxygen tension (PO2). We compared this technique with a polarographic Eppendorf needle electrode method using a saline tonometer in which the PO2 could be controlled. We also tested the fluorescence quenching system in a rodent model of skeletal muscle ischemiahypoxia. RESULTS: Both systems measured PO2 accurately in the tonometer, and there was excellent correlation between them (r(2) = 0.99). The polarographic system exhibited proportional bias that was not evident with the fluorescence method. In vivo, the fluorescence quenching technique provided a readily recordable signal that varied as expected. DISCUSSION: Measurement of tissue PO2 using fluorescence quenching is at least as accurate as measurement using the Eppendorf needle electrode in vitro, and may prove useful in vivo for assessment of tissue oxygenation.

Animals↗