Retreatment Interval Research Articles

Stereotactic Radiosurgery for Treatment of Spinal Metastases Recurring in Close Proximity to Previously Irradiated Spinal Cord

As the spinal cord tolerance often precludes reirradiation with conventional techniques, local recurrence within a previously irradiated field presents a treatment challenge. We retrospectively reviewed 51 lesions in 42 patients treated from 2002 to 2008 whose spinal metastases recurred in a previous radiation field (median previous spinal cord dose of 40 Gy) and were subsequently treated with stereotactic radiosurgery (SRS). SRS was delivered to a median marginal dose of 20 Gy (range, 10-30 Gy) in 1-5 fractions (median, 2), targeting a median tumor volume of 10.3 cm(3) (range, 0.2-128.6 cm(3)). Converting the SRS regimens with the linear quadratic model (α/β = 3), the median spinal cord maximum single-session equivalent dose (SSED) was 12.1 Gy(3) (range, 4.7-19.3 Gy(3)). With a median follow-up of 7 months (range, 2-47 months), the Kaplan-Meier local control and overall survival rates at 6/12 months were 87%/73% and 81%/68%, respectively. A time to retreatment of ≤12 months and the combination of time to retreatment of ≤12 months with an SSED of <15 Gy(10) were significant predictors of local failure on univariate and multivariate analyses. In patients with a retreatment interval of <12 months, 6/12 month local control rates were 88%/58%, with a SSED of >15 Gy(10), compared to 45%/0% with <15 Gy(10), respectively. One patient (2%) experienced Grade 4 neurotoxicity. SRS is safe and effective in the treatment of spinal metastases recurring in previously irradiated fields. Tumor recurrence within 12 months may correlate with biologic aggressiveness and require higher SRS doses (SSED >15 Gy(10)). Further research is needed to define the partial volume retreatment tolerance of the spinal cord and the optimal target dose.

Cost-effectiveness modelling of biological treatment sequences in moderate to severe rheumatoid arthritis in France

Modern treatment of RA includes the use of biologics. Their cost is high and comparison between different treatment strategies is needed. Direct medical costs of RA in France were evaluated based on expert opinion. Then, simulation-decision analytical models were developed to assess four biologic treatment sequences over 2 years in patients failing to respond to at least one anti-TNF agent. Effectiveness was expressed in theoretical expected number of days (TEND) in remission or low disease activity [low disease activity score (LDAS)] based on DAS-28 scores. Direct medical costs of RA in France (excluding the cost of biologics) were estimated at euro 905 (s.d. 263) for 6 months and euro 696 (s.d. 240) for each subsequent 6 months (P < 0.001) for patients achieving LDAS and euro 1215 for 6 months (s.d. 405) for patients not achieving LDAS. Based on LDAS criteria, using abatacept after an inadequate response to the first anti-TNF agent (etanercept) appeared significantly (P < 0.01) more efficacious over a 2-year period (102 TEND) compared with using rituximab at a 6-month re-treatment interval (82 TEND). Mean cost-effectiveness ratios showed significantly lower costs (P < 0.01) per TEND with abatacept as second biologic agent (euro 278) compared with rituximab (euro 303). After an inadequate response to two anti-TNF agents, using abatacept also appeared significantly more efficacious than an anti-TNF agent (P < 0.01). All comparisons were confirmed when using remission criteria instead of LDAS. Advanced simulation models based on clinical evidence and medical practice appear to be a promising approach for comparing cost-effectiveness of biologic strategies in RA.

Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients With Prior Pelvic Irradiation

To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >or=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy. Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of <or=2 years (p = 0.001). Hyperfractionated, accelerated reirradiation was well tolerated, with low rates of acute toxicity and moderate rates of late toxicity. Reirradiation may help improve pelvic control in rectal cancer patients with a history of pelvic radiotherapy.

Combination Therapy for Wet Age-related Macular Degeneration

Increasing appreciation of the complexity of the wet type of age-related macular degeneration (AMD) has made combination therapy an area of current intense interest. Administered in dual or triple combinations, the current therapeutic mainstays ߝ corticosteroids, verteporfin photodynamic therapy (V-PDT) and inhibitors of vascular endothelial growth factor (VEGF) ߝ have more potential to successfully treat the various pathogenetic factors contributing to wet AMD than any single-therapy approach. The different mechanisms of action involved in combination therapy are intended to reduce inflammation, eradicate current and future choroidal neovascularisation and lessen VEGF expression. Evidence from clinical trials demonstrates visual acuity benefits, lower re-treatment rates and longer treatment-free intervals with combination therapies compared with monotherapies. This article summarises the rationale and the clinical evidence that support the use of double and triple combination therapy in wet AMD.

Long-term control of choroidal neovascularisation secondary to angioid streaks treated with intravitreal bevacizumab (Avastin)

Aim:To evaluate the efficacy of intravitreal bevacizumab (IB) in the long-term control of subfoveal choroidal neovascularisation (CNV) associated with angioid streaks (AS).Methods:Patients with unilateral active CNV associated with AS were...

Analysis of the pattern of hypersensitivity reactions in patients receiving carboplatin retreatment for recurrent ovarian cancer

The aim of this paper was to assess hypersensitivity reactions in 69 patients who received carboplatin (CBDCA) retreatment for recurrent ovarian cancer. Hypersensitivity reactions developed in 15 (21.7%) patients and occurred during the second cycle of retreatment in 13 (86.7%) of them. Reactions consisted of skin rash, flushing, itching, or abdominal cramping in eight (53.3%) and severe respiratory or cardiovascular events in seven patients (46.7%). One patient had a chest pain, without any other symptoms suggestive of hypersensitivity, followed by cardiac arrest unresponsive to standard resuscitative measures. All the other cases promptly recovered from symptoms. Logistic regression analysis showed that allergy history and CBDCA retreatment interval (interval time between the last cycle of first-line chemotherapy and CBDCA retreatment) were independent predictive variables for the risk of hypersensitivity, whereas patient age, first-line chemotherapy, total CBDCA dose given during first-line treatment, recurrence treated with CBDCA (first versus other), and CBDCA regimen at recurrence had no predictive value. Hypersensitivity reaction rate was higher in patients with CBDCA retreatment interval longer than 23.4 months compared to those with a shorter interval (36.3% versus 8.3%,P= 0.0132). Nine patients were subsequently treated with cisplatin, and two (22.2%) still developed allergic reactions. In conclusion, hypersensitivity reactions to CBDCA retreatment can occur in approximately one fifth of the cases, and a CBDCA retreatment interval longer than 2 years appears to be the strongest predictive variable for the development of allergic reactions.

Thinning and prescribed fire effects on dwarf mistletoe severity in an eastern Cascade Range dry forest, Washington

Forest thinning and prescribed fire practices are widely used, either separately or in combination, to address tree stocking, species composition, and wildland fire concerns in western US mixed conifer forests. We examined the effects of these fuel treatments alone and combined on dwarf mistletoe infection severity immediately after treatment and for the following 100 years. Thinning, burning, thin + burn, and control treatments were applied to 10 ha units; each treatment was replicated three times. Dwarf mistletoe was found in ponderosa pine and/or Douglas-fir in all units prior to treatment. Stand infection severity was low to moderate, and severely infected trees were the largest in the overstory. Thinning produced the greatest reductions in tree stocking and mistletoe severity. Burning reduced stocking somewhat less because spring burns were relatively cool with spotty fuel consumption and mortality. Burning effects on vegetation were enhanced when combined with thinning; thin + burn treatments also reduced mistletoe severity in all size classes. Stand growth simulations using the Forest Vegetation Simulator (FVS) showed a trend of reduced mistletoe spread and intensification over time for all active treatments. When thinned and unthinned treatments were compared, thinning reduced infected basal area and treatment effects were obvious, beginning in the second decade. The same was true with burned and unburned treatments. Treatment effects on infected tree density were similar to infected basal area; however, treatment effects diminished after 20 years, suggesting a re-treatment interval for dwarf mistletoe.

Analysis of the pattern of hypersensitivity reactions in patients receiving carboplatin retreatment for recurrent ovarian cancer

The aim of this paper was to assess hypersensitivity reactions in 69 patients who received carboplatin (CBDCA) retreatment for recurrent ovarian cancer. Hypersensitivity reactions developed in 15 (21.7%) patients and occurred during the second cycle of retreatment in 13 (86.7%) of them. Reactions consisted of skin rash, flushing, itching, or abdominal cramping in eight (53.3%) and severe respiratory or cardiovascular events in seven patients (46.7%). One patient had a chest pain, without any other symptoms suggestive of hypersensitivity, followed by cardiac arrest unresponsive to standard resuscitative measures. All the other cases promptly recovered from symptoms. Logistic regression analysis showed that allergy history and CBDCA retreatment interval (interval time between the last cycle of first-line chemotherapy and CBDCA retreatment) were independent predictive variables for the risk of hypersensitivity, whereas patient age, first-line chemotherapy, total CBDCA dose given during first-line treatment, recurrence treated with CBDCA (first versus other), and CBDCA regimen at recurrence had no predictive value. Hypersensitivity reaction rate was higher in patients with CBDCA retreatment interval longer than 23.4 months compared to those with a shorter interval (36.3% versus 8.3%, P = 0.0132). Nine patients were subsequently treated with cisplatin, and two (22.2%) still developed allergic reactions. In conclusion, hypersensitivity reactions to CBDCA retreatment can occur in approximately one fifth of the cases, and a CBDCA retreatment interval longer than 2 years appears to be the strongest predictive variable for the development of allergic reactions.

Microbial larvicides for malaria control in The Gambia

BackgroundMosquito larval control may prove to be an effective tool for incorporating into integrated vector management (IVM) strategies for reducing malaria transmission. Here the efficacy of microbial larvicides against Anopheles gambiae s.l. was tested in preparation for a large-scale larviciding programme in The Gambia.MethodsThe impact of water-dispersible (WDG) and corn granule (CG) formulations of commercial Bacillus sphaericus strain 2362 (Bs; VectoLex®) and Bacillus thuringiensis var.israelensis strain AM65-52 (Bti; VectoBac®) on larval development were tested under laboratory and field conditions to (1) identify the susceptibility of local vectors, (2) evaluate the residual effect and re-treatment intervals, (3) test the effectiveness of the microbials under operational application conditions and (4) develop a method for large-scale application.ResultsThe major malaria vectors were highly susceptible to both microbials. The lethal concentration (LC) to kill 95% of third instar larvae of Anopheles gambiae s.s. after 24 hours was 0.023 mg/l (14.9 BsITU/l) for Bs WDG and 0.132 mg/l (396 ITU/l) for Bti WDG. In general Bs had little residual effect under field conditions even when the application rate was 200 times greater than the LC95. However, there was a residual effect up to 10 days in standardized field tests implemented during the dry season. Both microbials achieved 100% mortality of larvae 24–48 hours post-application but late instar larvae were detected 4 days after treatment. Pupae development was reduced by 94% (95% Confidence Interval = 90.8–97.5%) at weekly re-treatment intervals. Field tests showed that Bs had no residual activity against anopheline larvae. Both microbials provided complete protection when applied weekly. The basic training of personnel in identification of habitats, calibration of application equipment and active larviciding proved to be successful and achieved full coverage and control of mosquito larvae for three months under fully operational conditions.ConclusionEnvironmentally safe microbial larvicides can significantly reduce larval abundance in the natural habitats of The Gambia and could be a useful tool for inclusion in an IVM programme. The costs of the intervention in this setting could be reduced with formulations that provide a greater residual effect.

FIELD TRIALS WITH TANK MIXTURES OF BACILLUS THURINGIENSIS SUBSP. ISRAELENSIS AND BACILLUS SPHAERICUS FORMULATIONS AGAINST CULEX PIPIENS LARVAE IN SEPTIC TANKS IN ANTALYA, TURKEY

Efficacy of tank mixtures of commercial Bacillus thuringiensis subsp. israelensis (Bti) and Bacillus sphaericus (Bs) water-dispersable granule (WDG) formulations was evaluated in septic tanks, against Culex pipiens L. (Diptera: Culicidae) larvae. VectoLex WDG (Bs) + VectoBac WDG (Bti) were evaluated at various ratios from 488 g/ha VectoLex + 250 g/ha VectoBac up to 3,000 g/ha of each. All applications and ratios delivering VectoLex WDG at a rate equal to or greater than 988 g/ha provided more than 90% control for 28 days after treatment. The lowest dose provided this level of control for at least 7 days after treatment, with greater than 80% control after 2 wk. These results suggest that a retreatment interval of 2 wk is recommended with the lowest dose and retreatment intervals of 4 or more wk are recommended with the doses equal to or higher than 988 g/ha VectoLex + 250 g/ha VectoBac.

Ages for the Big Stone Moraine and the oldest beaches of glacial Lake Agassiz: Implications for deglaciation chronology

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ANECORTAVE ACETATE TREATMENT FOR RETINAL ANGIOMATOUS PROLIFERATION

The purpose of this study was to evaluate anecortave acetate treatment of retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration, with specific regard to inhibition of neovascularization and maintenance of vision. Thirty-four patients with RAP with any stage of neovascularization were randomized 1:1:1 for treatment with three different quantities (30 mg, 15 mg, 3 mg) of anecortave acetate sterile suspension for juxtascleral administration. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study chart), intraocular pressure measurement, biomicroscopy, funduscopy, digital fluorescein, and indocyanine green angiography were recorded at baseline and at 3 months. A 6-month retreatment interval was established for this study with a follow-up of 12 months. In selected patients optical coherence tomography was performed. The outcomes were mean changes in visual acuity and lesion size at 1 year. The detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes, but all neovascular lesions increased in size. Vision loss occurred in the majority of study eyes (22 out of 34 eyes, 64.7%) independent of the concentration administered. The results suggest that a posterior juxtascleral injection of anecortave acetate reduces capillary permeability in patients with RAP. However, in spite of improvement of the exudation there is a progression of neovascularization and a significant loss of vision in all these patients. Like other monotherapeutic methods used to treat this variant of neovascular age-related macular degeneration, anecortave acetate alone does not appear to benefit these patients. Future studies should investigate a combination form of therapy.

Retreatment Tolerance of Normal Tissues.

The experimental data for reirradiation of various normal tissues are reviewed. Retreatment tolerance is discussed in relation to the interval between treatments and the initial treatment dose delivered. To facilitate a comparison between tissues with different radiosensitivities, both initial and retreatment doses are described in terms of percent extrapolated tolerance dose, using linear-quadratic fraction concepts. The data indicate that rapidly dividing tissues, such as skin and intestine, recover rapidly and can be reirradiated to almost full tolerance within 1 to 3 months. Some slowly dividing tissues, eg, lung and spinal cord, are capable of a more limited long-term recovery and can be reirradiated with partial tolerance doses. For these tissues, reirradiation tolerance increases with time between treatments and is inversely related to the initial dose. In other tissues, eg, bladder, the reirradiation tolerance is independent of retreatment interval suggesting permanent residual injury. In the kidney, reirradiation tolerance actually decreases with time, indicative of further progression of subclinical damage from the first treatment.

Resolution and resurgence of schistosoma haematobium-induced pathology after community-based chemotherapy in ghana, as detected by ultrasound.

Community-based treatment is recommended for endemic populations with urinary schistosomiasis; however, the optimal target group for treatment and retreatment interval have not been established. Using ultrasound, this study identified subpopulations whose lesions were most likely to respond to treatment and characterized resurgence of pathology. Ultrasound examination of 1202 infected patients was followed by chemotherapy with praziquantel. A sample of 698 patients was followed for 18 months after treatment. Nearly all types of bladder pathologies resolved after treatment, regardless of patient's age or intensity of initial infection. However, many patients' upper urinary tract pathologies (62.5%) did not resolve. During the 18-month follow-up period, reappearance of severe bladder pathologies was rare, and <10% of persons had resurgence of mild bladder pathologies. For this population, retreatment is not needed annually but might be cost effective if given several years later. Confirmation from other areas is required before general policies can be formed.

Glacier Fluctuations in the Kenai Fjords, Alaska, U.S.A.: An Evaluation of Controls on Iceberg-Calving Glaciers

The histories of four iceberg-calving outlet-glacier systems in the Kenai Fjords National Park underscore the importance of fiord depth, sediment supply, and fiord geometry on glacier stability. These parameters, in turn, limit the reliability of calving glacier chronologies as records of climatic change. Tree-ring analysis together with radiocarbon dating show that the Northwestern and McCarty glaciers, with large drainage basins, were advancing in concert with nearby land-terminating glaciers about A.D. 600. After an interval of retreat and possible nonclimatically induced extension during the Medieval Warm Period, these ice margins advanced again through the Little Ice Age and then retreated synchronously with the surrounding land-terminating glaciers about A.D. 1900. In contrast, Holgate and Aialik glaciers, with deeper fiords and smaller basins, retreated about 300 yr earlier. Reconstructions of Little Ice Age glaciers suggest that equilibrium-line altitudes of Northwestern and McCarty glaciers were, respectively, 270 and 500 m lower than now. Furthermore, the reconstructions show that these two glaciers were climatically sensitive when at their terminal moranies. However, with ice margins at their present recessional positions and accumulation area ratios between 0.8 and 0.9, only McCarty Glacier shows evidence of advance. Aialik and Holgate glaciers were climatically insensitive during the Little Ice more » Age maxima and remain insensitive to climate. 40 refs., 7 figs., 2 tabs. « less

Options for liming rivers to ameliorate acidity ? A UK perspective

The options for large scale liming of river systems are reviewed with particular reference to the River Tywi in Wales, a major salmonid river with a reservoir in the upper catchment. For hydrological source area liming the cost of lime transport is high due to remoteness and inaccessibility. The concern of potential damage to wetland mires of conservation value is considered. Re-treatment intervals are expected to be 5–10 years, but results from sub-catchment experiments indicate that treatment longevity and the pattern of ecological recovery are uncertain. Flow-related dosing systems for rivers avoid impacts on wetlands but would treat only the main river. Reliability may be problematical though the reservoir provides a margin of safety against system failure. Reservoirs can be limed to treat the main river outflow. This avoids the problems of power supply. For the River Tywi, the financial costs of both direct treatment methods are lower than for catchment liming and comparable with estimates of the economic benefit to the fishery. The system currently operated on the Tywi is reservoir treatment. Results from the first 3 years demonstrate colonization of the main river by acid intolerant invertebrate taxa and clear increases in populations of juvenile Atlantic salmon, Salmo salar L. and sea/brown trout. Salmo trutta L.

Retreatment tolerance of normal tissues

The experimental data for reirradiation of various normal tissues are reviewed. Retreatment tolerance is discussed in relation to the interval between treatments and the initial treatment dose delivered. To facilitate a comparison between tissues with different radiosensitivities, both initial and retreatment doses are described in terms of percent extrapolated tolerance dose, using linear-quadratic fraction concepts. The data indicate that rapidly dividing tissues, such as skin and intestine, recover rapidly and can be reirradiated to almost full tolerance within 1 to 3 months. Some slowly dividing tissues, eg, lung and spinal cord, are capable of a more limited long-term recovery and can be reirradiated with partial tolerance doses. For these tissues, reirradiation tolerance increases with time between treatments and is inversely related to the initial dose. In other tissues, eg, bladder, the reirradiation tolerance is independent of retreatment interval suggesting permanent residual injury. In the kidney, reirradiation tolerance actually decreases with time, indicative of further progression of subclinical damage from the first treatment.

Promotion of flowering in Engelmann-white spruce seed orchards by GA 4/7 stem injection: effects of site, clonal fecundity, girdling and NAA, and treatment carry-over effects

Stem injections of gibberellin A 4/7 (GA 4/7) and girdling were tested in factorial combination on good- and poor-flowering clones of Engelmann-white spruce in two seed orchards on the same site with different levels of past cone production. A second study compared one vs. two injections of GA 4/7 (same total dosage), the latter with and without the auxin naphthaleneacetic acid (NAA). In both years and both orchards, GA 4/7 alone promoted abundant seed and pollen cones, but treatment was relatively more effective on good-flowering clones and in the more productive orchard. Still, treatment improved the orchard parental balance in that without treatment, 80% of the seed cones were produced by only 10–17% of the clones, compared to 43% of the clones with GA 4/7. Flowering response to GA 4/7 was independent of number of injections and addition of NAA. Girdling was ineffective by itself in flowering promotion but enhanced the female response to GA 4/7 in the less-productive orchard and the male response by poor-flowering clones. Gibberellin A 4/7 treatment in 1988 had a slight adverse carry-over effect on tree condition and level of flowering in 1990, although this may be a consequence of heavy cone-bearing in 1989. Gibberellin A 4/7 stem injection is practical, but the optimal retreatment interval necessary for vegetative recovery and sustained abundant cone production remains to be established.

Two-year follow-up of Schistosoma mansoni infection and morbidity after treatment with different regimens of oxamniquine and praziquantel

Three study groups in the Rusizi plain (Burundi) were examined parasitologically (duplicate 28 mg Kato slides) and clinically (history, abdominal palpation) 0, 1·5, 3, 6, 12 and 24 months after treatment for Schistosoma mansoni infection. Infected subjects in Maramvya (n = 430) were treated randomly with oxamniquine 20, 30 or 40 mg/kg; those in Bulinga (n = 457) with praziquantel, 20, 30 or 40 mg/kg; those in Bulamata (n = 333) with praziquantel, 30 or 40 mg/ kg. In children (<20 years) in Maramvya and Bulamata, infection rates and intensities returned almost to pretreatment levels one to 2 years after treatment. In Bulinga, reinfection in children was much less intense. Hardly any reinfection occurred in adults in Bulinga and Maramvya; in Bulamata, half of the cured adults were reinfected, most of them lightly, 2 years after treatment. The initial parasitological advantage of the higher dosages of both drugs disappeared generally 3–12 months after treatment. There was no indication of predisposition to heavy reinfection after treatment of subjects with initial high egg counts. Little relation between pre-treatment egg count and morbidity was observed. The impact of chemotherapy on hepatomegaly was limited and observed only in adults treated with 40 mg/kg of either drug. Spleen rates in children and adults were not affected. Abdominal pain was reduced in almost all treatment groups for 3 to 24 months. The frequency of bloody diarrhoea decreased dramatically in children and adults from all 3 villages. This effect lasted 24 months in Maramvya, 12 months in Bulinga and 6 months in Bulamata, and was not dose-dependent. It is concluded that: (i) repeated population chemotherapy combined with sanitation is necessary to achieve lasting impact on infection rates; (ii) retreatment intervals should be adapted to age group and, possibly, local endemicity levels; (iii) the morbidity impact of population chemotherapy in these conditions was greater on intestinal than on hepatosplenic disease; (iv) lower, cheaper treatment schedules may in the long term be as effective as those with high cure rates.

Residual radiation damage in murine lung assessed by pneumonitis

The amount of radiation damage remaining in mouse lung has been assessed by retreatment from 1 to 6 months after a range of first doses. Pneumonitis at 196 days after retreatment was used as the endpoint. Lungs were first irradiated with a range of single doses (6–10 Gy). Ten Gy was the highest dose that, on its own, produced no changes in breathing rate or deaths due to pneumonitis. One to 6 months later lungs were retreated with a full range of single doses. Isoeffect doses were calculated for lethality for all retreatment times after each priming dose. The amount of residual damage remaining in the lung has been calculated as both a proportion of first doses and as the effect equivalent of remembered dose. Following a 10 Gy first dose, there was evidence of remembered irradiation injury at all retreatment intervals. After a 6 Gy priming dose, the lungs could be retreated to tolerance. The amount of residual damage was proportional to the size of first dose and was highest at 1 month (27% after 6 Gy and 70% after 10 Gy) and lowest after 3 months (0% after 6 Gy and 46% after 10 Gy). This partial recovery of lung function between 1 and 3 months was followed by an increase in amount of damage “remembered”; that is, a reduction in the retreatment dose that could be delivered. The proportion of residual damage after 10 Gy was never less than 25%. The data suggest an early target cell depletion and regeneration in the lung (within 3 months), the extent of which is dependent on the size of initial injury.