Estimation of tumor control probability model parameters from 3-D dose distributions of non-small cell lung cancer patients.

Tumor control probability (TCP) model calculations may be used in a relative manner to evaluate and optimize three-dimensional (3-D) treatment plans. Using a mathematical model which makes a number of simplistic assumptions, TCPs can be estimated from a 3-D dose distribution of the tumor given the dose required for a 50% probability of tumor control (D50) and the normalized slope (gamma) of the sigmoid-shaped dose-response curve at D50. The purpose of this work was to derive D50 and gamma from our clinical experience using 3-D treatment planning to treat non-small cell lung cancer (NSCLC) patients. Our results suggest that for NSCLC patients, the dose to achieve significant probability of tumor control may be large (on the order of 84 Gy) for longer (> 30 months) local progression-free survival.

Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer.

PURPOSE: A phase II study was conducted by the Southwest Oncology Group (SWOG) to assess the efficacy and toxicity of concurrent carboplatin, etoposide, and thoracic radiation (XRT) in a defined population of poor-risk patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage III NSCLC were eligible if they were excluded from cisplatin-based protocols because of poor pulmonary or renal function, history of congestive heart failure, hearing loss, peripheral neuropathy, or weight loss. Carboplatin 200 mg/m2 daily intravenously days 1, 3, 29, and 31 and etoposide 50 mg/m2 daily intravenously days 1 through 4 and 29 through 32 were administered. Beginning day 1, XRT was delivered at 1.8 to 2.0 Gy daily to a total dose of 61 Gy. RESULTS: Within a period of 1 year, 63 patients were registered and 60 were eligible. Patient characteristics were age 47 to 79 years, performance status 0 to 1 (82%) and 2 (18%), and stages IIIA (60%) and IIIB (40%) NSCLC. The most common grades 3 and 4 toxicities included leukopenia (50%), thrombocytopenia (23%), and esophagitis (15%). There were no treatment-related deaths. The overall confirmed response rate was 29%, and median overall survival was 13 months (95% confidence interval, 11 to 14 months). The 2-year survival rate was 21%. CONCLUSION: This chemoradiotherapy regimen is well tolerated in poor-risk patients and yields a median survival similar to that of good-risk patients who received cisplatin-based chemoradiotherapy. This chemoradiotherapy regimen will be compared with XRT alone in poor-risk patients with stage III NSCLC in a randomized phase III trial.

Volume and dose parameters for survival of non-small cell lung cancer patients.

BACKGROUND AND PURPOSE: To determine the effect of tumor volume and dose factors derived from 3-D treatment planning dose distributions on survival outcome for non-small cell lung cancer patients. MATERIALS AND METHODS: Seventy-six consecutive patients diagnosed with medically inoperable or locally advanced, unresectable non-small cell lung cancer planned with 3-D treatment planning between 1986 and 1992 were the subject of this retrospective study. Patient characteristics and dosimetric parameters were analyzed for influence on overall survival and local progression-free survival (LPFS) using univariate and multivariate analysis. RESULTS: Nodal stage and stage were the most significant factors for overall survival and LPFS duration on both univariate and multivariate analysis. We found a wide range of primary tumor volume sizes for each stage. Patients with tumor volumes <200 cm3 had longer survival (P = 0.047). In an analysis stratifying patients into four groups by tumor volume (<200 cm3 versus >200 cm3) and nodes (negative versus positive), patients in the group with no nodal disease and <200 cm3 tumor volumes survived longer than patients in any other group (P = 0.046). No dose factors were statistically significant for longer survival. Longer LPFS was seen for (a) isocenter dose >70 Gy (P = 0.055) for the overall group of patients, (b) within a subgroup with no nodal disease and >73 Gy (P = 0.054), and (c) within a subgroup with no nodal disease and tumor volume <200 cm3 receiving >73 Gy (P = 0.086). CONCLUSIONS: Several findings from the volume and dosimetric analysis in this study are noteworthy. Stage was found to be a poor predictor of primary tumor volume size. Also, tumor volume size (<200 cm3) in conjunction with nodal status (negative nodes) had an impact on survival though there was a mix of stage (I, IIIa, IIIb) in this group of patients. Finally, dose appears to influence local control (LPFS) for the overall group of patients and when tumor volumes are <200 cm3. Our data indicate that outcome following radiation may be better predicted by a staging system that takes into account tumor volume and nodal spread rather than a system that is largely based on anatomic location of disease. Dose prescription for lung cancer treatment might better be written based on tumor volume size.

Dose-volume complication analysis for visual pathway structures of patients with advanced paranasal sinus tumors.

PURPOSE: The purpose of the present work was to relate dose and volume information to complication data for visual pathway structures in patients with advanced paranasal sinus tumors. METHODS AND MATERIALS: Three-dimensional (3D) dose distributions for chiasm, optic nerve, and retina were calculated and analyzed for 20 patients with advanced paranasal sinus malignant tumors. 3D treatment planning with beam's eye view capability was used to design beam and block arrangements, striving to spare the contralateral orbit (to lessen the chance of unilateral blindness) and frequently the ipsilateral orbit (to help prevent bilateral blindness). Point doses, dose-volume histogram analysis, and normal tissue complication probability (NTCP) calculations were performed. Published tolerance doses that indicate significant risk of complications were used as guidelines for analysis of the 3D dose distributions. RESULTS: Point doses, percent volume exceeding a specified published tolerance dose, and NTCP calculations are given in detail for patients with complications versus patients without complications. Two optic nerves receiving maximum doses below the published tolerance dose sustained damage (mild vision loss). Three patients (of 13) without optic nerve sparing and/or chiasm sparing had moderate or severe vision loss. Complication data, including individual patient analysis to estimate overall risk for loss of vision, are given. CONCLUSION: 3D treatment planning techniques were used successfully to provide bilateral sparing of the globe for most patients. It was more difficult to spare the optic nerves, especially on the ipsilateral side, when prescription dose exceeded the normal tissue tolerance doses. NTCP calculations may be useful in assessing complication risk better than point dose tolerance criteria for the chiasm, optic nerve, and retina. It is important to assess the overall risk of blindness for the patient in addition to the risk for individual visual pathway structures.

Dose escalation for non-small cell lung cancer using conformal radiation therapy.

PURPOSE: Improved local control of non-small cell lung cancer (NSCLC) may be possible with an increased dose of radiation. Three-dimensional radiation treatment planning (3D RTP) was used to design a radiation therapy (RT) dose escalation trial, where the dose was determined by (a) the effective volume of normal lung irradiated, and (b) the estimated risk of a complication. Preliminary results of this trial were reviewed. METHODS AND MATERIALS: A graph of the iso-normal tissue complication probability (NTCP) levels associated with a dose and effective volume (V(eff)) was derived, using normal tissue parameters derived from the literature. This led to a dose escalation schema, where patients were sorted into 1 of 5 treatment bins, determined by the V(eff) of the best possible treatment plan. The starting doses ranged from 63 to 84 Gy. Each treatment bin was then escalated separately, as in Phase I dose escalation fashion, with Grade > or = 3 radiation pneumonitis defined as dose limiting. To allow for dose escalation, we required patient follow-up to be > or = 6 months for at least three patients. 3D treatment planning was used to irradiate only the radiographically abnormal areas, with 2.1 Gy (corrected for lung inhomogeneity)/day. Clinically uninvolved lymph nodes were not treated prophylactically. RESULTS: A total of 48 NSCLC patients have been treated (Stage I/II: 18 patients; Stage III: 28 patients; mediastinal recurrence postsurgery: 2 patients). No radiation pneumonitis has been observed in the 30 patients currently evaluable beyond the 6-month time point. All treatment bins have been escalated at least once. Current doses in the five treatment bins are 69.3, 69.3, 75.6, 84, and 92.4 Gy. None of the 15 evaluable patients in any bin with > or = 30% NTCP experienced clinical radiation pneumonitis, implying that the actual risk is < 20% (beta error rate 5%). Despite the observation of the clinically negative lymph nodes at high risk, there has been no failure in the untreated mediastinum as the sole site of first failure. Three of 10 patients receiving > or = 84 Gy have had biopsy proven residual or locally recurrent disease. CONCLUSION: Successful dose escalation in a volume-dependent organ can be performed using this technique. By incorporating the effective volume of irradiated tissue, some patients have been treated to a total dose of radiation over 50% higher than traditional doses. The literature-derived parameters appear to overestimate pneumonitis risk with higher volumes. There has been no obvious negative effect due to exclusion of elective lymph node radiation. When completed, this trial will have determined the maximum tolerable dose of RT as a single agent for NSCLC and the appropriate dose for Phase II investigation.

Chemotherapy followed by accelerated fractionated radiation for larynx preservation in patients with advanced laryngeal cancer.

PURPOSE: Larynx preservation in advanced, resectable laryngeal cancer may be achieved using induction chemotherapy (CT) followed in responding patients by definitive radiation (RT). To address potential accelerated repopulation of clonogenic tumor cells during the prolonged total treatment time, we studied the feasibility of accelerated fractionated RT after CT. METHODS: Patients with advanced laryngeal cancer received two cycles of cisplatin 100 mg/m2 and fluorouracil (5-Fu) 1,000 mg/m2/d for 5 days. Responding patients received a third cycle after which those who had complete response or tumor down-staging to T1 proceeded with accelerated RT: 70.4 Gy delivered over 5.5 weeks. Patients who achieved a lesser response to CT underwent total laryngectomy and postoperative RT. RESULTS: Thirty-three patients were accrued. Three died during the course of CT and two declined definitive treatment after CT. Twenty-one patients had a major response to CT, 20 of whom received accelerated RT. Median weight loss during RT was 11%. Late severe morbidity was observed in five patients (25%). All four patients who underwent salvage laryngectomy after accelerated RT experienced major postoperative complications. The locoregional failure rate was 25%. The larynx was preserved in 48% of the total study population and in 80% of the patients irradiated according to the study protocol. CONCLUSION: Accelerated RT after CT as delivered in this study may increase both acute and long-term morbidity rates compared with studies using standard RT after CT. It did not seem to improve local/regional tumor control or survival despite stringent patient selection criteria.

Role of recombinant interferon alfa-2a maintenance in patients with limited-stage small-cell lung cancer responding to concurrent chemoradiation: a Southwest Oncology Group study.

PURPOSE: This study was designed to determine if recombinant interferon alfa-2a (rIFN alpha-2a) could prolong remission duration and/or survival in patients with limited-stage small-cell lung cancer (SCLC) who achieved an objective response to chemoradiotherapy. A secondary end point was to assess the toxicity of chronic IFN administration. PATIENTS AND METHODS: One hundred seventy-one of 215 eligible patients achieved an objective response and were eligible to receive rIFN alpha-2a (3 million units [MU]/m2 subcutaneously three times per week escalated to 9 MU/m2 as tolerated) or observation for 2 years. RESULTS: One hundred thirty-two of 140 registered patients were eligible. Sixty-four patients were randomized to receive IFN and 68 to observation alone. The median time from randomization to progression was 9 months on the IFN arm and 10 months on the observation arm (P = .72). The overall median survival time was 16 months on the observation arm versus 13 months on the IFN arm (P = .77). Significant toxicities occurred in the rIFN alpha-2a arm. Grade 3 or higher toxicities included malaise, fatigue, and/or lethargy (30%), leukopenia (14%), neutropenia (13%), dyspnea (13%), nausea (11%), and respiratory infection (6%). Forty-three patients discontinued treatment due to intolerable side effects. CONCLUSION: rIFN alpha-2a in the dose and schedule used in this study failed to prolong response duration or survival in patients with limited-stage SCLC who had previously responded to an induction chemoradiotherapy program. Failure may have been partly related to poor tolerance and inability to complete therapy.

Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group.

PURPOSE: This phase III randomized trial was designed to determine if granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicity and morbidity induced by chemoradiotherapy in limited-stage small-cell lung cancer (SCLC). METHODS: This multicenter prospective trial randomized 230 patients to receive chemotherapy and radiotherapy (RT) with or without GM-CSF given on days 4 to 18 of each of six cycles. The primary end point was hematologic toxicity. Secondary end points included the following: nonhematologic toxicities; days of (1) fever, (2) antibiotics, (3) hospitalization, and (4) infection; number of transfusions; drug doses delivered; and response rates and survival. RESULTS: There was a statistically significant increase in the frequency and duration of life-threatening thrombocytopenia (P < .001) in patients randomized to GM-CSF. GM-CSF patients had significantly more toxic deaths (P < .01), more nonhematologic toxicities, more days in hospital, a higher incidence of intravenous (IV) antibiotic usage, and more transfusions. Patients randomized to GM-CSF had higher WBC and neutrophil nadirs (P < .01), but no significant difference in the frequency of grade 4 leukopenia or neutropenia. Patients randomized to GM-CSF had a lower complete response rate (36% v 44%), but the differences were not significant (P = .29). There were no significant differences in survival (median, 14 months on GM-CSF and 17 months on no GM-CSF; P = .15). CONCLUSION: GM-CSF, as delivered in this study, should not be included with concurrent chemoradiotherapy treatment programs for limited-stage SCLC. The simultaneous use of hematopoietic colony-stimulating factors (CSFs) and chemoradiotherapy should be performed only in experimental settings. Chemoradiotherapy programs with cisplatin and etoposide ([VP-16] PE) and simultaneous chest RT produce grade 4 neutropenia and thrombocytopenia in a small-enough proportion of patients that prophylactic hematopoietic growth factors are clinically unnecessary.

Daily low-dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group study.

PURPOSE: This single-arm phase II trial was designed to evaluate the efficacy and toxicity of continuous-course, high-dose thoracic irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin. PATIENTS AND METHODS: Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (i.v.) cisplatin (5 mg/m2) plus concurrent continuous-course RT (61 Gy over 6 1/2 weeks) both delivered Monday through Friday each week. After a 3- to 4-week rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m2 or subsequently 50 mg/m2 administered i.v. on days 1 and 8 of each cycle. RESULTS: Sixty-four patients were eligible; the majority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity. Esophagitis (16%), leukopenia (14%), nausea (8%), and vomiting (6%) were the most common severe (grade 3) toxicities. There was only one life-threatening toxicity (grade 4 nausea) and no treatment-related deaths. The objective response rate was 39%, and six patients (9%) achieved a radiographic complete response (CR). The median survival duration for all patients was 14 months, and the 1- and 2-year actuarial survival rates were 56% and 24%, respectively. For stage IIIa patients, the median survival duration and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively. CONCLUSION: Daily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated out-patient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.

Results of primary and adjuvant CT-based 3-dimensional radiotherapy for malignant tumors of the paranasal sinuses.

PURPOSE: This study reports our clinical experience supporting the normal tissue-sparing capability of 3-dimensional (3-D) treatment planning when applied to advanced neoplasms of the paranasal sinuses. METHODS AND MATERIALS: Between 1986 and 1992, computed tomography (CT)-based 3-D radiotherapy was used to treat 39 patients with advanced stage malignant tumors of the paranasal sinuses as all or part of initial treatment. Fifteen unresectable patients were treated with primary radiotherapy to a median prescribed total dose of 68.4 Gy. Twenty-four patients were treated with postoperative adjuvant radiotherapy for close margins (< 5 mm), microscopic or gross residual disease. The median prescribed total doses were 55.8 Gy, 59.4 Gy and 67.8 Gy, respectively. Globe-sparing fields were used in the primary treatment plans of 37 patients (95%). The median follow-up is 4.5 years (range, 19-86 months). RESULTS: For the unresectable patients who were treated with radiotherapy alone, the local control rate at 3 years is 32%. The actuarial overall survivals at 3 and 4 years are 32%. For the patients who received postoperative adjuvant radiotherapy, none of the five patients irradiated for close surgical margins recurred locally. Three of the 14 with microscopic residual (21%) recurred locally at 26, 63, and 74 months from the start of irradiation. Four of the five with gross residual (80%) recurred locally with a median time to recurrence of 2 years. The local control rates at 3 and 5 years for the adjuvant group are 75% and 65%, respectively. The actuarial overall survival at 3 and 5 years are 65% and 60%, respectively. None of the first sites of local disease progression were judged to have occurred outside the high-dose region. There was one case of mild osteoradionecrosis successfully treated with conservative treatment, one case of limited optic neuropathy and one case of possible radiation-induced cataract. There was no blindness related to irradiation. CONCLUSION: This study indicates that computed tomography-based 3-D radiotherapy can preserve critical structures unaffected by tumor invasion and achieve the generally expected local control rates when it is used as all or part of initial treatment for extensive malignant tumors of the paranasal sinus. The presence of gross disease was a major adverse prognostic factor in this study. Additional therapeutic maneuvers are essential to improve the local control and survival rate in patients with advanced paranasal sinus carcinomas.

Dose-volume histogram and 3-D treatment planning evaluation of patients with pneumonitis.

PURPOSE: Tolerance of normal lung to inhomogeneous irradiation of partial volumes is not well understood. This retrospective study analyzes three-dimensional (3-D) dose distributions and dose-volume histograms for 63 patients who have had normal lung irradiated in two types of treatment situations. METHODS AND MATERIALS: 3-D treatment plans were examined for 21 patients with Hodgkin's disease and 42 patients with nonsmall-cell lung cancer. All patients were treated with conventional fractionation, with a dose of 67 Gy (corrected) or higher for the lung cancer patients. A normal tissue complication probability description and a dose-volume histogram reduction scheme were used to assess the data. Mean dose to lung was also calculated. RESULTS: Five Hodgkin's disease patients and nine lung cancer patients developed pneumonitis. Data were analyzed for each individual independent lung and for the total lung tissue (lung as a paired organ). Comparisons of averages of mean lung dose and normal tissue complication probabilities show a difference between patients with and without complications. Averages of calculated normal tissue complication probabilities for groups of patients show that empirical model parameters correlate with actual complication rates for the Hodgkin's patients, but not as well for the individual lungs of the lung cancer patients treated to larger volumes of normal lung and high doses. CONCLUSION: This retrospective study of the 3-D dose distributions for normal lung for two types of treatment situations for patients with irradiated normal lung gives useful data for the characterization of the dose-volume relationship and the development of pneumonitis. These data can be used to help set up a dose escalation protocol for the treatment of nonsmall-cell lung cancer.

Use of Veff and iso-NTCP in the implementation of dose escalation protocols.

PURPOSE: This report investigates the use of a normal tissue complication probability (NTCP) model, 3-D dose distributions, and a dose volume histogram reduction scheme in the design and implementation of dose escalation protocols for irradiation of sites that are primarily limited by the dose to a normal tissue which exhibits a strong volume effect (e.g., lung, liver). METHODS AND MATERIALS: Plots containing iso-NTCP contours are generated as a function of dose and partial volume using a parameterization of a NTCP description. Single step dose volume histograms are generated from 3-D dose distributions using the effective-volume (Veff) reduction scheme. In this scheme, the value of Veff for each dose volume histogram is independent of dose units (Gy, %). Thus, relative dose distributions (%) may be used to segregate patients by Veff into bins containing different ranges of Veff values before the assignment of prescription doses (Gy). The doses for each bin of Veff values can then be independently escalated between estimated complication levels (iso-NTCP contours). RESULTS AND CONCLUSION: Given that for the site under study, an investigator believes that the NTCP parameterization and the Veff methodology at least describe the general trend of clinical expectations, the concepts discussed allow the use of patient specific 3-D dose/volume information in the design and implementation of dose escalation studies. The result is a scheme with which useful prospective tolerance data may be systematically obtained for testing the different NTCP parameterizations and models.

Preservation of parotid function after external beam irradiation in head and neck cancer patients: a feasibility study using 3-dimensional treatment planning.

PURPOSE: Radiation-induced xerostomia is a frequent complication and major cause of morbidity in head and neck cancer patients. The severity of xerostomia is related to radiation dose and the amount of parotid tissue included in the irradiated volume. To reduce this side-effect and preserve salivary function, we have evaluated the use of 3-dimensional (3-D) treatment planning to spare the contralateral parotid gland in twelve patients undergoing radiation therapy for head and neck cancers. METHODS AND MATERIALS: In each case, beam's eye view displays were used to design beam and blocking arrangements that excluded the contralateral parotid. Ten patients were treated with 2 nonopposing oblique fields in the axial and non-axial plane while two patients required a non-axial, non-coplanar 3-field arrangement. These 3-D treatment plans were also compared with conventional 2-dimensional (2-D) plans. The 2-dimensional plans were designed independently of the 3-D treatment planning information using the orthogonal radiographs and hard copies of the computed tomography scans. RESULTS: An average of 1.8% (range, 0-7%) of the target volume was underdosed with the 95% isodose level for the 3-D plans compared with 18.8% (range, 2.0-36.6%) for the 2-D plans. This was due to improved identification of the target volumes and better design of blocked fields with beam's eye view treatment planning. Furthermore, the mean dose to the opposite parotid was 3.9 Gy for the 3-D plans vs 28.9 Gy for the conventional plans. With a minimum follow-up of 4 months, only 2 of 12 patients have complained of a dry mouth. CONCLUSION: These encouraging results suggest that this approach is feasible in many cases. 3-D treatment planning may allow the use of parotid sparing techniques in patients who otherwise would not have been considered candidates using conventional radiotherapy techniques.

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis.

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.

Spinal cord ependymomas treated with surgery and radiation therapy. A review of 11 cases.

Between 1971 and 1990, 11 patients with primary spinal cord ependymomas were treated with surgery and postoperative irradiation or surgery alone at the University of Colorado Health Sciences Center. Of the 11 patients, 6 (54%) were subclassified with myxopapillary ependymomas that were located in the lumbosacral region of the spinal cord: 2 patients underwent complete resections, 8 had subtotal resections, and 1 had a biopsy only; 8 patients received postoperative irradiation (range: 4,500-5,482 cGy) with 7 of 8 patients treated to involved spinal fields. With a mean follow-up of 7.4 years, 3 patients (27%) have developed recurrent disease, 2 in the combined treatment group, and 1 in the surgery alone group. The 5- and 10-year actuarial survival rates were 100% and 80%, respectively. Eight of nine patients (89%) demonstrated clinical improvement after postoperative irradiation which suggests that the irradiation may have contributed to the improvement. The present study supports the long-term survival of patients with spinal cord ependymomas. Results from this series and a review of the literature indicate that complete surgical resection is only possible in about one-quarter of cases. Local spinal irradiation should continue to be utilized when surgery is incomplete.

The evolving role of radiation therapy in the treatment of locally advanced lung cancer.

RT has been used routinely in the treatment of NSCLC and SCLC for the past several decades. Although largely considered a palliative treatment by most oncologists, there is increasing evidence that RT, when combined with cisplatin-based chemotherapy or given by altered fractionation, may improve the survival in NSCLC. Three large randomized trials have now shown that RT plus a cisplatin-based combination or cisplatin alone prolongs patient survival. Studies of hyperfractionation and accelerated hyperfractionation have also shown promise and are being tested in randomized trials worldwide. The results from these trials must be assessed against ongoing radiation dose escalation studies using new treatment planning technologies, albeit still in their infancy. These trials are discussed in this report. Systemic therapy is the cornerstone of treatment for SCLC. Although the value of RT was hotly debated during the 1970s and 1980s, it is now well established that RT improves survival when combined with chemotherapy in limited stage patients. Despite this advancement, other issues (such as timing or sequencing of modalities, radiation dose, fractionation, and treatment volume), remain unsettled. Randomized trials designed to address these important issues are in progress.

Multiple brain metastases are associated with poor survival in patients treated with surgery and radiotherapy.

PURPOSE: A retrospective analysis was performed to evaluate the role of surgery in the management of patients with solitary and multiple brain metastases. PATIENTS AND METHODS: Between 1980 and 1990, 46 patients underwent surgical resection of brain metastases at the University of Colorado Health Sciences Center. All but two patients received postoperative whole-brain radiotherapy to a median total dose of 30 Gy (range, 11.4 Gy to 50.0 Gy). Lung was the most common (56%) primary site and adenocarcinoma was the most common (46%) tumor histology. Twenty-eight of 46 patients (61%) had solitary metastases, while the remaining 18 patients had two or more foci. RESULTS: The median survival of all 46 patients was 11 months, and the 1- and 2-year survival rates were 40% and 12%, respectively. Moderately severe to severe neurologic impairment at the time of diagnosis and the presence of multiple brain metastases were associated with a significantly poorer survival. In patients with solitary metastasis, gross total resection and adenocarcinoma tumor histology significantly prolonged survival, whereas primary tumor site, the presence of active extracranial disease, and radiation dose had no significant effect on survival. CONCLUSION: These results are consistent with a recent randomized study supporting the role of surgery and whole-brain radiation therapy in the management of patients with solitary brain metastases. We would caution against the generalization of this concept to patients with two or more brain metastases.

Prostatic thermoluminescent dosimeter analysis in a patient treated with 18 MV X rays through a prosthetic hip.

External beam radiation therapy with high energy photon beams through hip prostheses has been shown to cause dose inhomogeneities for target volumes in the pelvis. In this work, measurements of dose using thermoluminescent dosimetry were compared with dose calculations from a computerized treatment planning system in a patient with prostatic carcinoma and a cobalt-chromium-molybdenum hip prosthesis. A 39% decrement in dose at isocenter was demonstrated for an 18 MV photon beam passing through the prosthesis. A discrepancy of only 3.1% was shown between measured and calculated dose when the tissue-maximum ratio (TMR) method of heterogeneity correction was used. However, it is recognized that several sources of error are possible when heterogeneity corrections are performed for high density prostheses and these are discussed below. The results of this work stress the importance of accurate data for use with the "ratio of TMR's" algorithm in order that accurate treatment planning can be performed.

Mediastinoscopy incisional metastasis. A radiotherapeutic approach.

Tumor seeding of the mediastinoscopy tract has been described. Although it is a rare occurrence, it can present the radiation oncologist with a therapeutic dilemma. Two cases of mediastinoscopy scar recurrences are reported. Their response to treatment and a review of previous cases are included.

Survival results in adult patients treated for medulloblastoma.

The records of all 27 adult patients (age, greater than or equal to 16 years) diagnosed with cerebellar medulloblastoma between 1968 and 1986 were reviewed. Twenty-four patients (89%) were treated with postoperative megavoltage irradiation. Twenty of these patients underwent craniospinal irradiation. Sixteen patients received greater than 5000 cGy to the posterior fossa (range, 2340 to 6600 cGy; median, 5490 cGy). Forty-eight percent of patients also received adjuvant chemotherapy. A 5-year and 10-year actuarial survival rate of 48% was achieved. The use of adjuvant chemotherapy did not improve survival in this series. All relapses occurred within 35 months of diagnosis (median time to relapse, 23.5 months), except one patient who had a recurrence in the posterior fossa at 140 months. The posterior fossa was the most common site of treatment failure and represented 50% of all initial relapses. All survivors had no sequelae, except one in whom leukoencephalopathy developed after craniospinal irradiation and intrathecal methotrexate administration. The survival results obtained in this series compare favorably with other reported modern adult medulloblastoma series.