Study on the value of the prenatal-postnatal integrated management model in the screening, diagnosis, and treatment of fetal heart malformations.

OBJECTIVE: With the development and widespread use of fetal ultrasound and magnetic resonance technology in recent years, approximately 75% of fetuses are diagnosed prenatally with congenital structural malformations, a serious birth defect that endangers the life and health of the newborn. In this study, we aimed to study and analyze the value of the prenatal-postnatal integrated management model in the screening, diagnosis and treatment of fetal heart malformations. PATIENTS AND METHODS: All pregnant women who were to undergo delivery in our hospital between January 2018 and December 2021 were recruited as the first subjects in this study, and after excluding those who refused to participate in the study, a total of 3,238 cases were finally included as subjects of this study. All pregnant women were screened for fetal heart malformations using the prenatal-postnatal integrated management model. Maternal files were established for all cases of heart malformations, grading the fetuses according to their heart disease grade, observing and recording their deliveries, treatment results and follow-ups. RESULTS: After screening for heart malformations using the prenatal-postnatal integrated management model, 33 cases of heart malformations were identified, including 5 cases of Grade I (all delivered), 6 cases of Grade II (all delivered), 10 cases of Grade III (1 induced), and 12 cases of Grade IV (1 induced); 2 cases of ventricular septal defect healed spontaneously after delivery, and 18 infants were treated accordingly. The results of the later follow-up showed that 10 children had normalized their heart structure, 7 cases had slight alterations in the heart valves, and 1 case died. CONCLUSIONS: The prenatal-postnatal integrated management model is a multidisciplinary cooperation model with certain clinical value in the screening, diagnosis and treatment of fetal heart malformations, which is beneficial to comprehensively improve the ability of hospital physicians in the grading management of heart malformations, detecting fetal heart malformations early and predicting fetal changes after birth. It further reduces the incidence of serious birth defects, conforms to the development trend of the diagnosis and treatment of congenital heart diseases, enables to reduce child mortality with timely treatment, effectively improves the surgical prognosis of critical and complex congenital heart diseases, with a promising application prospect.

[Analysis of etiological characteristics and establishment of prediction model of postoperative infections in patients undergoing oral squamous cell carcinoma surgery with free flap reconstruction].

OBJECTIVE: To investigate the characteristics of pathogen infection and to establish a prediction model of infections in oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction. METHODS: The retrospective cohort study consisted of 1 596 patients undergoing tumor resection and free flap reconstruction for oral squamous cell carcinoma from January 2018 to December 2020. According to the postoperative infection, the patients were divided into the infected group (n=154) and non-infected group (n=1 442). The characteristics of pathogens were analyzed in the infected patients. The primary outcome variable was postoperative infection, and Logistic regression was used to determine risk factors of the infection. The prediction model was established and the discriminatory accuracy of the model was evaluated using receiver operating characteristic (ROC) curve. RESULTS: Totally 154 cases were infected in the 1 596 cases undergoing surgery with free flap reconstruction, and the infection rate was 9.65%. The most frequent sites of infection were the surgical wound and respiratory tract. A total of 268 pathogens were isolated and cultured, including 240 strains of Gram-negative bacteria, accounting for 89.55%, mainly Pseudomonas aeruginosa and Klebsiella pneumoniae; 23 strains of Gram-positive bacteria, accounting for 8.58%, mainly Enterococcus faecalis and Staphylococcus aureus; and 5 strains of fungi, accounting for 1.87%. The isolated Pseudomonas aeruginosa had high resistant rate to imipenem and meropenem, and was sensitive to antibiotics, such as ciprofloxacin. The isolated Staphylococcus aureus had high resistant rate to erythromycin and clindamycin, and was sensitive to vancomycin. According to the multivariate Logistic analysis, four independent variables were significantly associated with an increased risk of postoperative infection (P < 0.05): clinical N category≥1, the American Society of Anesthesiologists (ASA) grade ≥2, tracheotomy and length of hospital stay >13 d. The prediction model was established based on these factors and the expression of the risk prediction model was as follows: predicted probability value P=1/(1+e-a), a=-0.803+0.674×(clinical N category ≥1)+0.518×(the ASA grade ≥2)+0.918×(tracheotomy)+1.581×(length of hospital stay >13 d), Hosmer-Lemeshow χ2=10.647, P=0.223, the degree of fitting of the model was good. The area under the ROC curve was 0.818 and 95%CI of the model for predicting infection was 0.789-0.846. CONCLUSION: Oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction are prone to have a high incidence of postoperative infection and Gram-negative bacteria are the main pathogens causing an infection. The established prediction model is of good predictive effect. Rational antimicrobial use coupled with awareness of infection control measures is paramount to reduce the incidence of postoperative infection in the oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction.

Nonlinear dynamics of laser-generated ion-plasma gratings: A unified description.

Laser-generated plasma gratings are dynamic optical elements for the manipulation of coherent light at high intensities, beyond the damage threshold of solid-state-based materials. Their formation, evolution, and final collapse require a detailed understanding. In this paper, we present a model to explain the nonlinear dynamics of high-amplitude plasma gratings in the spatially periodic ponderomotive potential generated by two identical counterpropagating lasers. Both fluid and kinetic aspects of the grating dynamics are analyzed. It is shown that the adiabatic electron compression plays a crucial role as the electron pressure may reflect the ions from the grating and induce the grating to break in an X-type manner. A single parameter is found to determine the behavior of the grating and distinguish three fundamentally different regimes for the ion dynamics: completely reflecting, partially reflecting or passing, and crossing. Criteria for saturation and lifetime of the grating as well as the effect of finite ion temperature are presented.

Expression of hypoxia-inducible factor-1α during ovarian follicular growth and development in Sprague-Dawley rats.

Hypoxia-inducible factor-1α (HIF-1α) has been identified as a transcription factor that is involved in diverse physiological and pathological processes in the ovary. In this study, we examined whether HIF-1α is expressed in a cell- and stage-specific manner during follicular growth and development in the mammalian ovaries. Using immunohistochemistry and Western blot analysis, HIF-1α expression was observed in granulosa cells specifically and was significantly increased during the follicular growth and development of postnatal rats. Furthermore, pregnant mare serum gonadotropin also induced HIF-1α expression in granulosa cells and ovaries during the follicular development of immature rats primed with gonadotropin. Moreover, we also examined proliferation cell nuclear antigen, a cell proliferation marker, during follicular growth and development and found that its expression pattern was similar to that of HIF-1α protein. Granulosa cell culture experiments revealed that proliferation cell nuclear antigen expression may be regulated by HIF-1α. These results indicated that HIF-1α plays an important role in the follicular growth and development of these 2 rat models. The HIF-1α-mediated signaling pathway may be an important mechanism regulating follicular growth and development in mammalian ovaries in vivo.

A novel marine bacterium algicidal to the toxic dinoflagellate Alexandrium tamarense.

AIMS: This work is aiming at investigating algicidal characterization of a bacterium isolate DHQ25 against harmful alga Alexandrium tamarense. METHODS AND RESULTS: 16S rDNA sequence analysis showed that the most probable affiliation of DHQ25 belongs to the γ-proteobacteria subclass and the genus Vibrio. Bacterial isolate DHQ25 showed algicidal activity through an indirect attack. Xenic culture of A. tamarense was susceptible to the culture filtrate of DHQ25 by algicidal activity assay. Algicidal process demonstrated that the alga cell lysed and cellular substances released under the visual field of microscope. DHQ25 was a challenge controller of A. tamarense by the above characterizations of algicidal activity assay and algicidal process. CONCLUSION: Interactions between bacteria and harmful algal bloom (HAB) species proved to be an important factor regulating the population of these algae. SIGNIFICANCE AND IMPACT OF STUDY: This is the first report of a Vibrio sp. bacterium algicidal to the toxic dinoflagellate A. tamarense. The findings increase our knowledge of the role of bacteria in algal-bacterial interaction.

Microbial modulation in the biomass and toxin production of a red-tide causing alga.

The effect of S10, a strain of marine bacteria isolated from sediment in the Western Xiamen Sea, on the growth and paralytic shellfish poison (PSP) production in the alga Alexandrium tamarense (A. tamarense) was studied under controlled experimental conditions. The results of these experiments have shown that the growth of A. tamarense is obviously inhibited by S10 at high concentrations, however no evident effect on its growth was observed at low concentrations. Its PSP production was also inhibited by S10 at different concentrations, especially at low concentrations. The toxicity of this strain of A. tamarense is about (0.95-12.14) x 10(-6) MU/cell, a peak toxicity value of 12.14 x 10(-6) MU/cell appeared on the 14th day, after which levels decreased gradually. The alga grew well in conditions of pH 6-8 and salinities of 20-34 per thousand. The toxicity of the alga varied markedly at different pH and salinity levels. Toxicity decreased as pH increased, while it increased with salinity and reached a peak value at a salinity of 30 per thousand, after which it declined gradually. S10 at a concentration of 1.02 x 10(9) cells/ml inhibited growth and the PSP production of A. tamarense at different pH and salinity levels. S10 had the strongest inhibitory function on the growth of A. tamarense under conditions of pH 7 and a salinity of 34 per thousand. The best inhibitory effect on PSP production by A. tamarense was at pH 7, this inhibitory effect on PSP production did not relate to salinity. Interactions between marine bacteria and A. tamarense were also investigated using the flow cytometer technique (FCM) as well as direct microscope counting. S10 was identified as being a member of the genus Bacillus, the difference in 16S rDNA between S10 and Bacillus halmapalus was only 2%. The mechanism involved in the inhibition of growth and PSP production of A. tamarense by this strain of marine bacteria, and the prospect of using it and other marine bacteria in the bio-control of red-tides was discussed.

Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group.

BACKGROUND: Immune responses mediated by IgE are important in the pathogenesis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE and blocks its interaction with mast cells and basophils. We studied the efficacy of rhuMab-E25 as a treatment for moderate-to-severe allergic asthma. METHODS: After a 4-week run-in period, we randomly assigned 317 subjects (age range, 11 to 50 years) who required inhaled or oral corticosteroids (or both) to receive either placebo or one of two regimens of rhuMAB-E25: high-dose rhuMAb-E25 (5.8 microg per kilogram of body weight per nanogram of IgE per milliliter or low-dose rhuMAb-E25 (2.5 microg per kilogram per nanogram of IgE per milliliter) intravenously on days 0 (half a dose), 4 (half a dose), and 7 (full dose) and then once every 2 weeks thereafter for 20 weeks. For the first 12 weeks of the study, the subjects continued the regimen of corticosteroids they had received before enrollment. During the following eight weeks, the doses of corticosteroids were tapered in an effort to discontinue this therapy. The primary outcome measure was an improvement in the asthma symptom score at 12 weeks, according to a 7-point scale, in which a score of 1 indicated no symptoms and a score of 7 the most severe symptoms. RESULTS: A total of 106 subjects were assigned to receive a high dose of rhuMAb-E25, 106 were assigned to receive a low dose, and 105 were assigned to receive placebo. At base line, the mean asthma symptom score was 4.0. After 12 weeks of therapy, the mean (+/-SE) scores were 2.8+/-0.1 in the high-dose group (P=0.008) and 2.8+/-0.1 in the low-dose group (P=0.005), as compared with 3.8+/-0.1 in the placebo group. At 20 weeks, the mean scores were 2.7+/-0.1 in both the high-dose group (P=0.048) and the low-dose group (P=0.14), as compared with 2.9+/-0.1 in the placebo group. More subjects in the two rhuMAb-E25 groups were able to decrease or discontinue their use of corticosteroids than in the placebo group, but only some of the differences were significant. After 20 weeks, serum free IgE concentrations decreased by a mean of more than 95 percent in both rhuMAb-E25 groups. The therapy was well tolerated. After 20 weeks, none of the subjects had antibodies against rhuMAb-E25. CONCLUSIONS: A recombinant humanized monoclonal antibody directed against IgE has potential as a treatment for subjects with moderate or severe allergic asthma.

Effect of aerosolized anti-IgE (E25) on airway responses to inhaled allergen in asthmatic subjects.

Intravenous administration of a humanized monoclonal antibody of IgE (E25) attenuates the early and late phase response to inhaled allergen in allergic asthmatic subjects. To test whether direct delivery of E25 to the airway might have the same effect, we conducted a randomized, double-blind, three group study in 33 subjects with mild allergic asthma (20 to 46 yr of age, 21 men, FEV(1) > 70% predicted). The airway responses to aerosolized allergen were determined at baseline, after 2 and 8 wk of once daily treatment with aerosolized placebo (n = 11), aerosolized E25 1 mg (n = 12), or aerosolized E25 10 mg (n = 10), and after 4 wk of treatment withdrawal. We found that E25 was detectable in the serum during aerosol treatment, although serum IgE did not change significantly in any of the three groups during treatment. In addition, both doses of E25 were no more effective than placebo in attenuating the early phase responses to allergen at both times during treatment. Although aerosolized E25 was generally well tolerated, one subject receiving aerosolized E25 10 mg daily was found to have serum IgG and IgA antibodies to E25. We conclude that aerosol administration of an anti-IgE monoclonal antibody does not inhibit the airway responses to inhaled allergen in allergic asthmatic subjects. We speculate that the observed lack of efficacy may be due to the inability of aerosol route of delivery to result in high enough concentrations of E25 in the tissue compartments surrounding IgE effector cells to neutralize IgE arising from local airway and pulmonary sources and IgE arising from the vascular space. Additionally, the aerosol route of delivery of monoclonal antibodies may be more immunogenic than the parenteral route.

Analysis of repeated markers used to predict progression of cancer.

We consider methods for evaluating repeated markers to be used as a substitute for a clinical examination or to predict an outcome, in our case progression of breast cancer. We propose a definition of specificity and sensitivity for this setting and describe non-parametric estimators for these parameters. We then derive the theory required to obtain confidence intervals for the specificity and sensitivity of a marker and to define an asymptotically normal statistic for comparing the sensitivities of two markers at a fixed specificity. The theory allows for correlations introduced by the fact that markers may be obtained from the same patient at multiple visits and that both markers being compared may be obtained from the same patient. The work allows for an approach that complements the frequently used time dependent Cox model, which we believe, will facilitate clinical interpretation of marker data.

Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis.

BACKGROUND: Increased serum levels of antigen-specific IgE are often associated with allergic respiratory disorders. RhuMAb-E25, a recombinant humanized monoclonal antibody, decreases free serum IgE by forming biologically inactive immune complexes with free IgE. OBJECTIVE: We hypothesized that rhuMAb-E25 would decrease total serum IgE and reduce symptoms. METHODS: Two hundred forty subjects were enrolled into five groups to determine the safety, tolerance, and efficacy of repeated administration of rhuMAb-E25 in adults with ragweed-induced allergic rhinitis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE. One hundred eighty-one subjects received an initial intravenous loading dose (day 0, 1 month before ragweed season), followed by administration of rhuMAb-E25 (in mg/kg body weight) of 0.15 mg/kg subcutaneously, 0.15 mg/kg intravenously, or 0.5 mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo group and an intravenous placebo group were included. The total evaluation time included the 84-day treatment period, followed by a 42-day observation period. RESULTS: Adverse events were mild, and no differences were observed in the rates between the three active and two placebo treatment groups. Ragweed-specific IgE levels correlated with symptom scores. RhuMAb-E25 decreased serum free IgE levels in a dose- and baseline IgE-dependent fashion. However, only 11 subjects had IgE levels that were suppressed to undetectable levels (< or = 24 ng/ml), a sample too small to demonstrate significant differences and clinical efficacy. Thus the case for efficacy was not proven. Nonetheless, the study confirms that it is safe to repeatedly administer rhuMAb-E25 over a period of months. CONCLUSIONS: Because rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because symptom scores correlated with antigen-specific IgE levels, the results suggest that if given in adequate doses, rhuMAb-E25 should be an effective therapy for allergic diseases.

The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects.

A humanized murine monoclonal antibody directed to the Fc epsilonR1-binding domain of human IgE (rhuMAb-E25) has been shown to inhibit the binding of IgE to mast cells without provoking mast cell activation. To examine the effects of neutralizing IgE on allergic airway responses, we assessed the effects of 9 wk of treatment with rhuMAb-E25 in a parallel group, randomized, double-blind, placebo-controlled study of 19 allergic asthmatic subjects. We found that treatment with rhuMAb-E25 reduced serum IgE, increased the dose of allergen needed to provoke an early asthmatic response, reduced the mean maximal fall in FEV1 during the early response (30 +/- 10% at baseline to 18.8 +/- 8%, versus 33 +/- 8% at baseline to 34 +/- 4% after placebo; p = 0.01), and reduced the mean maximal fall in FEV1 during the late response (24 +/- 20% at baseline to 9 +/- 10% versus 20 +/- 17% at baseline to 18 +/- 17% after placebo; p = 0.047). We conclude that an anti-IgE monoclonal antibody, which inhibits binding of IgE to its receptor, suppresses the early- and late-phase responses to inhaled allergen in allergic asthmatic subjects. Targeting IgE with rhuMAb-E25 might be a useful treatment for allergic asthma.

Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response.

Inhaled allergens, acting through IgE-dependent mechanisms, are important triggers of asthma symptoms and inducers of airway hyperresponsiveness and airway inflammation. The effect of anti-IgE recombinant humanized monoclonal antibody-E25 (rhuMAb-E25) on the provocation concentration of allergen causing a 15% fall in FEV1 (allergen PC15) during the allergen-induced early asthmatic response (EAR) was assessed in a multicenter, randomized, double-blind, parallel group study. Ten of 11 allergic asthmatic subjects randomized to receive intravenous rhuMAb-E25, 2 mg/kg on study day 0 and 1 mg/kg on Days 7, 14, 28, 42, 56, and 70 completed the study; nine received intravenous placebo. The allergen PC15 was measured on Days -1, 27, 55, and 77 and methacholine PC20 on Days -2, 42, and 76. rhuMAb-25 was well tolerated and only one patient (active group) was withdrawn because of a generalized urticarial rash after the first dose. Compared with baseline values (Day -1), the median allergen PC15 on Days 27, 55, and 77 were increased by 2.3, 2.2, and 2.7 doubling doses (delta log PC15/0.3) respectively with rhuMAb-E25 and -0.3, +0.1, and -0.8 doubling doses with placebo (p < or = 0.002). Methacholine PC20 improved slightly after rhuMAb-E25, this change becoming statistically significant on Day 76 (p < 0.05); no change was observed in the placebo group. Mean serum-free IgE fell by 89% after rhuMAb-E25 while there was no significant change after placebo. The inhibitory effects of rhuMAb-E25 on allergen-induced EAR suggest that it may be an effective, novel antiallergic treatment for asthma.

Etoposide-cisplatin and thoracic radiation therapy salvage of incomplete responders to a noncisplatin induction regimen for limited and extensive small-cell carcinoma of the lung.

Our purpose was to determine the ability of an etoposide-cisplatin (EP )-based regimen to salvage patients with limited and extensive small-cell lung cancer who are incomplete responders to cyclophosphamide-Adriamycin-vincristine-etoposide (CAVE) chemotherapy, and to determine the ability of thoracic radiation therapy (TRT) to salvage CAVE and EP incomplete responders. Fifty-eight patients with small-cell lung cancer (33, limited disease; 25, extensive disease) were entered on this Phase II study between November 1984 and December 1987. Patients received three cycles of CAVE chemotherapy, followed by two cycles of CEPi (cyclophosphamide-etoposide-cisplatin (infusional) and two cycles of CE (cyclophosphamide-etoposide) in conjunction with TRT and prophylactic cranial irradiation (PCI). The overall response rate to CAVE was 62% [5% complete response (CR), 57% partial response (PR) + regression (REGR)]. Of the patients who failed to achieve a CR with CAVE, 81% responded to CEPi (44% CR, 36% PR). Of the patients who did not achieve a CR with either CAVE or CEPi, 89% responded to TRT (65% CR, 24% PR + REGR). For the 33 patients with limited disease, the median survival time and 2-year survival rate were 16.1 months and 24%, respectively. The corresponding figures for the 25 patients with extensive disease were 9.8 months and 4%, respectively. Eleven of these 25 patients were "downstaged" to "limited disease" with CAVE + CEPi and then received TRT + PCI + CE. Their median survival time and 2-year survival rate were 12.6 months and 9%, respectively. The EP-based regimen CEPi and TRT were able to convert 44 to 65% of patients to a complete response who had failed to do so with non-EP induction chemotherapy. This study supports the use of an EP regimen with TRT as initial therapy for newly diagnosed small-cell lung cancer.

Infusion cisplatin chemotherapy and hyperfractionated thoracic radiotherapy for small-cell lung cancer.

Sixty patients, 29 with limited disease and 31 with extensive disease, received an infusion cisplatin-based chemotherapy regimen and, where applicable, subsequent hyperfractionated thoracic radiation therapy (HTRT). Of the patients with limited disease, the response rate was 100% (76% complete response); median survival 26.5 months; 1- and 2-year survival 90 and 55%, respectively. Of those with extensive disease,96% responded (36% complete response) with median survival 12.0 months and 1- and 2-year survival 48 and 29%, respectively. Thirty-five percent of extensive disease patients were downstaged to a "limited" status. with a median survival of 20.3 months. Grade IV leukopenia and thrombocytopenia were seen in 25 and 7% of patients, respectively, with one patient dying of radiation pneumonitis. Within the constraints of the study, infusion cisplatin-based chemotherapy and HTRT appear to be a safe and effective program for the treatment of small-cell lung cancer.

Prophylactic cranial irradiation in limited-stage small cell lung cancer.

BACKGROUND: The role of prophylactic cranial irradiation (PCI) for patients with limited-stage small cell lung cancer (LSSCLC) remains a controversial issue. This study evaluated PCI in patients with LSSCLC who achieved a complete response to initial chemotherapy. METHODS: A retrospective case study of all nonprotocol patients with LSSCLC examined at our institution from 1982 to 1990 was performed. Of the 67 nonprotocol patients who were treated with combination chemotherapy (cyclophosphamide-based) and thoracic radiotherapy during those years, 43 achieved a complete response. Twenty-four patients received prophylactic cranial irradiation (PCI+) (25-36 Gy in 10-16 fractions), and 19 did not (PCI-) at the physician's or patient's discretion. RESULTS: The distribution of prognostic factors between the PCI+ and PCI- groups was well balanced. Of the PCI+ patients, the 2-year actuarial freedom from relapse in the central nervous system was 93% versus 47% for the PCI- patients (log rank analysis, P = 0.001). An initial central nervous system relapse developed in 2 of the 24 PCI+ patients as the only site of failure versus 7 of 19 PCI- patients (P = 0.003). The 2-year actuarial overall survival was 50% for the PCI+ patients versus 21% for the PCI- patients (P = 0.01). The addition of prophylactic cranial irradiation was the only significant factor contributing to an improvement in time to central nervous system relapse and survival for the PCI+ patients. There were five patients alive at the time of this report, and all received prophylactic cranial irradiation. None had cognitive or neurologic impairment. CONCLUSIONS: Prophylactic cranial irradiation may contribute to improved survival in patients with LSSCLC who achieve a complete response after chemotherapy and thoracic radiation therapy.

Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer.

PURPOSE: Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population. METHODS AND MATERIALS: Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease. RESULTS: Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively. CONCLUSION: Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting.

Non-parametric estimation for the difference or ratio of median failure times for paired observations.

We propose a non-parametric method to calculate a confidence interval for the difference or ratio of two median failure times for paired observations with censoring. The new method is simple to calculate, does not involve non-parametric density estimates, and is valid asymptotically even when the two underlying distribution functions differ in shape. The method also allows missing observations. We report numerical studies to examine the performance of the new method for practical sample sizes.

Prognostic value of c-erbB2 overexpression in axillary lymph node positive breast cancer. Results from a randomized adjuvant treatment protocol.

BACKGROUND: This study was designed to evaluate the prognostic importance of c-erbB2 overexpression in a standardized cohort of patients with axillary lymph node positive breast cancer. METHODS: Paraffin embedded primary breast cancers from 354 patients with axillary lymph node positive breast cancer, treated on a North Central Cancer Treatment Group adjuvant protocol, were studied immunohistochemically. c-erbB2 staining was classified as negative, weak (1+), moderate (2+), or strong (3+) and was assessed for effectiveness as a predictor of outcome in univariate and Cox model multivariate analyses. RESULTS: Twenty percent of specimens exhibited moderate or strong c-erbB2 staining. The median disease free survival period of the strong staining group was 2.9 years, compared with 7.1 years for all other patients (P = 0.01). The median overall survival for the strong staining group was 5 years, compared with 12 years for all other patients (P = 0.03). A definite correlation was noted between degree of nodal involvement and the likelihood of strong c-erbB2 staining (P = 0.001). There was also a significant correlation between c-erbB2 staining and higher nuclear grade and estrogen receptor negativity. In a multivariate analysis, c-erbB2 staining was not a significant predictor of either disease free survival or overall survival. CONCLUSION: According to this analysis, the strong correlation between c-erbB2 expression and degree of nodal involvement, higher grade disease, and estrogen receptor negativity suggests expression of this protooncogene product in a biologically more aggressive form of breast cancer. In a multivariate analysis, c-erbB2 expression was not an independent prognostic factor. Thus, c-erbB2 assessment did not appear to add significantly to the information provided by currently available standard disease parameters.

Measurable or assessable disease in lung cancer trials: does it matter?

PURPOSE: The goals of this study were to analyze and compare the major clinical response rates and survival of patients with either measurable or assessable disease status to treatment with systemic chemotherapy. PATIENTS AND METHODS: All patients had stage IIIB or IV non-small-cell lung cancer (NSCLC) and were enrolled onto three consecutive phase III clinical trials. Patients were stratified by disease status (measurable or assessable) before randomization to systemic chemotherapy. The three trials were conducted in the setting of a multicenter cooperative oncology group. Composite data were obtained for the three trials. Major clinical responses, time to progression, and survival were analyzed and compared in patients with measurable or assessable disease using standard statistical methods. RESULTS: Four hundred twenty-six patients were enrolled onto the three trials from June 1981 through August 1990. Measurable disease was present in 236 patients (55%) and assessable disease in 190 (45%). Each study was well balanced for the number of patients with measurable or assessable disease on either treatment regimen. A major clinical response was observed in 71 patients with measurable disease (30%; 95% confidence interval [CI], 24 to 36). Forty patients with assessable disease responded to treatment (21%; 95% CI, 16 to 28) (P = .04). The time to progression for all patients (P = .23) and for responders only (P = .10) was not significantly different based on disease status. Overall survival and survival of responders only was not significantly different, but patients with assessable disease tended to do better. Using multivariate analysis, sex and disease status had a borderline influence on the major response rate (P = .05). Performance score (PS) was the only factor that was significantly correlated with survival. CONCLUSION: NSCLC patients with assessable disease have major clinical response rates, time to progression, and survival that are similar to those of NSCLC patients with measurable disease. This study supports the inclusion of patients with assessable-disease lung cancer in both phase II and III trials conducted in the cooperative group setting.

Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer.

PURPOSE: We evaluated the effect of recombinant interferon gamma (rIFN-gamma) on survival and toxicity in small-cell lung cancer (SCLC) patients in complete remission (CR). PATIENTS AND METHODS: One hundred patients in CR following treatment with six cycles of combination chemotherapy, thoracic radiotherapy (TRT), and prophylactic cranial irradiation (PCI) were studied. All patients had been enrolled onto a cooperative group trial (North Central Cancer Treatment Group [NCCTG] 86-20-51). Patients received observation only or rIFN-gamma at a dose of 4 x 10(6) U subcutaneously per day for 6 months. RESULTS: Six patients (12%) did not comply with rIFN-gamma treatment. Substantial nonhematologic toxicities consisting of chills, myalgia, lethargy, and alteration of mood-personality were observed. No patient experienced life-threatening or fatal toxicity. The median times to progression for rIFN-gamma treatment or observation were 6.9 and 8.1 months (P = .54). The median survival times were 13.3 and 18.8 months, respectively (P = .43). Approximately 70% of all patients relapsed within 2 years. CONCLUSION: Time to progression and survival were inferior in patients treated with rIFN-gamma compared with randomized control subjects, although this difference was not statistically significant. These data indicate that rIFN-gamma treatment is not associated with a 33% improvement in survival (P = .04). Because of the high rate of relapse, SCLC patients in CR are an ideal group in which to evaluate novel and minimally toxic agents.