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CLIN-NEURO-COGNITIVE NC-02. ASSESSING NEURO-COGNITIVE STATUS IN NEWLY PRESENTING PATIENTS WITH SUPRATENTORIAL INTRACRANIAL TUMOURS. Jennifer L. Scotland1, Ian R. Whittle1, and Ian J. Deary2; University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Dept. of Psychology, University of Edinburgh, Edinburgh, United Kingdom INTRODUCTION: Neurocognitive endpoints are increasingly included in clinical trials in neuro-oncological settings (Meyers & Brown, 2006). There is a need to identify short, repeatable measures of cognition that are sensitive to impairment in this group. Previous authors have proposed such batteries. METHODS: Newly presenting patients with a radiological diagnosis of any intracranial tumour (n 1⁄4 118) were assessed, prior to any surgical intervention, on a number of standardised cognitive and other measures as part of a larger study (Scotland et al., 2012). Their performance was compared with that of patients admitted for elective spinal surgery (n 1⁄4 85) and a healthy control group (n 1⁄4 80). RESULTS: Analysis of covariance compared the performance of the three groups. Age, sex, and National Adult Reading Test score (used to assess premorbid function) were the covariates. Patients with intracranial tumours performed significantly worse on the majority of the tests. The intracranial tumour cohort had significantly lower scores than did the spinal surgery and healthy control groups on the following measures: immediate and delayed memory (Rey Auditory Verbal Learning Test, RAVLT; p , 0.001); Trail Making Test Part B (p , 0.001); digit-symbol coding (p , 0.001); and verbal fluency (Controlled Oral Word Association Test, COWAT; p 1⁄4 0.002 and p , 0.001, respectively). There was a moderate-to-large effect size in the participant group for all tests. DISCUSSION/CONCLUSIONS: The RAVLT, Trail Making Test Part B, and COWAT are sensitive measures of cognitive impairment in patients with brain tumours and support Meyers & Brown’s (2006) proposal for the inclusion of these tests in clinical trials that have neurocognitive endpoints. The verbal fluency test, in particular, has a number of potential advantages for use in neuro-oncological settings, given that it can be completed by patients with focal motor deficits and is available in alternate forms to reduce practice effects. NC-03. A STANDARD NEUROLINGUISTIC APPROACH TO

BACKGROUND: WHO grade II low-grade gliomas (LGGs) with high risk factors for recurrence are mostly lethal despite current treatments, and novel approaches are needed. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in human leukocyte antigen (HLA)-A2+ adults with high-risk LGGs in the following three cohorts: 1) newly diagnosed patients without prior radiation therapy (RT); 2) newly diagnosed patients with prior RT, and 3) recurrent patients. METHODS: GAAs were interleukin-13 receptor (IL-13R)α2, EphA2, Wilms Tumor (WT)1, and Survivin, and synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for 8 courses with intramuscular injections of Toll-like receptor 3 agonist Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose (poly-ICLC), followed by q12-week booster vaccines. Primary endpoints were safety and CD8+ T-cell responses against vaccine-targeted GAAs. RESULTS: Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity has been encountered except for one case with Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 fever (Cohort 1). Enzyme-linked Immuno-SPOT (ELISPOT) assays demonstrated robust and sustained interferon (IFN)-γ responses against at least 3 of the 4 GAA epitopes in 10 and 4 cases of Cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFN-γ ELISPOT responses than Cohort 3 patients, suggesting newly diagnosed patients have superior vaccine-responsiveness to recurrent patients. IFN-γ ELISPOT response levels in this study is significantly higher than those observed in our previous phase I/II study in high-grade glioma patients (Okada et al. JCO 2011). Furthermore, IFN-γ ELISPOT response levels were significantly higher than those for IL-5, indicating effective type-1 skewing by the current regimen. Median progression-free survival (PFS) periods are 21 months (Cohort 1; since diagnosis; range 10-42) and 12 months (Cohort 3; since the 1st vaccine; range 3-26). The only patient with large astrocytoma in Cohort 2 has been progression-free for over 58 months since diagnosis. There was a positive trend between IFN-γ ELISPOT responses and progression-free survival (PFS) in Cohort 3 patients (P = 0.08 by The Cox proportional hazards model). CONCLUSIONS: The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade II LGG patients. These results suggest these patients may be suitable populations for vaccine therapy and warrant further evaluations of this approach. SECONDARY CATEGORY: Clinical Neuro-Oncology.

The level of serum neuron-specific enolase (NSE) has been implicated as a prognostic factor for patients with small cell lung cancer (SCLC). A prospective evaluation was undertaken to assess the prognostic significance of pretreatment NSE and treatment-induced minimum NSE values in patients with SCLC. Patients from two Phase III North Central Cancer Treatment Group trials [one for patients with extensive stage SCLC and one for patients with limited stage SCLC] were asked to enter this laboratory correlational trial. Both trials included treatment with four to six cycles of etoposide and cisplatin, and 121 patients (71 extensive stage SCLC and 50 limited stage SCLC) were entered into the present study of NSE. Pretreatment NSE values and treatment-induced minimum NSE values were independent predictors of time to progression and survival in multivariate analysis. Hazard rate modeling allowed the formulation of specific relationships of NSE to time to progression and survival. Pretreatment NSE levels inversely correlated with time to progression and survival in these patients with SCLC. Pretreatment NSE accounted for 28% of the variance in survival. Both pretreatment NSE and treatment-induced minimum NSE were independent prognostic predictors of time to progression and survival.

This analysis was performed to examine the outcome of adult and pediatric patients with brainstem tumors.Forty patients with brainstem glioma were evaluated retrospectively. Included were 24 females and 16 males ranging in age from 3 to 81 years (median, 29.5 years). These patients were treated with various combinations of surgery, chemotherapy, and radiotherapy (RT). The length of follow-up in survivors ranged from 0.6 to 20 years (median: 3.2 years, mean: 6 years). Survival rates were calculated with the Kaplan Meier method and differences between survival curves were calculated using the log-rank test.The overall 2 and 5-year survival rates were 44% and 34%, respectively. The median survival time was 19 months. The 5-year survival rate was 54% for patients with tumors outside the pons compared to 21% for those with tumors involving the pons (p = 0.04). The 5-year survival rate was 59% for patients with exophytic tumors as compared to 23% for those with intrinsic tumors (p = 0.05). Patients undergoing subtotal resection had a 5-year survival rate of 53% compared to 28% for those having only a biopsy or no surgical intervention (p = 0.04). None of the other potential prognostic or treatment related factors evaluated [patient age, tumor grade, tumor histology, radiotherapy parameters (including BID fractionation, 3-D treatment planning, or the use of doses55 Gy), or the administration of adjuvant chemotherapy] evaluated were associated with patient survival.Brainstem gliomas generally occur in younger individuals. The survival rates were better for patients with exophytic tumors, those involving sites other than the pons, and tumors amenable to subtotal resection. Improvements in the outcome of patients with brainstem gliomas will require new therapeutic approaches.

A three-arm Phase III randomized trial was performed to compare response rates, time to local or distant progression, and survival for patients with unresectable (Stage IIIA or IIIB) nonsmall cell lung carcinoma treated with standard fractionated thoracic radiotherapy (SFTRT) versus accelerated hyperfractionated thoracic radiotherapy (AHTRT) with or without combination etoposide and cisplatin chemotherapy.This trial was initiated in 1992 by the North Central Cancer Treatment Group. Patients with Stage IIIA or IIIB nonsmall cell lung carcinoma were eligible. They were randomly assigned to either SFTRT (6000 centigray [cGy] in 30 fractions) or AHTRT (150 cGy twice daily to a total dose of 6000 cGy, with a 2-week break after the initial 3000 cGy); the AHTRT was given alone or with concomitant cisplatin (30 mg/m2, Days 1-3 and 28-30) and etoposide (100 mg/m2, Days 1-3 and 28-30).A total of 110 patients were entered on study. Eleven patients were declared ineligible or off study on the day of study entry. This analysis was confined to the 99 eligible patients. This article reports mature follow-up, because more than 80% of the patients have died. The median follow-up of living patients was 2.5 years. There were suggestions of improvement in the rates of freedom from local recurrence and survival for patients treated with AHTRT (with or without chemotherapy) as opposed to SFTRT (P = 0.06 and P = 0.10, respectively). The improvement in survival associated with AHTRT (with or without chemotherapy) was statistically significant for the subgroup of patients with nonsquamous cell carcinoma after adjustment for other potentially confounding factors (P = 0.02). No differences in freedom from systemic progression or survival were found in a comparison of AHTRT with chemotherapy and AHTRT without chemotherapy.These results suggest that treatment of Stage IIIA or IIIB nonsmall cell lung carcinoma with AHTRT with or without chemotherapy may improve freedom from local progression and survival as compared with SFTRT, especially for patients with nonsquamous cell carcinoma. The statistical powers to detect the observed differences in median time to local progression and survival were approximately 55% and 35%, respectively. Therefore, further investigation comparing SFTRT with AHTRT is warranted.

An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung. The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small. We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma.Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated. Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths. The actuarial risk of second cancers was estimated by the Kaplan-Meier method.Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold. Second lung cancer risk was increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21). Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking.Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention.

Previous nonsmall cell lung carcinoma studies have shown that patients with ipsilateral mediastinal (N2) lymph node involvement who underwent surgical resection have a greater local recurrence rate than those with less lymph node involvement (N0, N1). Therefore, it was hypothesized that complete surgical clearance of subclinical lymph node disease is difficult in N2 patients and that adjuvant postoperative thoracic radiotherapy (TRT) may be beneficial.A retrospective review was performed to determine the local recurrence and survival rates for patients with N2 disease undergoing complete surgical resection with or without adjuvant TRT. Between 1987 and 1993 at the Mayo Clinic, 224 patients underwent complete resection of N2 nonsmall cell lung carcinoma. More than one mediastinal lymph node station was sampled in 98% of patients; 39% then received adjuvant TRT (median dose, 50.4 grays).The median follow-up time was 3.5 years for the patients who were alive at the time of the analysis. The surgery alone versus surgery plus TRT groups were well balanced with respect to gender, age, histology, tumor grade, number of mediastinal lymph node stations dissected or involved, and involved N1 lymph node number. There were slightly more patients with right lower lobe lesions (compared with other lobes), patients with multiple lobe involvement, and patients with only one N2 lymph node involved in the surgery alone group. After treatment with surgery alone, the actuarial 4-year local recurrence rate was 60%, compared with 17% for treatment with adjuvant TRT (P0.0001). The actuarial 4-year survival rate was 22% for treatment with surgery alone, compared with 43% for treatment with adjuvant TRT (P = 0.005). On multivariate analysis, the addition of TRT (P = 0.0001), absence of superior mediastinal lymph node involvement (P = 0.005), and fewer N1 lymph nodes involved (P = 0.02) were independently associated with improved survival rate.This study, which to the authors' knowledge is the largest evaluating adjuvant TRT in N2 nonsmall cell lung carcinoma, suggests that adjuvant TRT may improve local control and survival.

To try and identify biologic differences based on tumor grade and histologic type between the major classes of glial tumors, including low-grade diffuse fibrillary and pilocytic astrocytomas, oligodendrogliomas, and mixed oligo-astrocytomas and high-grade diffuse fibrillary astrocytomas, oligodendrogliomas and mixed oligo-astrocytomas.Utilizing the St. Anne-Mayo (SAM) grading system, the incidence, patient characteristics, and survivals of 196 patients with low-grade (SAM grade 1 + 2) and 318 patients with high-grade (SAM 3 + 4) supratentorial tumors were compared.Among low-grade tumors, most favorable were 5- and 10-year survival rates for patients with pilocytic astrocytomas, which were 85% and 79%, respectively. Median survival and 5- and 10-year survival rates for the other low-grade tumors were lower, and were proportionately improved by the presence of an oligodendroglial component: diffuse fibrillary astrocytomas-4.7 years, 46%, and 17%, oligodendroglioma-9.8 years, 73%, and 49%; and mixed oligo-astrocytoma-7.1 years, 63%, and 33%, respectively. For high-grade tumors, patients with either oligodendrogliomas or mixed oligo-astrocytomas had comparable favorable survivals in comparison to diffuse fibrillary astrocytomas. Median survivals and 5- and 10-year survival rates were 4.5 years, 45%, and 15% for the oligodendrogliomas and mixed oligo-astrocytomas versus 0.8 years, 3%, and 0% for the diffuse fibrillary astrocytomas, respectively.These survival data suggest that both low-grade and high-grade supratentorial gliomas have outcomes which are highly dependent upon histologic type.

We performed genetic analysis on 12 second primary non-small cell lung cancers in patients surviving small cell lung cancer to assess the potential contribution of smoking to the development of these tumors. Mutations of TP53 were found in three (25%) tumors, KRAS2 in three (25%) tumors, and CDKN2 in two (18%) tumors. Four (50%) mutations (one each in TP53 and CDKN2 and two in KRAS2) were G:C to T:A transversions on the coding strand, a mutation accounting for approximately one-third of mutations in smoking-related tumors but uncommonly found in lung cancers not associated with smoking. The genetic changes in these second lung cancers are more representative of smoking-associated malignancies than lung cancers arising in patients occupationally exposed to irradiation and atomic bomb survivors.

The supratentorial low-grade gliomas are a heterogeneous group of central nervous system tumours. Knowledge of their biology, primarily based on histologic subtype and patient age, is helpful in determining prognosis and guiding therapeutic recommendations. The pilocytic tumours usually occur in younger patients and carry a favourable prognosis. Recurrence following gross total excision is rare, and approximately 80% of patients undergoing subtotal removal with or without postoperative radiation therapy (RT) will survive 10 years or longer. In contrast, non-pilocytic, supratentorial low-grade tumours (including the diffuse fibrillary, protoplasmic and gemistocytic subtypes), as well as mixed oligoastrocytomas and oligodendrogliomas are infrequently cured, even with gross total excision. Survival benefit with postoperative RT has been suggested by several retrospective studies. When RT is prescribed, localized treatment fields are suggested for total doses of 4500 to 6500 cGy. Ongoing prospective, randomized studies hopefully will clarify the role of RT in these neoplasms, as well as the optimal dose.

A Phase I/II study of an aggressive six-drug chemotherapy regimen followed by the use of sequential hemibody radiation therapy as a possible non-cross-resistant systemic treatment was undertaken for patients with extensive stage small cell lung cancer.The 20 enrolled patients received 7 cycles of cyclophosphamide-based chemotherapy. The first cycle consisted of cyclophosphamide, doxorubicin, etoposide, vincristine, and lomustine. Subsequent cycles used a regimen of doxorubicin alternating with cisplatin. Thoracic radiation was delivered in a split-course fashion during the first week of chemotherapy cycles 5 and 6 (2000 cGy in five fractions during each week). Prophylactic cranial radiation was delivered in a split-course fashion during the first week of chemotherapy cycles 2 and 3 (1700 cGy in 5 fractions during each week). After the 7 cycles, patients received 600 cGy upper hemibody radiation followed by 800 cGy lower hemibody radiation.Nineteen of 20 patients were evaluable for toxicity and response to treatment. Hematologic toxicity accounted for treatment delays or decreased doses in 16 of 19 patients. Thirteen patients completed the initial 7 cycles; progressive disease was the only reason for discontinuing treatment. Two patients had fatal hematologic complications after lower hemibody radiation. Three patients had severe or greater peripheral neurologic toxicity, two had severe central neurologic toxicity, and one had severe cardiac toxicity. Of 19 patients, 9 achieved a complete response; median survival was 11.5 months. Five-year progression free survival and 5-year overall survival were 27% and 16%, respectively.This aggressive regimen is feasible for patients with extensive stage small cell lung cancer; however, hematologic-related mortality after lower hemibody radiation suggests that future investigations should be initiated at lower initial doses of lower hemibody radiation. Long term survival of the patients suggests that sequential hemibody radiation treatment warrants further investigation.

Lung cancer during pregnancy is rare. Herein we describe a case of metastatic cancer of the lung in a 36-year-old pregnant patient whose initial complaint was pain in the left thigh. Management of this neoplasm during pregnancy depends on the gestational age of the fetus and the potential operability of the tumor. Surgical, chemotherapeutic, and radiation management considerations are discussed.

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.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.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.Prophylactic cranial irradiation may contribute to improved survival in patients with LSSCLC who achieve a complete response after chemotherapy and thoracic radiation therapy.

To assess the role of clinical factors, size of lesion, site of involvement, and radiation dose in patients with cerebral arteriovenous malformations (AVMs) who underwent stereotactic radiosurgical treatment.We reviewed the results in 121 patients with cerebral AVMs treated with the Leksell "Gamma Knife" between January 1990 and December 1993 at the Mayo Clinic in Rochester, Minnesota.The following strict dose-volume protocol was used: AVMs 2.0 cm or smaller in diameter (volume, 4.2 cm3 or less) received 20 Gy to the margin of the nidus, those between 2.1 and 3.0 cm in diameter (4.3 to 14.1 cm3) received 18 Gy to the margin, and those that exceeded 3.0 cm in diameter (more than 14.1 cm3) received 16 Gy to the margin. Lesions that involved the brain stem received a radiosurgical dose of 18 Gy or less to the margin. Patients participated in regular follow-up clinical and imaging studies for up to 55 months.Follow-up cerebral angiography in 43 patients demonstrated total obliteration of the AVM nidus in 31 (72.1%), including 5 of 7 (71.4%) who had AVMs with a volume larger than 10 cm3. Clinical follow-up revealed that 111 patients (91.7%) had a stable or improved outcome, 3 had a nonfatal AVM hemorrhage, 2 suffered a fatal hemorrhage, and 2 died of causes not directly attributed to the AVM or radiosurgical treatment. Two patients had new or increased, nondisabling neurologic deficits as a result of treatment, and one patient had a temporary partial eyelid ptosis.Our findings suggest that previous theories about the relationship between AVM size and rate of obliteration after radiosurgical treatment may need revision. Our experience confirms that radiosurgical treatment for cerebral AVMs is safe and effective, even in cases for which the latency period before obliteration is longer than 2 years.

From the preceding supporting evidence, the following conclusions can be drawn: Supratentorial LGGs are a pathologically diverse group of CNS neoplasms whose natural history is primarily dependent upon histologic subtypes. The observed survival of all histologic subtypes of supratentorial LGGs are statistically significantly worse than that of an age- and sex-matched control population. Moderate-dose postoperative RT appears to improve survival in, and may cure, a subset of patients with supratentorial nonpilocytic LGG, particularly in those in their 30s and older. Multiple shaped localized treatment fields should be utilized because whole brain radiation is both unnecessary and associated with greater toxicity. Patients with supratentorial LGGs are usually neurologically "intact" but do exhibit cognitive impairment. Neurologic, functional, cognitive, and affective status do not appear to be negatively impacted by modern postoperative RT in adults with supratentorial LGG. Therefore, all adult patients with histologically verified supratentorial low-grade nonpilocystic astrocytomas (diffuse fibrillary astrocytoma, mixed oligo-astrocytoma, or oligodendroglioma) should routinely receive postoperative RT. Localized treatment fields should be employed. The optimum dose of radiation within the range of 4,500 to 6,480 cGy has yet to be determined.

Patients with esophageal cancer and a malignant tracheoesophageal fistula (TEF) have an extremely poor prognosis. Additionally, these patients often are denied treatment with radiation therapy because there is concern that these treatments may increase the size and associated problems of the TEF.To determine the appropriate treatment (use of radiation therapy) for patients with esophageal cancer and malignant TEF, a review was performed of all such cases seen at the Mayo Clinic between 1971 and 1991.Between 1971 and 1991, 41 patients with malignant TEF arising as a result of esophageal cancer were seen at the Mayo Clinic in Rochester. Twenty-eight of these cancers were locally recurrent, and this group of patients had a uniformly poor outcome (median survival time, 1.4 months). Thirteen patients had a malignant TEF and had not received previous treatment for their esophageal cancer. The median survival length was 4 months for this group of patients. Of the 41 patients in this study, 10 received radiation therapy for their malignant TEF (30-66 Gy). The median survival length of this group of patients was 4.8 months. Six of these 10 patients died of metastatic disease (median survival length, 9 months), and there was no evidence of progression of the local tumor. Four of these 10 patients died of local progression of the malignancy (median survival length, 3 months).Radiation therapy did not increase the severity of the TEF. The authors conclude that radiation therapy can be administered safely in patients with TEF resulting from esophageal cancer. In some patients, radiation treatment may contribute to stabilization of the local tumor process (60% of patients treated with radiation therapy died of metastatic disease without local progression of tumor); however, all patients in this study eventually died of esophageal cancer.

Supratentorial pilocytic astrocytomas are uncommon tumors, the prognosis and management of which have been controversial.The authors retrospectively studied the clinical and pathologic aspects of 51 patients with supratentorial pilocytic astrocytomas, with particular reference to their response to treatment.The study group consisted of 25 male and 26 female patients (median age, 15 years). The extent of surgical removal was gross total or radical subtotal in 16 patients and subtotal removal or biopsy in 35. At a median follow-up of 14.9 years, 41 patients were alive. Overall survival was 82% at 10 and 20 years; 89% of surviving patients were fully active. Survival at 10 years was 100% for the 16 patients who underwent gross total or radical subtotal removal and 74% for the 35 who had subtotal tumor removal or biopsy. No association was found between pathologic features such as histologic grade or flow cytometric characteristics and patient survival.Supratentorial pilocytic astrocytomas behave differently from low-grade astrocytomas of the diffuse or fibrillary type in that they have a favorable prognosis. Radiation therapy appears not to be needed for patients undergoing gross total removal. In patients undergoing subtotal resection, close follow-up with additional surgery or radiation therapy at the time of tumor progression is recommended. Patients who have biopsy only should receive radiation therapy. Histologic grading and flow cytometric analysis add little to clinical decision making with regard to patients with pilocytic astrocytoma.

The majority of patients with astrocytomas of the cerebellum have an excellent prognosis; however, a small percentage of patients continue to do poorly. To clarify the clinical, pathologic, and treatment characteristics that determine prognosis and therapeutic recommendations, a large group of patients with astrocytic tumors of the cerebellum was reviewed and analyzed.A clinicopathologic analysis was performed of all patients undergoing initial operation for astrocytomas in the cerebellum between 1960 and 1984. Of the 132 patients, 105 patients had pilocytic astrocytomas and 27 had diffuse astrocytomas.Multivariate analysis revealed that the division of pilocytic and diffuse histologic type was the most significant prognostic factor influencing survival. The 5-year, 10-year, and 20-year survival rates were 85%, 81%, and 79%, respectively, for patients with pilocytic astrocytomas and 7%, 7%, and 7%, respectively, for patients with diffuse astrocytomas (P0.001). Pilocytic astrocytomas occurred in a younger age group and were more commonly cystic and completely resected.Astrocytomas of the cerebellum can be divided into two principal groups, the pilocytic and the diffuse astrocytomas, each of which has distinct clinical, pathologic, and prognostic characteristics.

The primary goal of this study was to determine the incidence of severe or greater acute radiation toxicity, and secondarily, response, survival, and local control in patients with unresectable Stage IIIA or B non-small cell lung cancer treated with accelerated hyperfractionated thoracic radiation therapy (AHTRT).From September, 1989 through March, 1990, 21 evaluable patients with unresectable Stage IIIA or B non-small cell lung cancer were treated with AHTRT, using 6000 cGy in 40 fractions of 150 cGy twice daily, 6 hours between fractions, with a 2-week break midway through treatment.Two patients (9.5%) had acute Grade 3 radiation esophagitis requiring intravenous hydration, and two patients (9.5%) had acute Grade 3 radiation pneumonitis requiring oxygen and steroids. Only one patient had chronic toxicity, a Grade 3 radiation pneumonitis. Five patients (24%) achieved a complete response, whereas eight (38%) had a partial response or regression. With minimum follow-up of nearly 3 years, 3 patients are alive and 18 are dead. The median survival time and 1-, 2-, and 3-year survival rates were 10.8 months, 48%, 29%, and 14%, respectively. Local control was achieved in 11 of 21 (52%) patients.This AHTRT regimen can be given with an acceptable incidence of acute radiation toxicity. Response, survival, and local control rates in this unfavorable group of patients are encouraging. A North Central Cancer Treatment Group Phase III study of standard thoracic radiation therapy (6000 cGy in 30 fractions of 200 cGy daily) versus AHTRT (+/- chemotherapy) is now open.

Medulloblastoma, the most common embryonal tumor of the central nervous system, affects both children and adults. It poses a significant therapeutic challenge in that age-dependent differences exist, not only in their pathobiology, but in the efficacy of chemotherapy and radiotherapy. This is particularly the case in very young children, whose still developing nervous system exhibits a low tolerance to radiotherapy. We review the epidemiology, clinical presentation, radiologic features, and current therapeutic concepts relative to this unique neoplasm. Efforts are made to highlight clinical controversies.

After latent periods lasting from 7 to 23 years, sarcomas of the calvaria developed in four patients who had received radiation therapy for a brain tumor. There was no evidence of bony disease before radiation therapy, and the sarcoma (two fibrosarcomas and two osteosarcomas) developed in the field of radiation in all four patients. One of these four died during resection of the tumor, two survived for either 7 or 21 months after diagnosis of the sarcoma, and one was alive at 23 months after the clinical appearance of the sarcoma. The latter patient has had two resections and extensive chemotherapy. Distant metastases were not present in any of the patients. Sarcoma of the calvarial bones is a serious but rare remote effect of radiation therapy for brain tumors.

Archean rocks form the eastern margin of the 1.1 Ga old Central North American rift along the eastern shore of Lake Superior and have been tilted westwards in response to rifting. Paleomagnetic and structural data from 2.6 Ga old Matachewan dykes suggest a westward crustal tilt of about 60°, which agrees well with dips recorded in nearby Keweenawan volcanics that rest directly on basement rocks. The Matachewan dyke swarm occurs throughout the east shore region of Lake Superior, whereas Keweenawan supracrustal sequences, which give a more precise estimate of tilt, are restricted to a few isolated shoreline patches. Estimates of crustal tilt can be obtained from the dykes on a regional basis, thus generating a more complete picture of basement deformation adjacent to a major intracratonic rift.

A total of 211 patients with limited small cell lung cancer were assessed retrospectively for long-term toxicities, treatment-related deaths, and second primaries. All had received treatment with various combinations of doxorubicin, vincristine, cisplatin, lomustine, cyclophosphamide, and etoposide with or without split-course thoracic radiotherapy (4,000 cGy/10 fractions) and/or split-course prophylactic cranial irradiation (3,600 cGy/10 fractions). Sixty-eight (32%) of the patients survived longer than 1.5 years and formed the basis of this study. Debilitating pulmonary, cardiac, and neurologic toxicity was noted in 12%, 14%, and 15%, respectively, of long-term survivors. These complications were the result of aggressive combined modality therapy. Certain drugs appeared to cause additive toxicity when combined with radiation. Three patients developed new primary tumors of squamous cell origin. Attention must be directed to defining the safest way to employ aggressive combined modality treatment for these patients.

Summary 1. An application of the Berthelot reaction to the analysis of microgram quantities of ammonium in urine has been described in terms of a newly developed reagent system incorporating ferrocyanide as a catalyst, and the procedure has been adapted for the AutoAnalyzer. 2. Criteria of sensitivity of the reaction conditions, studies on dialysis conditions, analytical recoveries and the contributions of urea and creatinine as ammonogenic substances under the reaction conditions are presented.

This paper deals with simple or traumatic tenosynovitis as distinct from pyogenic or granulo matous affections of the tendon sheaths. Literature on the subject in this country is scanty, and lacking in a clear understanding of the under lying pathology, for although in the pyogenic group a true infection of the tendon sheath is present, this is not always so in simple tenosynovitis, and it is unfortunate that the nomenclature of each should remain the same. Although true teno synovitis may occur in other regions, the one most commonly affected in simple " tenosynovitis " is the dorsum of the forearm proximal to the wrist joint. Standard works on surgery continue to refer to it as " tenosynovitis", but as the lesion responsible is well above the upper limit of the tendon sheaths themselves, we would prefer the name " peritendi nitis crepitans " as being more truly descriptive. Tenosynovitis is a well known cause of industrial disability, but, except in the mining community, its occupational significance has never been fully appreciated. In certain circumstances, its incidence may be high as during the war years when many people, recruited for work in factories for the first time, were engaged in unaccustomed tasks involving speed and intensity of effort (Reed and Harcourt, 1943 ; Blood, 1942). Tenosynvotis, however, is by no means confined to factory workers. It has been reported among agricultural workers and others (Pozner, 1942 ; Flowerdew and Bode, 1942 ; Taylor-Jones, 1942). The present study is concerned mainly with the condition as it affects the wrist and forearm of the manual worker in industry (peritendinitis crepitans), but an additional series of true tenosynovitis cases involving tendon sheaths in other situations is also considered. If it is not diagnosed and treated promptly, tenosynovitis can cause much needless absenteeism and continuing disability, and at one factory (Vauxhall Motors) employing 12,000 persons medical records in the past show that about 40 cases occur annually, with an average absence of 21 days.

1. In this series of posterior onlay grafting with fresh autogenous bone and without internal fixation, in the treatment of non-infective structural lesions in the lumbo-sacral area, 71 per cent of the patients were relieved of their symptoms, but bony fusion was obtained in only 60 per cent. 2. It is probable that with this technique twelve weeks' immobilisation in a plaster bed is required. 3. Some failures are ascribed to the use of an insufficient quantity of bone or to poor apposition of the graft to its bed. 4. It is evident that the more vertebrae one attempts to fuse the more difficult it is to succeed. When the diseased area is successfully fused but an unnecessarily long graft has been used, a pseudarthrosis above the level of the pre-operative pathology may be the cause of persisting backache. For these reasons we believe that one should not attempt to graft more vertebrae than is necessary to stabilise the local lesion. 5. The complication rate, particularly from deep vein thrombosis, was high. This major complication could perhaps be overcome by using banked bone. 6. The indications for the operation are assessed as follows. It should be done for low back pain only when there is a definite diagnosis and a limited extent of structural pathology; one can then expect excellent results when successful fusion is achieved and also an appreciably high proportion of satisfied patients even when bony fusion has not been obtained, presumably because there is a fibrous union strong enough to stabilise the affected spine. It is inadvisable to undertake lumbar-lumbo-sacral fusion for intervertebral disc degeneration when there are more than three adjacent vertebrae involved, and in any case operation should be confined to the indicated extent.

In the setting of a large or irregularly shaped tumor, adjacent or intentionally overlapped intraoperative electron fields may be required to give adequate coverage of the intraoperative target volume. The matching of such intraoperative electron fields present special dosimetric problems because of the divergence of electron isodose curves with depth. In the intraoperative setting, where large, single-fraction doses are delivered, the low- and high dose areas which result from gaps or overlaps between the diverging isodose curves of electron fields matched at depth or the surface may translate into decreased local tumor control or excessive normal tissue toxicity. This study examines the dosimetry of gapped, adjacent, and overlapped 8 X 9 cm2 rectangular intraoperative fields, for 9 to 18 MeV electrons, using film densitometry. "Ideal" methods of matching rectangular intraoperative electron fields are presented, and include: 1) a 2-mm gap plus surface bolus for adjacent fields, and 2) placing a tenth-value layer shaped lead cutout in the overlap region for intentionally overlapped fields.

Forty-four cases of meningeal hemangiopericytoma that were treated between 1938 and 1987 are reviewed. Fifty-five percent of these tumors occurred in men. The average age of the patients at diagnosis was 42 years. The average duration of preoperative symptoms was 11 months. Symptoms were related to tumor location, which was similar to that of meningioma. The operative mortality was 9% overall, and has been zero since 1974 (18 patients). The average time before the first recurrence was 47 months, with the recurrence rates at 1, 5, and 10 years after surgery being 15, 65, and 76%, respectively. Ten patients have developed extraneural metastasis, mostly to lung and bone, at an average of 99 months after the first operation. The 10- and 15-year rates of metastasis were 33 and 64%, respectively. The average survival period has been 84 months, with survival rates at 5, 10, and 15 years after surgery of 67, 40, and 23%, respectively. The histological diagnosis of the tumor was not related to survival or recurrence and did not change with recurrence. Tentorial and posterior fossa tumors tended to be more lethal. Total tumor resection favorably affected recurrence and survival, as opposed to subtotal resection. Metastasis adversely affected survival, and was followed by death at an average of 24 months after its diagnosis. Radiation therapy after the first operation extended the average time before first recurrence from 34 to 75 months, and extended survival from 62 to 92 months.