3D quantitative assessment of response to fractionated stereotactic radiotherapy and single-session stereotactic radiosurgery of vestibular schwannoma.

OBJECTIVES: To determine clinical outcome of patients with vestibular schwannoma (VS) after treatment with fractionated stereotactic radiotherapy (FSRT) and single-session stereotactic radiosurgery (SRS) by using 3D quantitative response assessment on MRI. MATERIALS: This retrospective analysis included 162 patients who underwent radiation therapy for sporadic VS. Measurements on T1-weighted contrast-enhanced MRI (in 2-year post-therapy intervals: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12 years) were taken for total tumour volume (TTV) and enhancing tumour volume (ETV) based on a semi-automated technique. Patients were considered non-responders (NRs) if they required subsequent microsurgical resection or developed radiological progression and tumour-related symptoms. RESULTS: Median follow-up was 4.1 years (range: 0.4-12.0). TTV and ETV decreased for both the FSRT and SRS groups. However, only the FSRT group achieved significant tumour shrinkage (p < 0.015 for TTV, p < 0.005 for ETV over time). The 11 NRs showed proportionally greater TTV (median TTV pre-treatment: 0.61 cm(3), 8-10 years after: 1.77 cm(3)) and ETV despite radiation therapy compared to responders (median TTV pre-treatment: 1.06 cm(3); 10-12 years after: 0.81 cm(3); p = 0.001). CONCLUSION: 3D quantification of VS showed a significant decrease in TTV and ETV on FSRT-treated patients only. NR had significantly greater TTV and ETV over time. KEY POINTS: Only FSRT not GK-treated patients showed significant tumour shrinkage over time. Clinical non-responders showed significantly less tumour shrinkage when compared to responders. 3D volumetric assessment of vestibular schwannoma shows advantages over unidimensional techniques.

Brain-sparing total meningeal radiation for a patient with widespread progressive meningiomas using helical intensity modulated radiation.

Multiple meningioma is a rare but difficult clinical entity. We describe the case of a patient with widespread progressive meningiomas who could not safely have surgery or radiosurgery. We have previously treated these patients with whole brain radiation, despite the risks of neuropsychological side effects. In this case, we treated with a novel use of helical intensity modulated radiation therapy: brain-sparing total meningeal radiation. The brain-sparing technique allowed us to treat the patient's meninges with higher doses than would have been possible with whole brain radiation and with the goal of achieving long-term disease control.

Pretreatment ADC Values Predict Response to Radiosurgery in Vestibular Schwannomas.

BACKGROUND AND PURPOSE: The response rate of vestibular schwannomas to radiation therapy is variable, and there are surgical options available in the event of treatment failure. The aim of this study was to determine whether pre- and posttreatment ADC values can predict the tumor response to radiation therapy. MATERIALS AND METHODS: From a data base of 162 patients with vestibular schwannomas who underwent radiation therapy with gamma knife, CyberKnife, or fractionated stereotactic radiation therapy as the first-line therapy between January 2003 and December 2013, we found 20 patients who had pretreatment ADC values. There were 108 patients (including these 20) had serial MR images that included DWI allowing calculated ADC values from 2-132 months after radiation therapy. Two reviewers measured the mean, minimum, and maximum ADC values from elliptical ROIs that included tumor tissue only. Treatment responders were defined as those with a tumor total volume shrinkage of 20% or more after radiation therapy. RESULTS: The pretreatment mean minimum ADC for nonresponders was 986.7 × 10-6 mm2/s (range, 844-1230 × 10-6 mm2/s) and it was 669.2 × 10-6 mm2/s (range, 345-883 × 10-6 mm2/s) for responders. This difference was statistically significant (P < .001). Using a minimum ADC value of 800 × 10-6 mm2/s led to the correct classification of 18/20 patients based on pretreatment ADC values. The intraclass correlation between reviewers was 0.61. No posttreatment ADC values predicted response. CONCLUSIONS: Pretreatment ADC values of vestibular schwannomas are lower in responders than nonresponders. Using a minimum ADC value of 800 × 10-6 mm2/s correctly classified 90% of cases.

Phase II study of continuous infusion carmustine and cisplatin followed by cranial irradiation in adults with newly diagnosed high-grade astrocytoma.

PURPOSE: To evaluate the activity and toxicity of carmustine (BCNU) and cisplatin administered as a 72-hour continuous intravenous infusion before radiation in adults with newly diagnosed high-grade astrocytomas. PATIENTS AND METHODS: Fifty-two patients with a Karnofsky performance status greater than 60 and no prior antineoplastic therapy entered this protocol. The median age of the patients was 55 years. Eighty-eight percent had glioblastoma multiforme and 12% had anaplastic astrocytomas. BCNU (40 mg/m2/d) and cisplatin (40 mg/m2/d) were administered concurrently as a 72-hour infusion every 3 to 4 weeks. Radiation was begun 4 weeks after the third cycle of chemotherapy or earlier for progressive disease. Responses required a > or = 50% reduction in contrast-enhancing volume. RESULTS: Forty patients (77%) completed three chemotherapy infusions, five (10%) received two infusions, and seven (13%) received only one. Fifty-one patients completed radiation. Seventeen (42%) patients with measurable disease had a partial response (PR) to chemotherapy, 23 (53%) had stable disease (SD), and two (4%) had progressive disease (PD) on chemotherapy. The median survival time for all patients was 13 months. Survival rates at 1, 2, 3, and 5 years were 62%, 19%, 12%, and 5%, respectively. Grade III to IV leukopenia occurred in 32% of patients; 63% received platelet transfusions and 58% required RBCs. Neutropenic fevers were rare and no intracranial hemorrhages or treatment-related deaths were noted. Nausea, vomiting, peripheral neuropathy, hearing loss, and thromboembolic events were relatively common. CONCLUSION: This chemotherapy regimen appears to have significant activity and may prolong survival in adults with newly diagnosed high-grade astrocytoma.

Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme.

PURPOSE: To determine the safety, pharmacokinetics, and pharmacodynamic effect of 2-[4-(3, 5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylproprionic++ + acid (RSR13) 100 mg/kg/d with radiation therapy (RT) for glioblastoma multiforme (GBM). RSR13, a synthetic allosteric modifier of hemoglobin (HgB), is a novel radioenhancing agent that noncovalently binds to HgB, thereby reducing oxygen binding affinity and increasing tissue oxygen release to hypoxic tissues. PATIENTS AND METHODS: In this multi-institutional, dose frequency-seeking trial, 19 adult patients with newly diagnosed GBM received RSR13 100 mg/kg every other day or daily along with cranial RT (60 Gy/30 fractions). RSR13 was given over 1 hour by central venous access with 4 L/min of O(2 )by nasal cannula, followed by RT within 30 minutes. Pharmacokinetic (PK) and pharmacodynamic (PD) determinations were performed. The PD end point was shift in P50, the oxygen half-saturation pressure of HgB. RESULTS: Grade 3 dose-limiting toxicity occurred in none of the patients with every-other-day dosing and in two of the 10 patients with daily dosing. Grade 2 or greater toxicity occurred in three out of nine and six out of 10, respectively. PK and PD data demonstrate that a substantial PD effect was reliably achieved, that PD effect was related to RBC RSR13 concentration, and that there was no significant drug accumulation even with daily dosing. The mean shift in P50 was 9.24 +/- 2.6 mmHg (a 34% increase from baseline), which indicates a substantial increase in tendency toward oxygen unloading. CONCLUSION: Daily RSR13 (100 mg/kg) during cranial RT is well tolerated and achieves the desired PD end point. A phase II trial of daily RSR13 for newly diagnosed malignant glioma is currently accruing patients within the New Approaches to Brain Tumor Therapy Central Nervous System Consortium to determine survival outcome.

Survival of patients with newly diagnosed glioblastoma multiforme treated with RSR13 and radiotherapy: results of a phase II new approaches to brain tumor therapy CNS consortium safety and efficacy study.

PURPOSE: The objectives of this phase II study were to determine survival, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 2,4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid (RSR13, efaproxiral) 100 mg/kg per day administered with standard cranial radiotherapy (RT) for the treatment of glioblastoma multiforme (GBM). RSR13, a synthetic allosteric modifier of hemoglobin, is a radiation-enhancing agent that noncovalently binds to hemoglobin, reduces oxygen-binding affinity, and increases oxygen unloading to hypoxic tissue. PATIENTS AND METHODS: Fifty patients with newly diagnosed GBM (Karnofsky performance status >or= 60) were enrolled onto this multicenter phase II study. Patients received daily RSR13 100 mg/kg intravenously infused for 30 minutes immediately before cranial RT (60 Gy in 30 fractions). Supplemental oxygen was given during RSR13 infusion and continued until after the RT treatment was completed. RT was given within 30 minutes of the end of RSR13 infusion. PK and PD determinations were performed. RESULTS: The median survival for the RSR13-treated patients was 12.3 months with 1-year and 18-month survival rates of 54% and 24%, respectively. Twenty-four percent of patients had greater than grade 2 toxicity, which was generally transient and self-limited. A significant PD effect on hemoglobin-oxygen binding affinity was demonstrated for most patients. CONCLUSION: RSR13 (100 mg/kg) administered immediately before cranial RT is well tolerated and is pharmacodynamically active. Median survival in excess of 1 year is favorable.

Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus.

PURPOSE: This phase II trial evaluated continuous-infusion cisplatin and fluorouracil (5-FU) with radiotherapy followed by esophagectomy. The objectives of this trial were to determine the complete pathologic response rate, survival rate, toxicity, pattern of failure, and feasibility of administering adjuvant chemotherapy in patients with resectable cancer of the esophagus treated with preoperative chemoradiation. PATIENTS AND METHODS: Patients were staged using computed tomography, endoscopic ultrasound, and laparoscopy. The preoperative treatment plan consisted of continuous intravenous infusion of cisplatin and 5-FU and a total dose of 44 Gy of radiation. Esophagogastrectomy was planned for approximately 4 weeks after the completion of chemoradiotherapy. Paclitaxel and cisplatin were administered as postoperative adjuvant therapy. RESULTS: Forty-two patients were enrolled onto the trial. Of the 39 patients who proceeded to surgery, 29 responded to preoperative treatment: 11 achieved pathologic complete response (CR) and 18 achieved a lower posttreatment stage. Five patients had no change in stage, whereas eight had progressive disease (four with distant metastases and four with increases in the T and N stages). At a median follow-up of 30.2 months, the median survival time has not been reached and the 2-year survival rate is 62%. The median survival of pathologic complete responders has not been reached, whereas the 2-year survival rate of this group is 91% compared with 51% in patients with complete tumor resection with residual tumor (P =.03). CONCLUSION: An excellent survival rate, comparable to that of our prior preoperative trial, was achieved with lower doses of preoperative cisplatin and 5-FU concurrent with radiotherapy.

Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration.

BACKGROUND AND PURPOSE: A hyperintense appearance of the dentate nucleus on T1-weighted MR images has been related to various clinical conditions, but the etiology remains indeterminate. We aimed to investigate the possible associations between a hyperintense appearance of the dentate nucleus on T1-weighted MR images in patients exposed to radiation and factors including, but not limited to, the cumulative number of contrast-enhanced MR images, amount of gadolinium administration, dosage of ionizing radiation, and patient demographics. MATERIALS AND METHODS: The medical records of 706 consecutive patients who were treated with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and 2010 were blindly reviewed by 2 readers. RESULTS: One hundred eighty-four subjects were included for dentate nuclei analysis. Among the 184 subjects who cumulatively underwent 2677 MR imaging studies following intravenous gadolinium administration, 103 patients had hyperintense dentate nuclei on precontrast T1-weighted MR images. The average number of gadolinium-enhanced MR imaging studies performed in the group with normal dentate nuclei was significantly lower than that of the group with hyperintense dentate nuclei. The average follow-up time was 62.5 months. No significant difference was observed between hyperintense and normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine and calcium/phosphate levels, patient demographics, history of chemotherapy, and strength of the scanner. No dentate nuclei abnormalities were found on the corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS: Repeat performance of gadolinium-enhanced studies likely contributes to a long-standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR images.

Outcome of Adult Brain Tumor Consortium (ABTC) prospective dose-finding trials of I-125 balloon brachytherapy in high-grade gliomas: challenges in clinical trial design and technology development when MRI treatment effect and recurrence appear similar.

OBJECTIVES: The aim of this study is to define the maximal safe radiation dose to guide further study of the GliaSite balloon brachytherapy (GSBT) system in untreated newly diagnosed glioblastoma (NEW-GBM) and recurrent high-grade glioma (REC-HGG). GBST is a balloon placed in the resection cavity and later filled through a subcutaneous port with liquid I-125 Iotrex, providing radiation doses that diminish uniformly with distance from the balloon surface. METHODS: The Adult Brain Tumor Consortium initiated prospective dose-finding studies to determine maximum tolerated dose in NEW-GBM treated before standard RT or after surgery for REC-HGG. Patients were inevaluable if there was progression before the 90-day posttreatment toxicity evaluation point. RESULTS: Ten NEW-GBM patients had the balloon placed, and 2/10 reached the 90 day timepoint. Five REC-HGG enrolled and two were assessable at the 90-day evaluation endpoint. Imaging progression occurred before 90-day evaluation in 7/12 treated patients. The trials were closed as too few patients were assessable to allow dose escalation, although no dose-limiting toxicities (DLTs) were observed. Median survival from treatment was 15.3 months (95 % CI 7.1-23.6) for NEW-GBM and 12.8 months (95 % CI 4.2-20.9) for REC-HGG. CONCLUSION: These trials failed to determine a maximum tolerated dose (MTD) for further testing as early imaging changes, presumed to be progression, were common and interfered with the assessment of treatment-related toxicity. The survival outcomes in these and other related studies, although based on small populations, suggest that GSBT may be worthy of further study using clinical and survival endpoints, rather than standard imaging results. The implications for local therapy development are discussed.

Good performance status of long-term disease-free survivors of intracranial gliomas.

PURPOSE: To determine the long-term impact on function of treatment for primary cerebral gliomas, Karnofsky Performance Status, employment history, and memory function were used to evaluate the status of adults who are alive and disease-free more than 1 year after cranial irradiation. METHODS AND MATERIALS: Of 30 eligible adult patients, seventeen patients had anaplastic astrocytoma, seven had a glioblastoma, four had low grade astrocytoma, one had a mixed glioma, and one had an anaplastic oligodendroglioma. Sixteen patients received partial brain irradiation only, 12 had whole brain irradiation with a partial brain boost, and two had whole brain irradiation only. The total dose ranged from 54-66 Gy, with a fraction size of 1.7-2.0 Gy. Median follow-up was 3.5 years. Eighty-three percent of patients also received adjuvant chemotherapy. RESULTS: Karnofsky Performance Status generally remained stable after the completion of irradiation. Mean Performance status was 84 at the end of irradiation and was unchanged at the time of last follow-up. The actuarial freedom from performance status decline after irradiation was 93% at 5 years. The performance status increased in two patients, both within several months of completing irradiation. Most patients (68%) returned to work after irradiation. Sixty-two percent remained at work 1 year later, and 58% were working at the time of last follow-up. No patient who did not return to work within 4 months of completing irradiation was able to work at a later date. All working patients were employed in a capacity similar to their pre-morbid position. Only one patient, with an intercurrent lung cancer, eventually developed deficits that limited self care. CONCLUSIONS: Contrary to previously published reports, long-term glioma survivors maintained a relatively good performance status in the absence of recurrence and did not experience a progressive decline in neuropsychologic function after completion of cranial irradiation. A patient's function state at the completion of irradiation is a reliable predictor of long-term functional outcome in the absence of recurrence. Although the number of patients in each subgroup is small and no significant differences could be detected, patients treated with partial brain irradiation had a higher and more stable performance status, better memory function, and superior employment history.

The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma.

PURPOSE: To determine the effects of sequential versus concurrent administration of cranial radiotherapy and cisplatin/carmustine (BCNU) chemotherapy on survival and toxicity in newly diagnosed high-grade astrocytomas. METHODS AND MATERIALS: From 1988 to 1996, 101 patients were treated on 2 therapeutic protocols for malignant glioma that used the identical chemotherapy regimen but differed in the timing of cranial radiotherapy. The eligibility criteria for the 2 protocols were identical. In the first protocol (1988-1991, 52 patients), cisplatin 120 mg/BCNU 120 mg i.v. over 72 h, was given for 3 monthly cycles prior to cranial radiotherapy. After a response rate of 42%, with a median survival of 13 months was achieved with this sequential regimen, a successor protocol (1992-1996, 49 patients) was developed in which cranial radiotherapy began concurrently with the start of the identical chemotherapy regimen. Chemotherapy was delayed but not discontinued if prolonged grade III/IV hematologic toxicity was experienced, but protocol therapy was discontinued if disease progression or thromboembolic events occurred. Survival outcome and hematologic toxicity were compared for the patients treated on these protocols. RESULTS: Seventy-seven percent of sequentially-treated patients and 68% of concurrently-treated patients completed all planned therapy. Kaplan-Meier survival was similar to concurrent or sequential administration of chemotherapy and radiotherapy (median 12.8 months vs. 13.8 months, respectively). Hematologic toxicity was significantly less in sequentially- versus concurrently-treated patients, with median nadir per cycle (2.9 vs. 1.8 x 10(3)/mm3) (p < 0.001), and incidence of grade 3/4 leukopenia 40% versus 77% (p = 0.002). There was also an increase in platelet transfusion requirements in concurrently-treated patients, but no significant worsening of anemia. We postulate that the worsened leukopenia results from the effects of concurrent radiotherapy on circulating stem cells. CONCLUSION: Concurrent radiotherapy with this regimen of cisplatin and BCNU chemotherapy did not improve survival, but did increase hematologic toxicity. Therefore, we do not recommend further testing of the concurrent regimen, whereas the sequential regimen is currently under evaluation in a Phase III trial of the Eastern Cooperative Oncology Group and the Southwest Oncology Group. In addition, these studies demonstrate that relatively small radiotherapy fields can deliver a dose to circulating stem cells sufficient to worsen the hematologic toxicity of concurrent myelosuppressive chemotherapy, a phenomena which should be considered in the design of combined modality protocols for other body sites.

Short course radiotherapy is an appropriate option for most malignant glioma patients.

PURPOSE: To determine whether a shortened course of radiotherapy (RT) is an appropriate treatment option for malignant glioma patients. METHODS AND MATERIALS: Prognostic groups published by the Radiation Therapy Oncology Group (RTOG) are used to compare results for a short radiotherapy regimen with results of aggressive protocol treatment. The study group includes 219 patients treated during 1975-1993 with 51 Gy in 17 fractions. Patients were retrospectively assigned to six prognostic groups previously identified in a recursive partitioning analysis of the RTOG. The prognostic groups are based on age, histology, performance status, mental status, neurologic function, resection extent, length of symptoms, and RT dose. RESULTS: The six RTOG prognostic groupings were significantly predictive of outcome for patients treated with this shortened regimen (log-rank, p < 0.001). The median survival for our patients by RTOG groups 1-6 were 68, 57, 22, 13, 8, and 5 months, respectively. Two-year survival results were 64, 67, 45, 8, 3, and 3%. The median and two-year survival results for each prognostic grouping were similar to the results achieved by aggressive treatment on RTOG malignant glioma trials for selected patients. Treatment toxicity was uncommon. CONCLUSION: This shortened regimen is an appropriate treatment option for most malignant glioma patients (RTOG groups 4-6), resulting in similar survival as standard regimens with reduced patient effort and cost. Although acute side effects are acceptable and the risk of brain necrosis is low, we do not recommend this treatment to the minority of patients who have a substantial long term survival probability (RTOG groups 1-3) because long term neurocognitive assessment is lacking.

Treatment-related symptoms during the first year following transperineal 125I prostate implantation.

PURPOSE: To summarize the urinary, rectal, and sexual symptoms occurring during the first 12 months following 125I prostatic implantation. METHODS AND MATERIALS: Thirty-one patients with Stage T1 or T2 prostatic carcinoma were evaluated for morbidity following computed tomography-guided transperineal 125I implants from 1988 to 1991. The median total activity used was 47 mCi (range 35-73 mCi). Toxicity was evaluated using a modification of the Radiation Therapy Oncology Group grading system. RESULTS: Nocturia was the most common treatment-related symptom, reported by 80% of patients within 2 months after implantation, and persisted at 12 months in 45% of the patients. Mild dysuria developed in 48% of patients within 2 months of implantation; two patients needed analgesics for their dysuria. Terazosin hydrochloride (2-10 mg qd) provided subjective improvement of urinary symptoms in seven of eight patients in whom it was tried. Rectal urgency, soft stools, and increased frequency of bowel movements was reported by 25% of the patients within 1-2 months after implantation. The incidence of asymptomatic rectal bleeding or ulceration occurring at any time after implantation was 47%, but resolved in all patients with expectant treatment. Self-limited ulceration of the rectal mucosal occurred in 16%, but only one patient developed a prostato-rectal fistula, managed with an ileal conduit. Five of the 18 potent patients experienced discomfort on erection or ejaculation, beginning within several weeks of their implant. The discomfort resolved within 6 months in three of the patients, but persisted for 18 and 24 months in the other two. CONCLUSION: 125I implantation, as performed in this series, is generally associated with only mild-moderate genitourinary and rectal symptoms that may persist 6 months or more after implantation. Prostatic carcinoma, Brachytherapy, Morbidity.

Multimodality therapy for esophageal cancer.

Over the past decade and a half, several strategies have been developed to improve the survival of patients with esophageal cancer. Two strategies employ either neoadjuvant chemotherapy or chemoradiotherapy followed by surgery to improve local-regional control and decrease the incidence of distant metastases. A third strategy uses nonsurgical therapy as definitive treatment for patients without metastatic disease. Single-institution pilot trials and randomized comparative trials have been conducted evaluating each approach. The rationale for these trials, results, and current recommendations are presented.

Neoadjuvant chemoradiation followed by surgery for resectable esophageal cancer.

Neoadjuvant chemoradiation (NAC) therapy protocols were developed to improve survival in patients with resectable esophageal cancer. Our experience with two consecutive NAC therapy trials is reviewed. Both studies included patients with localized squamous cell cancer and adenocarcinoma. Patients were treated with cisplatinum 26 mg/m2/day (days 1-5 and 26-30), 5-Fluorouracil (5-FU) 300 mg/m2/day (days 1-30), concurrent radiotherapy (4400 cGy) followed by esophagectomy. In the second trial, adjuvant taxol was added. The first protocol had 50 patients. Two patients died, both before surgery, one from sepsis. There was no residual viable tumor (CR) in 19 (40%) patients. The median survival time was 31 months. The 5-year survival rate of 36% compared favorably with concurrent 5-year survival of 18% for surgery alone. Forty-one patients were enrolled in the second trial. All underwent surgery. There were no treatment or operative deaths. Survival data for this group is maturing. Combined results from both protocols are: treatment mortality of 2.2%, complete response rate of 37%, and a median and 3-year disease-specific survival of 42 months and 54%, respectively. We conclude that NAC followed by surgery improves survival over surgery alone and that CR is predictive of improved survival.

A dose texture plot in a moving frame as a new planning tool for single-plane implants in HDR brachytherapy.

A dose-texture plot is a print of dose values on the points of interest in a super-plane. The super-plane is a moving frame across the treatment depth-surface(s) with a fixed distance from surgical bed. The moving frame has an axis tangent to the midline of two neighboring catheters and the other axis perpendicular to the midline. By setting the scales of the two axes in units of the dwell step-size and the local distance between the two catheters, we can easily locate the basal-dose points with pairs of integers. A dose-texture plot on the basal-dose points in the super-plane provides the dose and location information in one picture. Such a picture can concisely represent the dose distribution in the treatment depth and allows us to quickly and quantitatively evaluate the effect of the source-dwell times and positions. This treatment-planning-evaluation tool has been used for development of an iteration optimization algorithm. The results of the iteration optimization on clinical cases demonstrated significant improvements over the optimization algorithms used in a commercial planning system.

Nonsegmental ventilation-perfusion scintigraphy mismatch after radiation therapy.

PURPOSE: This report illustrates the utility of ventilation-perfusion scintigraphy in differentiating radiation pneumonitis from other causes of dyspnea, including pulmonary embolism, heart failure, obstructive tumor, and chronic obstructive pulmonary disease. METHODS AND RESULTS: A nonsegmental mismatched perfusion abnormality, which exactly conformed to a radiation port, was diagnostic of radiation pneumonitis. CONCLUSION: In patients with lung tumors presenting with dyspnea, ventilation-perfusion scintigraphy may be useful in diagnosing radiation pneumonitis and effectively excluding other causes of dyspnea.