Medication of Diseases News - Part 9

Anatomic Evaluation of Postural Bronchial Drainage of the Lung With Special Reference to Patients With Tracheal Intubation

Anatomic Evaluation of Postural Bronchial Drainage of the Lung With Special Reference to Patients With Tracheal IntubationSeveral sequences of specific postures, each corresponding to a particular lung segment, have been recommended for therapeutic bronchial drainage (Table 1; Fig 1, left, A through F). Miyagawa revised and rearranged these postures for patients with tracheal intubation, and recommended a sequence comprising the supine, prone, and 45° rotative prone with left-side-up and right-side-up positions (Table 1; Fig 1, right, G through I); this method has been generally accepted for intensive care patients in Japan, although it is not familiar in other countries. In addition to this sequence, inclusion of the prone position has been recommended to improve ventilation-perfusion relationships in the dorsal lung segments in patients with tracheal intuba-tion. comments

Extracranial Stereotactic Radioablation: Conclusion

Extracranial Stereotactic Radioablation: ConclusionIntuitively, both toxicity and local failure after a given dose of radiation would be expected to be greater for treating larger T2 tumors compared to T1 tumors. In our study, T1 and T2 tumors were treated within separate dose-escalation groups. We did not observe any obvious differences in toxicity or local failure between the T-stage groups. However, our study was neither designed nor powered to detect such differences. While it is likely that larger tumors will both be more difficult to control and that patients with such tumors will be at higher risk for treatment-related toxicity, further study will be required to quantify any difference.

Extracranial Stereotactic Radioablation: Respiratory toxicity

While radiation pneumonitis appeared less frequently in this trial than might have been predicted, radiation damage to the lung was still apparent. Repeat imaging studies (ie, CT scans and CXRs) in the majority of patients revealed new fibrotic changes posttherapy. These changes typically assumed a wedge or triangular shape, with the apex occurring at the site of the treated tumor and extending laterally toward the chest wall. In all likelihood, these imaging changes correspond to the collapse of the lung distal to the airway passages near the treated tumor. These airway passages (bronchioles) would likely be severely damaged by the ESR treatment with sloughing of epithelium, stenosis, and blocking of the downstream airway. Perhaps the resulting loss of functioning pulmonary tissue explains the measured decline in pulmonary function test results (particularly Dlco and Po2) for some of the treated patients. However, for our patients with mostly peripheral lesions, the loss of lung did not correspond to significant respiratory compromise. According to the radiobiological models describing injury to various architectural arrangements of normal tissues described by Wolbarst et al and Yeas and Kalend, however, the same treatment given to central lesions near serially functioning major bronchi could result in significant respiratory toxicity. canadian health & care mall

Extracranial Stereotactic Radioablation: Dysfunction

Extracranial Stereotactic Radioablation: DysfunctionModels predicting radiation-induced pulmonary toxicity have used conventional lung fields treated with standard fractionated radiation as their input data and, typically, have described pulmonary toxicity in relation to the volume of lung receiving or exceeding a specified dose. Prescription dose volumes in conventional fractionated RT are generally much larger than those for the ESR techniques described in this article. The geometric dose distribution for conventional RT is more polygonal, as opposed to spherical or stellate for ESR. Furthermore, the biological effect on both normal tissue and tumor tissue after treatment with very large doses per fraction would be expected to be much different than that observed with standard fractionated radiation. Dose-conversion models, such as the linear quadratic model proposed by Douglas and Fowler, may be applicable to the lower dose ranges used in this study, but will likely overpredict the potency of the therapy at high doses per fraction. In addition, these models do not directly account for an anatomic location of injury as it relates to overall organ dysfunction. More info

Extracranial Stereotactic Radioablation: Discussion

Seven patients died of what the investigators determined to be comorbid medical problems without cancer recurrence. Of these seven patients, five died of noncardiopulmonary dysfunction (ie, broken hip, prostate cancer, renal failure due to outlet obstruction, renal failure due to hepatorenal syndrome, and pancreatic cancer). The other two died of cardiopulmonary problems that were thought by the investigators to be unrelated to the therapy (ie, lower extremity deep venous thrombosis with pulmonary embolism and progressive idiopathic pulmonary fibrosis diagnosed prior to the protocol treatment). No autopsy was performed to verify the actual cause of death in any patient. The Kaplan-Meier disease-free survival rate and the overall survival rate at the median time of follow-up (15.2 months) were 50% and 64%, respectively. read only

Extracranial Stereotactic Radioablation: Occurrence of Toxicity

Extracranial Stereotactic Radioablation: Occurrence of ToxicityThe timing of the observed toxicity, dose-limiting or not, preceded 6 weeks from the end of treatment in all cases. Patients continued to be observed for toxicity, but with a median follow-up period of 15.2 months (range, 2 to 30 months), no late toxicity attributed to the therapy has been identified.
Response
The tumors of nearly all patients responded to therapy. The extent of tumor response was difficult to measure in many cases due to the appearance of postradiation fibrotic changes (described earlier). In cases in which postradiation fibrotic changes could not be distinguished from residual tumor, it was assumed that the response was incomplete. With this caveat, the partial and complete response rates were 60% and 27%, respectively. The percentage of complete responses for patients receiving doses of < 1,600 cGy per fraction was not appreciably different from those who received doses of > 1,600 cGy per fraction. Figure 3 shows an example of a favorable response. further

Extracranial Stereotactic Radioablation: Other Toxicity

The treatment included abdominal compression to minimize respiratory movement. The clamping action on the abdomen near the anterior inferior costal margin resulted in chest wall tenderness and discomfort, requiring treatment with over-the-counter analgesics in several patients. This subsided within days of the end of therapy in all cases. There was no esophageal toxicity. At the highest dose levels, a single patient experienced grade 3 radiation dermatitis with skin redness, peeling, and discomfort along the entrance trajectory of each treatment beam. This skin irritation occurred 2 to 3 weeks after the completion of therapy. The patient admitted to purposefully sun-tanning in Mexico (against medical advice) prior to the onset of this skin toxicity. itat on

Extracranial Stereotactic Radioablation: Cardiopulmonary Toxicity

Extracranial Stereotactic Radioablation: Cardiopulmonary ToxicityCardiac toxicity, which manifested as an asymptomatic pericardial effusion seen on a CT scan, occurred in one patient. Symptoms of radiation pneumonitis that were followed up prospectively included fatigue, fever, shortness of breath, nonproductive cough, and pulmonary infiltrates seen on a CXR. Fatigue was reported in every patient, and fever was reported in none. Six patients reported worsening shortness of breath and nonproductive cough, and were treated with steroids, inhalers, cough medicines, and oxygen therapy. One patient had worsening pulmonary infiltration seen on CXRs or CT scans. Worsening fibrotic changes appeared on CXRs or CT scans in 25 patients. These fibrotic changes were generally limited to a small fraction of total lung volume, extending peripherally starting at the location of the treated tumor.

Extracranial Stereotactic Radioablation: Statistical Analysis

Follow-up was determined from the date of the last stereotactic treatment, not from the date of diagnosis, to determine the median follow-up and Kaplan-Meier time-to-event estimates of survival data. Paired data sets from pulmonary function tests prior to and after the treatment were compared using a paired two-tailed t test. Statistical significance was defined as a p value of < 0.05.
Results
Thirty-seven patients (23 men and 14 women) with a median age of 75 years (range, 56 to 91 years) were enrolled into the study. Patient characteristics are listed in Table 1. The most common characteristic making a patient ineligible for surgery was a baseline FEV1 of < 40% predicted, which was identified in 17 patients. Other medical problems making the patients poor surgical candidates included severe heart disease (11 patients), pulmonary fibrosis (5 patients), severe diabetes (2 patients), peripheral vascular disease (1 patient), and liver cirrhosis (1 patient). Eleven of the patients enrolled required supplemental home oxygen therapy prior to receiving the treatment. More info

Extracranial Stereotactic Radioablation: Dosage and Dose Escalation

Extracranial Stereotactic Radioablation: Dosage and Dose EscalationThe starting dose for the trial was 800 cGy, prescribed to the 80% isodose volume per fraction for a total of three fractions (total dose, 2,400 cGy). According to protocol guidelines, the fractions were to be separated by a minimum of 2 days and a maximum of 8 days, but no more than two fractions per week.
Subsequent cohorts of patients on the trial received an additional 200 cGy per treatment (total, 600 cGy per increment) at each dose-escalation step. A minimum of three patients was accrued for each specified dose level. If two or more of the patients experienced DLT, as defined above, the MTD would be considered to have been exceeded. If DLT was experienced in one of the three patients, an additional two patients would be accrued at that dose level. If no additional DLT was noted in the additional two patients within a minimum observation period (ie, four of five patients free of severe toxicity), dose escalation to the next dose level would proceed. Otherwise, if one or more of the additional two patients experienced DLT, the MTD would be considered to have been exceeded. Reading here

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