The Effect of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients With Stage III Non-Small Cell Lung Cancer.

PURPOSE: Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at greater risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs affect patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). We aimed to analyze the effect of residing in an FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. METHODS AND MATERIALS: This is a retrospective study of 573 patients with locally advanced NSCLC consecutively treated from January 2000 to January 2020. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence. Cox regression with forward model selection was used for multivariate analysis. RESULTS: Thirty-two percent of patients resided in an FPA (n = 183) and were more likely to self-identify as Black (P < .0001), single (P < .001), <60 years of age (P = .001), and uninsured (P < .0001), with a lower median income (P < .001). Patients in FPAs also had lower mean pre-chemoradiation (CRT) albumin (P = .002), lower pre-CRT body mass index (BMI) (P = .026), and were less likely to receive trimodality therapy (P ≤ .001) compared with patients not living in FPAs. There was no difference in OS or freedom from recurrence between the 2 cohorts. However, in patients with a normal BMI, either pre-CRT (median OS, 18.4 vs 25.0 months; P = .005) or after CRT (15.1 vs 28.1 months, P = .002), residing in an FPA resulted in an OS detriment. CONCLUSIONS: We demonstrated a clear socioeconomic divide in our patient population with stage III NSCLC, where residing in FPAs was associated with less-aggressive therapy and an OS detriment for patients with a normal-weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.

Treatment data and technical process challenges for practical big data efforts in radiation oncology.

The term Big Data has come to encompass a number of concepts and uses within medicine. This paper lays out the relevance and application of large collections of data in the radiation oncology community. We describe the potential importance and uses in clinical practice. The important concepts are then described and how they have been or could be implemented are discussed. Impediments to progress in the collection and use of sufficient quantities of data are also described. Finally, recommendations for how the community can move forward to achieve the potential of big data in radiation oncology are provided.

Overall survival and self-reported fatigue in patients with esophageal cancer.

PURPOSE: A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. METHODS: Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. RESULTS: Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). CONCLUSIONS: A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.

Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE.

BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS: A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS: Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION: This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.

Esophageal self-expandable stent material and mesh grid density are the major determining factors of external beam radiation dose perturbation: results from a phantom model.

BACKGROUND: Self-expandable esophageal stents are increasingly used for palliation or as an adjunct to chemoradiation for esophageal neoplasia. The optimal esophageal stent design and material to minimize dose perturbation with external beam radiation are unknown. We sought to quantify the deviation from intended radiation dose as a function of stent material and mesh density design. METHODS: A laboratory dosimetric film model was used to quantify perturbation of intended radiation dose among 16 different esophageal stents with varying material and stent mesh density design. RESULTS: Radiation dose enhancement due to stent backscatter ranged from 0 % to 7.3 %, collectively representing a standard difference from the intended mean radiation dose of 1.9 (95 % confidence interval [CI] 1.5 - 2.2). This enhancement was negligible for polymer-based stents and approached 0 % for the biodegradable stents. In contrast, all metal alloy stents had significant radiation backscatter; this was largely determined by the density of mesh design and not by the type of alloy used. CONCLUSIONS: Stent characteristics should be considered when selecting the optimal stent for treatment and palliation of malignant esophageal strictures, especially when adjuvant or neo-adjuvant radiotherapy is planned.

Primary pineal tumors: outcome and prognostic factors - a study from the Rare Cancer Network (RCN)

PURPOSE: To better define outcome and prognostic factors in primary pineal tumors. MATERIALS AND METHODS: Thirty-five consecutive patients from seven academic centers of the Rare Cancer Network diagnosed between 1988 and 2006 were included. Median age was 36 years. Surgical resection consisted of biopsy in 12 cases and resection in 21 (2 cases with unknown resection). All patients underwent radiotherapy and 12 patients received also chemotherapy. RESULTS: Histological subtypes were pineoblastoma (PNB) in 21 patients, pineocytoma (PC) in 8 patients and pineocytoma with intermediate differentiation in 6 patients. Six patients with PNB had evidence of spinal seeding. Fifteen patients relapsed (14 PNB and 1 PC) with PNB cases at higher risk (p = 0.031). Median survival time was not reached. Median disease-free survival was 82 months (CI 50 % 28-275). In univariate analysis, age younger than 36 years was an unfavorable prognostic factor (p = 0.003). Patients with metastases at diagnosis had poorer survival (p = 0.048). Late side effects related to radiotherapy were dementia, leukoencephalopathy or memory loss in seven cases, occipital ischemia in one, and grade 3 seizures in two cases. Side effects related to chemotherapy were grade 3-4 leucopenia in five cases, grade 4 thrombocytopenia in three cases, grade 2 anemia in two cases, grade 4 pancytopenia in one case, grade 4 vomiting in one case and renal failure in one case. CONCLUSIONS: Age and dissemination at diagnosis influenced survival in our series. The prevalence of chronic toxicity suggests that new adjuvant strategies are advisable (AU)

SOD2-mediated adaptive responses induced by low-dose ionizing radiation via TNF signaling and amifostine.

Manganese superoxide dismutase (SOD2)-mediated adaptive processes that protect against radiation-induced micronucleus formation can be induced in cells after a 2-Gy exposure by previously exposing them to either low-dose ionizing radiation (10cGy) or WR1065 (40µM), the active thiol form of amifostine. Although both adaptive processes culminate in elevated levels of SOD2 enzymatic activity, the underlying pathways differ in complexity, with the tumor necrosis factor α (TNFα) signaling pathway implicated in the low-dose radiation-induced response, but not in the thiol-induced pathway. The goal of this study was the characterization of the effects of TNFα receptors 1 and 2 (TNFR1, TNFR2) on the adaptive responses induced by low-dose irradiation or thiol exposure using micronucleus formation as an endpoint. BFS-1 wild-type cells with functional TNFR1 and 2 were exposed 24h before a 2-Gy dose of ionizing radiation to either 10cGy or a 40µM dose of WR1065. BFS2C-SH02 cells, defective in TNFR1, and BFS2C-SH22 cells, defective in both TNFR1 and TNFR2 and generated from BFS2C-SH02 cells by transfection with a murine TNFR2-targeting vector and confirmed to be TNFR2 defective by quantitative PCR, were also exposed under similar conditions for comparison. A 10-cGy dose of radiation induced a significant elevation in SOD2 activity in BFS-1 (P<0.001) and BFS2C-SH02 (P=0.005) but not BFS2C-SH22 cells (P=0.433), compared to their respective untreated controls. In contrast, WR1065 significantly induced elevations in SOD2 activity in all three cell lines (P=0.001, P=0.007, P=0.020, respectively). A significant reduction in the frequency of radiation-induced micronuclei was observed in each cell line when exposure to a 2-Gy challenge dose of radiation occurred during the period of maximal elevation in SOD2 activity. However, this adaptive effect was completely inhibited if the cells were transfected 24h before low-dose radiation or thiol exposure with SOD2 siRNA. Under the conditions tested, TNFR1 and 2 inhibition negatively affected the low-dose radiation-induced but not the thiol-induced adaptive responses observed to be mediated by elevations in SOD2 activity.

Treatment results and prognostic factors in primary thyroid lymphoma patients: a rare cancer network study.

BACKGROUND: this study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma. PATIENTS AND METHODS: data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months. RESULTS: sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC. CONCLUSIONS: combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphoma.

Small cell carcinoma of the esophagus: a multicentre Rare Cancer Network study.

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The aims of this retrospective study were to analyze the epidemiology, clinical characteristics, and treatment outcomes of these patients. Between 1994 and 2004, 24 patients with SCCE from several centers were reviewed for data on demographics, presenting symptoms, diagnosis, disease stage, type of treatment, and outcome. SCCE occurs in the sixth decade: median age (interquartile range [IQR]): 65 (59-69) years with a male predominance (63%). The most common complaining symptoms were rapidly progressive dysphagia (79%), weight loss (54%), and retrosternal/epigastric pain (46%). The tumor arises primarily in the middle (52%) or in the lower (35%) third of the esophagus. History of tobacco and alcohol exposure was present in 90% and 70% of case, respectively. Extensive disease was present in 13 cases (54%) at initial diagnosis. The overall median survival (IQR) was 11 (8-20) months for all 24 patients, and the 2-year overall survival was 25.1%. Four patients were alive more than 2 years after treatment. Chemotherapy increased the survival compared with symptomatic management in extensive disease (median survival [IQR]: 9.5 [6-14] vs. 6 [4-7] months, P= 0.05). In limited disease, concurrent chemo-radiotherapy was more effective than non-concurrent treatment (median survival [IQR]: 36 [14-93] vs. 11 [9-15] months, P= 0.04). Two patients were treated by surgery and chemoradiation therapy with a survival of 35 and 66 months. Chemotherapy is the cornerstone of treatment of SCCE in all stage. For limited disease SCCE, concurrent chemo-radiotherapy is the primary choice compared with sequential approach. The role of surgery was not assessable in our study.

[Prostate cancer: what role for curative radiotherapy in elderly?]. / Cancers de prostate: quelle place pour la radiothérapie à visée curative chez les patients âgés?

PURPOSE: Discuss the place of radiotherapy given in a curative intent in elderly patients with localised prostate cancer according to complications, local control, survival observed in a specific and a review of the literature. PATIENTS AND METHODS: The cohort consisted of 65 males aged 80 or more with localised prostate cancer who choose radiotherapy as a curative modality. Twelve radiotherapy centres affiliated to the Rare Cancer Network participated to the study. The retrospective analysis was carried out on immediate and late side-effects, biological free of relapse survival and global survival. Multivariate analysis took into account the comorbidities, the initial prostatic specific antigen (PSA) value, the Gleason score and the therapeutic modalities. RESULTS: From January 1990 to December 2000, 65 patients were included into the cohort. Mean age was 81 years. The specific series consisted of 10 T1, 40 T2 and 15 T3 N0M0. Median follow up was 65 months. Immediate and late complications were comparable to those described in younger patients who received a similar irradiation. There were no negative impact of the treatment on disease free survival and global survival. Recent literature did suggest analogous results. CONCLUSIONS: Radiation therapy with a curative intent should not be systematically withheld in elderly patients with localised prostate cancer.

Impact of endoscopic ultrasonography and physician specialty on the management of patients with esophagus cancer.

While endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are the most accurate techniques for locoregional staging of esophageal cancer, little evidence exists that these innovations impact on clinical care. The objective on this study was to determine the frequency with which EUS and EUS-FNA alter the management of patients with localized esophageal cancer, and assess practice variation among specialists at a tertiary care center. Three gastroenterologists, three medical oncologists, three radiation oncologists and four thoracic surgeons were asked to independently report their management recommendations as the anonymized staging information of 50 prospectively enrolled patients from another study were sequentially disclosed on-line. Compared to initial management recommendations, that were based upon history, physical examination, upper endoscopy and CT scan results, EUS prompted a change in management 24% (95% CI: 12-36%) of the time; usually to a more resource-intensive approach (71%), for example from recommending palliation to recommending neoadjuvant chemoradiation therapy. EUS-FNA plus cytology results altered management an additional 8% (95% CI: 6-15%) of the time. Agreement between specialists ranged from fair (intraclass correlation [ICC=0.32) to substantial (ICC=0.65); improving with additional information. Among specialists, agreement was greatest for patients with stage I disease. EUS and EUS-FNA changed patient management the most for patients with stages IIA, IIB or III disease. EUS, with or without FNA, significantly impacts the management of patients with localized esophageal cancer. With respect to the optimal treatment for each patient, agreement among physicians incrementally increases with endoscopic ultrasound results. Specialty training appears to influence therapeutic decision-making behavior.

Non-traumatic vertebral fractures in patients with locally advanced esophageal cancer: a previously unreported, unrecognized problem.

Recent studies suggest cancer therapy may compromise bone integrity. What is the rate of vertebral fractures among patients who have received trimodality therapy (radiation, chemotherapy, and surgery) for locally advanced esophageal cancer? This single-institution, retrospective study attempted to answer this question, focusing on 337 patients who had received trimodality therapy for locally advanced esophageal cancer between 1996 and 2005. Reports of serial radiographs were reviewed to identify vertebral fractures. Duration of follow-up was gathered for all esophageal cancer patients with the intention of calculating fracture incidence rates. Fracture-related symptoms, types of intervention and fracture recurrence were also gleaned from the clinical records. First-time fractures were identified in 47 patients, and 45 of these were new since the cancer diagnosis. Thus, the first-time fracture incidence rate from the time of cancer diagnosis was 12 fractures per 100 patient years. The median time from cancer diagnosis to fracture was 9 months. Fifteen (33%) patients were symptomatic. Acknowledging that a retrospective study can inadvertently result in information omission, we report that pain medications were started in only seven patients (16%), and osteoporosis medication in only six (13%). Two patients were hospitalized, and two underwent vertebroplasty. The median survival after fracture diagnosis was 36 months. This report describes a seemingly high fracture incidence rate that requires confirmation. If confirmed, future studies should focus on identifying risk factors and optimal strategies for the prevention and treatment of vertebral fractures in patients with esophageal cancer.

Curing patients with locally advanced esophageal cancer: an update on multimodality therapy.

Combining different treatment modalities--such as surgery, radiation, and chemotherapy--is often utilized to treat patients with locally advanced esophageal cancer. However, it remains controversial how best to combine these modalities to provide patients with the greatest chance of cure. This review discusses recent studies in this field and outlines promising versus less promising therapeutic strategies.

Intraoperative radiotherapy for treatment of locally advanced and recurrent esophageal and gastric adenocarcinomas.

Intraoperative radiotherapy (IORT) allows delivery of radiotherapy doses in excess of those typically deliverable with conventional external beam radiotherapy. IORT has potential utility in clinical situations, such as treatment of esophageal and gastric malignancies, in which the radiation tolerance of normal organs limits the dose that can be given with conventional radiotherapy techniques. We reviewed the records of 50 patients who received IORT for locally advanced primary or recurrent gastric or esophageal adenocarcinomas deemed unresectable for cure. IORT was given as a single fraction of electron beam radiotherapy (10-25 Gy) after maximal tumor resection: R0 in 42%, R1 in 46%, and R2 in 12%. Forty-eight patients also received external beam radiotherapy (8-55 Gy), 46 received radiosensitizing chemotherapy, and nine received systemic chemotherapy after radiotherapy. Outcomes were estimated with Kaplan-Meier analysis. Median survival was 1.6 years. Overall survival at 1, 2, and 3 years was 70%, 40%, and 27%. Of 42 patients who died, 37 died from cancer progression and three from multifactorial treatment toxicity. Median survival for patients with recurrent disease versus primary disease was 3.0 years versus 1.3 years (P < 0.05), with a delay of metastatic failure in patients with recurrent tumors (P = 0.06). At 3 years, distant metastatic failure was 79%, local failure was 10%, and regional failure was 15%. IORT for locally advanced primary or recurrent gastric malignancies effectively decreases the risk of local failure. For patients with isolated local recurrences, IORT may be effective salvage therapy. However, more effective systemic therapy is needed as a component of treatment.

Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierarchical method.

BACKGROUND: We evaluate the performance of ovulation detection methods and present new approaches, including evaluation of methods for precision, combining multiple markers into a hierarchical system and using ovulation markers in intermittent sampling designs. METHODS: With serum LH peak day as the 'gold standard' of ovulation, we estimated accuracy and precision of ovulation day algorithms using 30 ovulatory menstrual cycles with daily urinary and serum hormones and transvaginal ultrasound. Sensitivity and specificity for estimating the presence of ovulation were tested using visually assessed ovulatory (30) and anovulatory (22) cycles. RESULTS: Sensitivity and specificity ranged from 70 to 100% for estimating presence of ovulation with twice-per-cycle, weekly, twice weekly, every-other-day and daily specimens. A combined hierarchical method estimated ovulation day using daily specimens within +/-2 days of the gold standard in 93% of cases. Accuracy of estimating ovulation day within +/-2 days using intermittent sampling ranged from 40% (weekly sampling) to 97% (every-other-day). CONCLUSIONS: A combined hierarchical algorithm using precise and accurate markers allows maximal use of available data for efficient and objective identification of ovulation using daily specimens. In intermittent sampling designs, the presence and the timing of ovulation can be estimated with good sensitivity, specificity and accuracy.

A Canadian high-energy neutron spectrometry system for measurements in space.

Bubble Technology Industries Inc. (BTI), with the support of the Canadian Space Agency, has finished the construction of the Canadian High-Energy Neutron Spectrometry System (CHENSS). This spectrometer is intended to measure the high energy neutron spectrum (approximately 1-100 MeV) encountered in spacecraft in low earth orbit. CHENSS is designed to fly aboard a US space shuttle and its scientific results should facilitate the prediction of neutron dose to astronauts in space from readings of different types of radiation dosimeters that are being used in various missions.

Routine screening mammography: how important is the radiation-risk side of the benefit-risk equation?

The potential radiation hazards associated with routine screening mammography, in terms of breast cancer induction, are discussed in the context of the potential benefits. The very low energy X-rays used in screening mammography (26-30 kVp) are expected to be more hazardous, per unit dose, than high-energy X- or gamma-rays, such as those to which A-bomb survivors (from which radiation risk estimates are derived) were exposed. Based on in vitro studies using oncogenic transformation and chromosome aberration end-points, as well as theoretical estimates, it seems likely that low doses of low-energy X-rays produce an increased risk per unit dose (compared with high energy photons) of about a factor of 2. Because of the low doses involved in screening mammography, the benefit-risk ratio for older women would still be expected to be large, though for younger women the increase in the estimated radiation risk suggests a somewhat later age than currently recommended--by about 5-10 years--at which to commence routine breast screening.

A novel long chain polyunsaturated fatty acid, beta-Oxa 21:3n-3, inhibits T lymphocyte proliferation, cytokine production, delayed-type hypersensitivity, and carrageenan-induced paw reaction and selectively targets intracellular signals.

A novel polyunsaturated fatty acid (PUFA), beta-oxa 21:3n-3, containing an oxygen atom in the beta position, was chemically synthesized, and found to have more selective biological activity than the n-3 PUFA, docosahexaenoic acid (22:6n-3) on cells of the immune system. Although beta-oxa 21:3n-3 was very poor compared with 22:6n-3 at stimulating oxygen radical production in neutrophils, it was more effective at inhibiting human T lymphocyte proliferation (IC(50) of 1.9 vs 5.2 microM, respectively). beta-Oxa 21:3n-3 also inhibited the production of TNF-beta, IFN-gamma, and IL-2 by purified human T lymphocytes stimulated with PHA plus PMA, anti-CD3 plus anti-CD28 mAbs, or PMA plus A23187. Metabolism of beta-oxa 21:3n-3 via the cyclooxygenase and lipoxygenase pathways was not required for its inhibitory effects. Consistent with its ability to suppress T lymphocyte function, beta-oxa 21:3n-3 significantly inhibited the delayed-type hypersensitivity response and carrageenan-induced paw edema in mice. In T lymphocytes, beta-oxa 21:3n-3 inhibited the agonist-stimulated translocation of protein kinase C-betaI and -epsilon, but not -alpha, -betaII, or -theta to a particulate fraction, and also inhibited the activation of the extracellular signal-regulated protein kinase, but not c-Jun NH(2)-terminal kinase and p38. In contrast, 22:6n-3 had no effects on these protein kinase C isozymes. The increase in antiinflammatory activity and loss of unwanted bioaction through the generation of a novel synthetic 22:6n-3 analogue provides evidence for a novel strategy in the development of anti-inflammatory agents by chemically engineering PUFA.

Measurement of chemopreventive efficacy in skin biopsies.

OBJECTIVE: To explore methods suitable for quantitative assessment of the efficacy of chemopreventive intervention. STUDY DESIGN: High-resolution imagery of nuclei from the suprabasal and basal cell layers of sun-damaged skin were recorded. There were 10 cases. A shave biopsy was taken from an area of clearly evident solar keratosis before and after treatment with 2-difluoromethyl-dlornithine (DFMO) and from the colateral forearm, treated with a placebo. A number of karyometric variables were computed and combined to derive marker features that provided a numeric measure of the degree of nuclear deviation from normal. RESULTS: DFMO treatment was effective overall in reducing the degree of nuclear abnormality seen in the biopsies; in 8 of the 10 cases there was a significant improvement. The placebo-treated arm did not show a statistically different abnormality from the untreated arm. CONCLUSION: Karyometric analysis can provide numeric measures that allow documentation of statistically significant regression of actinic keratotic lesions following treatment with DFMO.

Long-term efficacy of intracoronary irradiation in inhibiting in-stent restenosis.

BACKGROUND: Intracoronary irradiation is a promising modality for inhibition of in-stent restenosis. Results of randomized clinical trials at 6 months after gamma ray irradiation are highly encouraging. The first results at 3 years after irradiation, while still showing benefit, have shown significant late loss. The probable mechanism of the radiation is to inactivate (prevent from dividing) most cells that otherwise could proliferate to produce neointimal formation. We measured the proportion of cells that survive with their clonogenic potential intact after the doses and dose rates used in the randomized trials, and we then modeled the subsequent repopulation of the surviving cells that might cause late restenosis. METHODS AND RESULTS: Human aortic smooth muscle cells were irradiated with gamma rays, including the doses and dose rates used in current trials, and clonogenic surviving fractions were measured. The subsequent repopulation of the surviving cells was modeled with the assumption that the repopulation kinetics were similar to those in unirradiated cells. The radiation is expected to delay the time to restenosis by factors of approximately 6 to 8, depending on the dose, shifting the delay from a median of 6 months (for no irradiation) to median values from 36 months (for a nominal 13 Gy) to 43 months (for a nominal 15 Gy). CONCLUSIONS: These results and predictions are quantitatively consistent with clinical results and suggest that clonogenic inactivation (prevention of cellular division) is the dominant mechanism of radiation action in the delay of restenosis. Intracoronary radiotherapy is a very promising modality for significantly delaying, although probably not preventing, in-stent restenosis.