Purpose:
To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve ...locoregional control and ultimately survival.
Methods and Materials:
The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2–T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II.
Results:
As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%,
p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%,
p = 0.04), disease-free survival (33% vs. 21%,
p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%,
p < 0.0001), and cause-specific mortality (23% vs. 31%,
p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2–6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%,
p = 0.015). In patients with Gleason 7–10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival.
Conclusion:
In patients with Gleason score 2–6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.
Purpose: To determine the potential advantage of androgen ablation following standard external-beam radiation therapy in patients with locally advanced (clinical or pathologic T3; clinical or ...pathologic node positive) carcinoma of the prostate.
Methods and Materials: In 1987 the RTOG initiated a Phase III trial of long-term adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients were accrued to the study of which 945 remain analyzable: 477 on the adjuvant hormone arm (Arm I); and 468 on the radiation only arm (Arm II) with hormones initiated at relapse. The initial results were reported in the
Journal of Clinical Oncology in 1997.
Results: With a median follow up of 5.6 years for all patients and 6.0 years for living patients local failure at 8 years was 23% for Arm I and 37% for Arm II (
p < 0.0001). Distant metastasis was likewise favorably impacted with the immediate use of hormonal manipulation with a distant metastasis rate in Arm I of 27% and 37% in Arm II (
p < 0.0001). Disease-free survival (NED survival) and NED survival with PSA of 1.5 ng/mL (bNED) or less were both statistically significant in favor of the immediate hormone arm (both
p < 0.0001). Cause-specific failure was not statistically different with a cause-specific failure of 16% for Arm I and 21% in Arm II (
p = 0.23). Overall survival was likewise not statistically different between two arms, with a 49% overall survival at 8 years in Arm I and 47% in Arm II (
p = 0.36). Subset analysis of centrally reviewed Gleason 8–10 patients who did not undergo prostatectomy showed that for patients receiving radiation therapy plus adjuvant hormones there was a statistically significant improvement in both absolute (
p = 0.036) and cause-specific survival (
p = 0.019).
Conclusions: Use of long-term adjuvant androgen deprivation in addition to definitive radiation therapy results in a highly significant improvement in regards to local control, freedom from distant metastasis, and biochemical free survival in unfavorable prognosis patients with carcinoma of the prostate.
Films containing antibacterial compounds could be used for packaging perishable foods such as fresh fish and meat for sea freighting over long distances. However, existing commercialised options ...(films with nanosilver zeolites or wasabi extract) are only permitted for food contact in certain regions and films containing alternative antibacterial ingredients are required e.g. for exports to Europe. Certain non-volatile phenolic plant extracts have shown promising antibacterial activity against a wide range of foodborne bacteria in in vitro assays and when integrated in coatings for perishable foods such as fish and meat. Extracts rich in gallotannins tend to show stronger antibacterial effects than other phenols such as flavonoids. Such extracts could be coated onto commercial barrier films by means of flexographic printing—a more industrially feasible option than rod coating or solvent casting typically used in antibacterial coating research. The goal of the present work was to investigate the antibacterial effect of printed latex coatings containing extracts rich in gallotannins and other types of phenolic compounds against 16 common spoilage and pathogenic bacteria of fish and meat. The largest zones of inhibition in disk diffusion assays were obtained with plastic films with coatings containing tannic acid alone, followed by tannic acid with phenolic-rich extracts of feijoa skin or mango seed. Significant inhibition was seen for all bacteria. This study shows that coatings with gallotannins as the main active ingredient can be printed onto commercial barrier films to control the bacteria that limit the shelf-life of fresh fish and meat.
Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated.
In 1987, ...the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm.
Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03).
Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.
The increasing usage of petroleum-based compounds has prompted numerous environmental concerns. Consequently, there has been a steady rise in research on the synthesis of useful materials from ...natural sources. Paper technologists are seeking environmentally acceptable dry end and wet end additives. Among the bio-based resources available, nanocellulose is a popular sustainable nanomaterial additive in the paper industry because of its high strength, high oxygen barrier performance, low density, great mechanical properties, and biocompatibility. NC’s extensive hydroxyl groups provide a unique possibility to dramatically modify the hydrophilicity and charge of the surface in order to improve their potential applications in the paper industry. The current paper reviews two series of surface modifications, each with various subcategories, depending on why modified nanocellulose is added in the paper production: to improve barrier properties or to improve mechanical properties of packaging materials. The methods presented in this study use the minimum amount of chemically hazardous solvents to have the least impact on the environment. This review focuses on modifications of nanocellulose and their subsequent application in the papermaking. The knowledge and the discussion presented in this review will form a literature source for future use by various stakeholders and the sustainable paper manufacturers.
DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy ...(RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus short-course (approximately 4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB).
The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival.
DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation.
Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.
Between July 1987 and September 1991 a program of external beam radiation and synchronous, radiopotentiating chemotherapy was employed to treat 25 women with locoregionally advanced or locoregionally ...recurrent squamous cancer of the vulva. Of 18 previously untreated patients, 1 was Stage II, 10 were Stage III, 6 were Stage IVA, and 1 was Stage IVB. Reasons for patient referral for nonsurgical management included the presence of initially unresectable disease (5 patients), disease extent which would have necessitated partial or total exenteration if treated surgically (9 patients), disease extent predictive of inadequate surgical margins (less than 1 cm gross margin) if treated by less than exenterative surgery (8 patients), and severe comorbid illness precluding surgical management (3 patients). Complete clinical response was obtained in 16 of 18 previously untreated patients (89%) and in 4 of 7 patients with recurrent disease following vulvar surgery (57%). Of 20 patients achieving a complete clinical response, 3 patients have relapsed within the irradiated volume at 11, 38, and 48 months following completion of treatment. Fourteen patients remain alive and continuously cancer free from 2-52 months after completion of treatment (median follow-up 24 months). This experience suggests that initial management with radiation and chemotherapy may offer some patients with locally advanced squamous cancer of the vulva an alternative to exenterative surgery and may hold curative potential for some patients with surgically unresectable or medically inoperable disease.
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