Small cell lung cancer survival rate stage 1,blind man two blue pills two red pills,b.ed rules for deputed teachers in west bengal university,icd 9 code for diabetic erectile dysfunction zoloft - Plans Download

31.03.2015
Amrubicin failed to improve survival over topotecan as second-line therapy for patients with sensitive small-cell lung cancer (SCLC), according to results of a new randomized phase III trial.
Although results are promising, they have confirmed the phase 3 study, which was already underway in 8 countries.
Regarding the treatment of non small cell cancer, the current protocol consists of surgical resection followed by chemotherapy or radiation therapy for cancers IA, B, II A, B. ABSTRACT: Small cell lung cancer (SCLC) accounts for approximately 20% of all cases of lung cancer. Patients with SCLC are classified as having either limited- or extensive-stage disease according to the system developed by the Veteran's Administration Lung Cancer Study Group.[4] Patients with tumors that can easily be encompassed within an acceptable radiation portal (historically defined as a hemithorax) are classified as having limited disease, and they represent approximately one-third of all new SCLC cases. The purpose of this paper is to provide an overview of the clinical presentation, diagnosis, and treatment of brain metastases in patients with SCLC, with a focus on current trends and developments in the treatment of this disease. Brain metastases most frequently arise at the junction between the white and grey matter, or the so called "watershed area" of the brain.[8] The signs and symptoms are not specific to the disease but rather reflect the location and number of metastatic lesions. The diagnosis of brain metastases is based on patient history, neurologic examination, and diagnostic imaging. In fact, SCLC is the most common histologic type of cancer associated with neurologic paraneoplastic syndromes.[ 9] These syndromes are thought to be related to an autoimmune process in which the tumor produces substances that are similar to those normally expressed by the nervous system.
Although patients with brain metastases have a poor prognosis overall, certain factors have been identified that are predictive for an improved outcome.
Brain metastases require prompt intervention to minimize progressive neurologic injury.[10] The aim of initial management is to control increased intracranial pressure if it is present. Although brain metastases from SCLC can cause significant morbidity, it is rarely the sole cause of death. The largest series documenting the role of WBRT in SCLC was reported in 1988 by Carmichael et al, who performed a retrospective review of 59 patients with proven brain metastases from SCLC treated with therapeutic irradiation from 1977 through 1983.[18] Although patients were treated with varying chemotherapy regimens, all those with brain metastases at presentation were given induction chemotherapy. The European Organization for Research and Treatment of Cancer (EORTC) conducted a prospective, phase II study between 1989 and 1995 that accrued 22 patients with SCLC and brain-only metastases to evaluate the efficacy of WBRT as a single treatment modality.[23] Radiation consisted of 30 Gy in 10 fractions to the whole brain.
Many prospective trials have been conducted to identify the optimal dose and fractionation schedule in the treatment of patients with brain metastases. RTOG 9104 was a phase III study comparing accelerated hyperfractionation with standard accelerated fractionation in 429 patients with unresected brain metastases.[29] In this study, 39 patients had SCLC. Wong et al reported on the Mayo Clinic experience with reirradiation for brain metastases.[30] From 1975 through 1993, 86 patients were reirradiated because their neurologic function had deteriorated or findings on imaging studies were consistent with progressive disease after an initial course of WBRT, or both. Neurologic symptoms were resolved in 27% of patients, 43% experienced a partial improvement, and 29% had either no change or their condition worsened after reirradiation. Imanaka et al used reirradiation therapy in three patients with recurrent brain metastases from SCLC.[31] The initial therapy varied among the three patients. Numerous retrospective studies have evaluated the effectiveness of stereotactic radiosurgery in the treatment of brain metastases. Sanghavi et al performed a retrospective review of 502 patients with brain metastases treated with radiosurgery and external beam radiation therapy at 10 institutions from January 1988 through May 1998.[33] Patients with brain metastases from any primary tumor treated with WBRT and a stereotactic radiosurgery boost to all visible lesions were included in this analysis. On multivariate analysis, performance status, controlled primary disease, and absence of extracranial metastases were significant predictors of improved survival. RTOG 9508 was a phase III trial comparing WBRT alone vs WBRT followed by stereotactic radiosurgery for patients with one to three unresected brain metastases ? 4 cm from any primary tumor except for leukemia or lymphoma.[35] Patients were not stratified according to histology. Patients treated with stereotactic radiosurgery were found to have a statistically significant improvement in the 1-year local control rate (82% vs 71%, P = .01).
The relatively discrete nature of brain metastases suits the physical dose parameters of brachytherapy. McDermott et al reported on the University of California, San Francisco, experience in 30 patients with a single brain metastasis who underwent temporary I-125 implantation.[ 38] One of the patients included in this study had SCLC. Most patients with non-small cell lung cancer (NSCLC) that has metastasized to the brain have a dire prognosis.
The findings were published this month in the Journal of Clinical Oncology and will be presented Monday, Oct. NSCLC accounts for 85% of all lung cancers, with 30%–50% of patients developing metastatic disease to the brain.
Treatment approaches include whole-brain radiation therapy, radiation for individual lesions, and surgery, typically for a single metastasis. There was, however, a small overall survival benefit seen in patients with refractory disease. Researchers believe that a therapeutic vaccine, belagenpumatucel-L, can increase long-term survival in patients with lung cancer.
Phase 2 clinical study has a sample of 75 patients, of whom 46 patients with stage IV cancer. NSCLC, non-small-cell lung carcinoma is a cancer of the lung epithelium relatively resistant to chemotherapy.


In stage IIIA oncologists recommend resection followed by chemotherapy and radiotherapy, and in stages IIIB and IV chemotherapy and radiation or palliative resection. It tends to disseminate earlier in the course of its natural history than non-small cell lung cancer and is clinically more aggressive. In contrast, two-thirds of patients with SCLC present with extensive-stage disease, with frank distant sites of involvement that cannot be incorporated into a safe and tolerable radiation portal.[4] In that regard, metastases from SCLC have a particular predilection for the brain.
Moreover, the severity of these symptoms may be a function of the degree of tumor-related vasogenic edema.
Imaging of the brain is very important in patients with SCLC who are suspected of having brain metastases, because these patients often have metabolic abnormalities or paraneoplastic syndromes that can produce symptoms that mimic those caused by intracranial metastases. These substances lead to the production of autoantibodies that crossreact with neuronal antigens and ultimately damage normal tissue.
Gaspar et al performed a recursive partitioning analysis of 18 pretreatment characteristics and three treatment-related variables in three consecutive Radiation Therapy Oncology Group (RTOG) brain metastases trials conducted between 1979 and 1993.[11] The analysis included 1,200 patients, over 50% of whom had NSCLC. This can be accomplished with the use of corticosteroids such as dexamethasone, which decreases the brain-to-tumor capillary permeability, thereby reducing edema of the brain.[6] Patients are typically prescribed dexamethasone (8 to 16 mg) divided into two to four daily doses.
In addition, many of the patients included in these studies were also treated with chemotherapy, either concurrently with radiation or shortly thereafter. However, the systemic treatment of patients with delayed presentation of brain metastases was individualized. Although these issues have not been addressed in a prospective fashion in the SCLC population alone, these patients were not specifically excluded from participation in these trials. The treatment options for these patients are often limited, and some authors have advocated repeat WBRT for palliation of symptoms. The most common primary sites were the breasts and lung, but the proportion of patients with SCLC was not identified. Two patients were treated with 30 Gy in 10 fractions to the whole brain, followed by a boost consisting of 10 Gy in four fractions for one patient and 9 Gy in three fractions for the other patient. They are also minimally invasive and displace normal brain parenchyma, which reduces the risk of injury to healthy tissue. These studies have suggested that radiosurgery improves both control of intracranial metastases and survival.[33] However, the survival benefit suggested by these studies may have been due to bias because patients with known favorable prognostic factors were selected.
Patients in this study were stratified according to their recursive partitioning analysis classification based on the RTOG's phase III brain metastases database reported by Gaspar et al (Table 1).[11] With this stratification system, current results can be compared with prior RTOG results. Furthermore, all subsets of patients treated with stereotactic radiosurgery were more likely to have a stable or improved performance status than those receiving WBRT alone. Another approach to LDR brachytherapy involves permanent interstitial implants in which iodine (I)-125 sources that are embedded in suture material are inserted or implanted directly into a tumor cavity. Of the 25 patients treated for recurrence of their metastasis, 4 received brachytherapy as a boost, and 1 had brachytherapy alone after resection without external irradiation.
But Yale researchers have identified a subset of those patients with a rare genetic mutation who are living significantly longer than patients without the mutation.
Since whole-brain radiation is associated with significant cognitive effects and the use of additional radiation therapy for progression is common in this population, the Yale researchers suspect that patients with the ALK mutation would benefit from radiation focused on individual metastases. The results of the study showed that patients had a mean survival of 14.5 months and survival at 5 years was 20%. Histologically, the most common variants are squamous non small cell, large cell cancer and adenocarcinoma. As already mentioned, treatment depends on disease stage, type of cancer, tumor extension and the health of the patient.
Approximately 10% of patients present with brain metastases at the time of initial diagnosis, and an additional 40% to 50% will develop brain metastases some time during the course of their disease.
One such disorder, Eaton-Lambert myasthenic syndrome, is seen in up to 3% of patients with SCLC and causes proximal muscle weakness, autonomic dysfunction, and paresthesias.
Antiepileptic medications such as phenytoin are not used routinely in this setting unless the patient presents with seizures.
As a result, few randomized trials have been conducted to guide the treatment evolution in this group of patients and to challenge the prevailing perspective that WBRT alone is the only effective treatment for brain metastases from SCLC. The radiation dose and fractionation schedules depended on the patient's performance and disease status and whether or not the patient had received previous prophylactic cranial irradiation (PCI). The median duration of the response was 10 months in patients with a complete response and 5 months in patients with a partial response. For those receiving accelerated hyperfractionation, the entire brain was treated with 1.6 Gy bid to a total dose of 32 Gy in 20 fractions. The median time interval between the first and second courses of irradiation was 7.6 months. In addition, the recursive partitioning analysis system attempts to remove the potential bias resulting from patient selection.


All other smaller brain metastases were treated using the Gamma Knife system, with a mean prescription dose of 21.3 Gy. The radiosurgery doses were based on a previous RTOG trial and depended on the size of the lesion.
There was no improvement in survival overall, but it did improve for recursive partitioning analysis class I patients, patients < 50 years of age, and patients with SCLC, any squamous cell cancers, or solitary brain metastases.
However, patients with the rare ALK mutation, which is found in just 5% of NSCLC cases, are living an average of four years, with the disease controlled in the brain nearly a year after their initial treatment, said the study’s lead author Dr.
The prognosis of patients with brain metastases from SCLC is poor despite years of research. The small number of patients with SCLC did not allow for this histology to be evaluated separately from other primaries.
The median survival of patients presenting with brain metastases was 7 months, compared with 3 months in patients with delayed development of metastatic disease. This trial confirmed a major finding from the previous retrospective studies-that a significant number of patients respond to WBRT, but the response duration and survival are short. The first two trials evaluated different accelerated fractionation regimens, including 40 Gy in 4 weeks, 40 Gy in 3 weeks, 30 Gy in 3 weeks, 30 Gy in 2 weeks, 10 Gy in one fraction, and 12 Gy in two fractions over 3 days.[27,28] The overall response to treatment was equivalent in all arms. The median dose of the first course of WBRT was 30 Gy, which was usually given in 10 fractions. Radiographic abnormalities consistent with radiation changes appeared in five patients, and one patient developed symptoms of dementia, which was attributed to radiation therapy.
Re-treatment consisted of 20 Gy and was administered to two patients with hyperfractionation (20 fractions) and to one patient with conventional fractionation (10 fractions).
New brain metastases detected on follow-up MRI scans were treated with repeat Gamma Knife radiosurgery. Therefore, the results of this study suggest that Gamma Knife radiosurgery appears to be as effective in treating brain metastases from SCLC as for those from NSCLC. The authors concluded that stereotactic radiosurgery can prolong survival in select patients with brain metastases only by 1 to 2 months.
The standard of care remains appropriate medical management followed by whole brain radiation therapy.
Based on this analysis, age, performance status, control of the primary tumor, and the presence or absence of extracranial metastatic disease were found to significantly influence survival. Patients who received radiation doses of more than 40 Gy had longer response durations than those given lower doses. However, 40% of patients who received shortcourse brain irradiation had evidence of extracranial progressive disease at the time of treatment, whereas all patients who received extended-course brain irradiation were in partial or complete remission outside the brain. Median survival was 4.5 months in both arms, with a 1-year overall survival rate of 19% in the accelerated fractionation arm and 16% in the accelerated hyperfractionation arm. From this review, the authors concluded that reirradiation should be offered to patients who develop progressive brain metastases. The median survival times were longer in this study for each recursive partitioning analysis class than they were in the RTOG studies.
Systemic disease remained the primary cause of death in more than two-thirds of the patients.
Current research is evaluating novel agents in an attempt to improve the survival and quality of life in these patients. The authors concluded that the irradiation schedules customarily used to treat brain metastases in SCLC are unlikely to eradicate intracranial tumors in the occasional patient whose systemic cancer has a durable complete response.
Given that higher radiation doses and altered fractionation schedules have not been shown to improve outcome in prospective trials, 30 Gy in 10 fractions continues to be one of the most commonly used fractionation schedules in WBRT. Therefore, this study suggested that radiosurgery may improve survival in all patients with brain metastases regardless of recursive partitioning analysis class.
The authors concluded that their experience with interstitial brachytherapy using I-125 implants was favorable and that interstitial brachytherapy is particularly useful in salvaging metastases that recur after prior therapies.
However, the most effective treatment for brain metastases from SCLC is the prevention of the development of clinically detectable disease. They suggested that it may be appropriate to consider treatment with doses greater that 40 Gy. For patients with a complete response to initial treatment, prophylactic cranial irradiation is an effective method of prevention. Therefore, the authors suggested that whole brain reirradiation is useful and safe for brain recurrence of SCLC.



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