SU-E-T-412: Can Cyberknife SBRT Be an Alternative to Brachytherapy for Cervical Cancer Treatment?

PURPOSE: To investigate the effectiveness of stereotactic body radiation therapy (SBRT) with Cyberknife for treatment of squamous cell carcinoma (SCCa) of cervix that are commonly treated with brachytherapy. METHODS: SCCa of cervix is routinely treated with external beam radiation therapy (EBRT) followed by brachytherapy. Common practice is to use high-dose- rate (HDR) brachytherapy, mainly with Ir-192; however, low-dose-rate (LDR) brachytherapy with Cs-137 is also used. Three of our patients with cervical SCCa who were chosen to have LDR brachytherapy (Cs-137 with tandem and ovoids) could not tolerate the prolonged treatment or applicator placement. All these patients previously received 45Gy (1.8Gy/fratction) from EBRT and well tolerated. Planned LDR treatment dose and time were for patient-1: 42.63Gy in 73.5hr, patient-2: 42.34Gy in 73hr, patient-3: 41.76Gy in 72hr. Delivered LDR dose and time were: 3.75Gy in 6.5hr, OGy in Ohr, and 17.3Gy in 19.8hr, for patient-1, -2 and -3, respectively. Two of the three patients tolerated LDR treatment partially; the second patient could not tolerate the applicator, which required immediate removal after placement. Treatments were completed with Cyberknife SBRT (CK-SBRT)doses of 25Gy, 15Gy and 25Gy for patient-1, -2 and -3, respectively; all had 5Gy/fraction and 3fractions/week. Prescriptions were at 80% isododelines; CTV coverages were 96.6%, 99.9% and 100% for patient-1, -2 and -3, respectively. RESULTS: Till their last follow-up in February 2012, all three patients were doing fine clinically without any evidence of disease; none of these patients had any complications that could be related to CK-SBRT. CONCLUSIONS: Appears that CK-SBRT can be a viable treatment alternative to brachytherapy. CK-SBRT may also be more appealing to patients and physicians for a variety of reasons such as out-patient procedure, shorter treatment time, no need for operating room, and no need for applicator insertion and tolerance. However, extensive clinical study is warranted in this regard.

SU-E-T-422: Lung SBRT Using Cyberknife: Technique and Treatment Outcome.

PURPOSE: At East Carolina University, we have been treating primary and secondary lung cancers with Cyberknife stereotactic body radiotherapy (CK- SBRT) since February 2009. Till October 2011, we have treated a total of 79 patients (83 sites). In this study, we present our experience in CK-SBRT and clinical outcome of the treated patients. METHODS: Of the 79 patients, 43 were female; age of the whole patient population ranged 33.2-89.7yrs (median=73.2yrs). Patients treated for primary lung cancer (n=57) had severe chronic obstructive pulmonary disease (COPD) and were not surgical candidates. Cyberknife robotic system with tracking techniques (Synchrony=52, XsiteLung=22, XsightSpine=5) were used. Majority of the patient (n=52) had multiple gold fiducials placed (1-6 placed; 1-4 tracked per patient) either percutaneously or bronchoscopically. CT images were used for dosimetric planning, by medical physicists, using Cyberknife MultiPlan software. Prescription doses were 25Gy-55Gy in 3-5 fractions (mean=48.2Gy, median=50Gy); doses were prescribed mainly to 80% isodoseline (range=75-96%, mean=81.4%). PTV margin varied from 0-7mm (mean±SD=3.2±1.4mm), based on the tumor locations; breathing patterns and cancer type. Dosimetric coverage of GTV and PTV were (mean±SD): 97.8±5% and 94.7±6.9%, respectively. The treatment response was assessed using either a CT or a PET scan or both. RESULTS: The median follow up was 13.1months (range 0.3-31.9 months). Overall response rate was 98.8% (CR=73.5%). Local failure free survival at one year was 84% for primary (n=57), 76% for recurrent (n=16) lung cancer and 100% for metastatic (n=10) tumors. The toxicity rate was low with one patient reported to have chest wall pain and one patient developed grade 3-4 radiation pneumonitis. CONCLUSIONS: In most of the cases tight PTV margins were used. Since the prescriptions were at 80% isodeose line with more than 94% PTV coverage, the treatment outcome appeared reasonable. Further study relating PTV margin, dosimetric coverage, and treatment outcome is in progress.

SU-E-T-623: Utilizing a Hybrid Optimizer to Improve Dose Conformity during IMRT Planning.

PURPOSE: For IMRT treatment planning, an index-dose based algorithm features a fast approach in optimizing beam shapes and weights, and the quasi-Newton method is adopted in segment weight optimization by many commercial products. By combining these two optimizers, we aim to improve IMRT plan quality by achieving better normal tissue sparing. METHODS: An IMRT plan was generated using an in-house treatment planning system in three steps: 1) optimize fluence using beamlet intensity modulation, 2) generate Multi-collimator leaf sequence and segment weights, 3) tune the segment shapes and weights as each segment treated as a single beam. A quick converge was achieved by the optimizer implementing the index-dose concept in step (1 and 3). To further improve the plan's quality, we optimized the segment weights via a quasi-Newton gradient search method where a convex objective function was constructed using both existing segment shapes and dose constraints defined by the planner. Thus, the segment shapes were optimized with index-dose, the shapes optimized with quasi-Newton, alternately. The new approach was evaluated with patient cases including prostate and head & neck. RESULTS: Both plans had equivalent tumor dose coverage. For the prostate case, the rectal dose was reduced by 6% for V60% and 2% for V10cc, respectively. For the head and neck, better sparing was observed for the spinal cord, the left parotid, and the larynx. CONCLUSIONS: Combining index-dose and quasi- newton gradient search can effectively improve sparing of normal tissues without sacrificing target dose coverage. This work indicates the potential of improving treatment plan quality by integrating different optimization methods.

Automatic segmentation of intra-treatment CT images for adaptive radiation therapy of the prostate.

We have been developing an approach for automatically quantifying organ motion for adaptive radiation therapy of the prostate. Our approach is based on deformable image registration, which makes it possible to establish a correspondence between points in images taken on different days. This correspondence can be used to study organ motion and to accumulate inter-fraction dose. In prostate images, however, the presence of bowel gas can cause significant correspondence errors. To account for this problem, we have developed a novel method that combines large deformation image registration with a bowel gas segmentation and deflation algorithm. In this paper, we describe our approach and present a study of its accuracy for adaptive radiation therapy of the prostate. All experiments are carried out on 3-dimensional CT images.

Feasibility of optimizing the dose distribution in lung tumors using fluorine-18-fluorodeoxyglucose positron emission tomography and single photon emission computed tomography guided dose prescriptions.

The information provided by functional images may be used to guide radiotherapy planning by identifying regions that require higher radiation dose. In this work we investigate the dosimetric feasibility of delivering dose to lung tumors in proportion to the fluorine-18-fluorodeoxyglucose activity distribution from positron emission tomography (FDG-PET). The rationale for delivering dose in proportion to the tumor FDG-PET activity distribution is based on studies showing that FDG uptake is correlated to tumor cell proliferation rate, which is shown to imply that this dose delivery strategy is theoretically capable of providing the same duration of local control at all voxels in tumor. Target dose delivery was constrained by single photon emission computed tomography (SPECT) maps of normal lung perfusion, which restricted irradiation of highly perfused lung and imposed dose-function constraints. Dose-volume constraints were imposed on all other critical structures. All dose-volume/function constraints were considered to be soft, i.e., critical structure doses corresponding to volume/function constraint levels were minimized while satisfying the target prescription, thus permitting critical structure doses to minimally exceed dose constraint levels. An intensity modulation optimization methodology was developed to deliver this radiation, and applied to two lung cancer patients. Dosimetric feasibility was assessed by comparing spatially normalized dose-volume histograms from the nonuniform dose prescription (FDG-PET proportional) to those from a uniform dose prescription with equivalent tumor integral dose. In both patients, the optimization was capable of delivering the nonuniform target prescription with the same ease as the uniform target prescription, despite SPECT restrictions that effectively diverted dose from high to low perfused normal lung. In one patient, both prescriptions incurred similar critical structure dosages, below dose-volume/function limits. However, in the other patient, critical structure dosage from the nonuniform dose prescription exceeded dose-volume/function limits, and greatly exceeded that from the uniform dose prescription. Strict compliance to dose-volume/ function limits would entail reducing dose proportionality to the FDG-PET activity distribution, thereby theoretically reducing the duration of local control. Thus, even though it appears feasible to tailor lung tumor dose to the FDG-PET activity distribution, despite SPECT restrictions, strict adherence to dose-volume/function limits could compromise the effectiveness of functional image guided radiotherapy.

Chemoradiation for locally advanced squamous cell carcinoma of the head and neck for organ preservation and palliation.

OBJECTIVES: To measure the efficacy and toxic effects of our chemoradiotherapy regimen by means of response and survival in patients with advanced squamous cell carcinoma of the head and neck (HNSCC) for organ preservation in resectable disease or palliation in unresectable disease. DESIGN: All patients underwent evaluation by the multidisciplinary head and neck cancer team, with pathological diagnosis and staging. All patients underwent assessment for response to therapy using results of physical examination and radiologic imaging. Patients were followed up at 3-month intervals for a planned period of 5 years. SETTING: Academic center. PATIENTS: Thirty-eight previously untreated patients with newly diagnosed HNSCC were treated from June 1, 1996, through December 31, 1998, of whom 20 had resectable and 18 had unresectable tumors. INTERVENTION: Patients received intravenous cisplatin, 100 mg/m(2) for 1 hour on days 1 and 29; a 24-hour continuous infusion of fluorouracil, 1000 mg/m(2) on days 1 through 4 and 29 through 32; and radiation therapy, 150 rad twice daily for 12 days. The patients were given a 7- to 10-day break, and radiation therapy was restarted on day 29 for 12 additional days (total dose, 7200 rad). MAIN OUTCOME MEASURES: Complete, partial, and total response rates; disease-free survival; overall survival; and toxic effects. RESULTS: Toxic effects of treatment were moderately severe, including grades III to IV mucositis (89%), neutropenia (71%), and renal toxic effects (8%). In the 18 patients in the unresectable group, complete response in the 17 primary tumors and 15 cervical nodal metastases was achieved in 12 (71%) and 9 (60%), respectively; in the 20 patients undergoing organ preservation, complete response rates were 100% in the 23 primary tumors and 15 cervical nodal metastases. Complete response for all 38 patients was achieved in 31 (82%). In the unresectable group, the Kaplan-Meier relapse-free survival estimate is 56%, with follow-up from 29 to 45 months. In the organ preservation group, 75% of patients are alive without disease, and 8 have been followed up for 36 to 48 months. Of the 5 patients who have died, only 2 died of disease, with recurrences at 13.0 and 16.5 months. CONCLUSIONS: Chemoradiotherapy consisting of cisplatin, fluorouracil, and twice-daily external beam radiation is highly effective in achieving durable complete responses in patients with resectable HNSCC undergoing organ preservation and patients with unresectable HNSCC undergoing palliation. Toxic effects of this regimen were moderate to severe.

Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified phase I/II trial.

BACKGROUND: A modified Phase I/II trial was conducted evaluating the incorporation of three-dimensional conformal radiation therapy into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III unresectable nonsmall cell lung carcinoma (NSCLC). The dose of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was increased. Endpoints included response rate, toxicity, and survival. METHODS: Sixty-two patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (area under the concentration curve [AUC], 6) and paclitaxel (225 mg/m(2) over 3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x 6) carboplatin (AUC, 2) and paclitaxel (45 mg/m(2)/3 hours) were initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy). RESULTS: The response rate to induction carboplatin/paclitaxel was 40%. Eight patients (13%) progressed on the induction phase. No dose-limiting toxicity was observed during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, however, only 8% developed Grade 3/4 esophagitis using Radiation Therapy Oncology Group criteria. The overall response rate was 52%. Survival rates at 1, 2, 3, and 4 years were 71%, 52%, 40%, and 36%, respectively, with a median survival of 26 months. The 1-, 2-, and 3-year progression free survival probabilities were 47%, 35%, and 29%, respectively. CONCLUSIONS: Incorporation of TCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Both locoregional and distant failure remain problematic in this population of patients.

Three-dimensional conformal radiation treatment planning and delivery for low- and intermediate-grade gliomas.

Three-Dimensional conformal radiation treatment (3D-CRT) planning and delivery is an external beam radiation therapy modality that has the general goal of conforming the shape of a prescribed dose volume to the shape of a 3-dimensional target volume, simultaneously limiting dose to critical normal structures. 3-Dimensional conformal therapy should include at least one volumetric imaging study of the patient. This image should be obtained in the treatment position for visualizing the target and normal anatomic structures that are potentially within the irradiated volume. Most often, computed tomography (CT) and/or magnetic resonance imaging (MRI) are used; however, recently, other imaging modalities such as functional MRI, MR spectroscopy, and positron emission tomography (PET) scans have been used to visualize the clinically relevant volumes. This article will address the clinically relevant issues with regard to low- and intermediate-grade gliomas and the role of 3D-CRT planning. Specific issues that will be addressed will include normal tissue tolerance, target definition, treatment field design in regard to isodose curves and dose-volume histograms, and immobilization.

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

The maximum tolerated dose of conformal radiation therapy delivered at 1.6 Gy bid is being assessed in patients with unresectable stage IIB-IIIB non-small cell lung cancer who have been treated with induction regimens consisting of carboplatin plus paclitaxel or carboplatin plus vinorelbine. Data from the early stages of this parallel phase I study show that the two induction regimens are similar in toxicity and that both induce partial responses in 45% of patients. Both regimens can be followed by conformal radiotherapy using an accelerated hyperfractionated schedule to a dose of at least 80 Gy without experiencing unacceptable toxicity. Key morbidity observed thus far has involved the esophagus. Further cohorts of patients will receive higher doses of conformal radiotherapy (in 6.4 Gy increments) until the maximum tolerated dose is reached.

Incorporating functional imaging information into radiation treatment.

Three-dimensional treatment planning systems allow the clinician to define tumor and normal anatomy of computed tomograpy (CT) scans and project the result onto a digitally reconstructed radiograph (DRR) for comparison with a simulation or portal film. Unfortunately, the CT scan does not always show the tumor accurately. First, the tumor may have either been removed surgically, or cytoreduced with chemotherapy before the treatment planning scan was taken. Or, the planning CT may not be the ideal imaging modality for a particular tumor, magnetic resonance imaging (MRI) or positron-emission tomography (PET) being much better. In either case, the nonplanning images provide more reliable data as to the position and extent of tumor than do the CT. A 3D/3D registration between the diagnostic and planning image must then be performed to make the data from both images available for the planning process. Methods of performing accurate 3D/3D registration of dissimilar images have been studied extensively by experts in image processing, but the techniques have not yet been fully adopted by the medical community. In addition, there is no standard way of dealing with the multiple tumor volumes that will be generated by full multimodality treatment planning. This article ends with speculation as to the extent to which multimodality image-based treatment planning can improve cancer treatment rates. New imaging modalities such as magnetic resonance spectroscopy, PET, or functional imaging, tuned to the particular tumor type, might reveal more than just the gross tumor volume seen on CT or MRI. One could imagine radiation treatment to many sites in the body under image guidance that would result in cure of metastatic disease, should the cancer be confined to a reasonable number of discrete sites.

Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified Phase I trial.

BACKGROUND: A modified Phase I trial was conducted evaluating the incorporation of 3-dimensional conformal radiation therapy (3DCRT) into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III, unresectable nonsmall cell lung carcinoma (NSCLC). In addition, dose escalation of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was performed. Endpoints included response rate, toxicity, and survival. METHODS: Twenty-nine patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (AUC 6) and paclitaxel (225 mg/m(2)/3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x6) carboplatin (AUC 2) and paclitaxel (45 mg/m(2)/3 hours) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts. RESULTS: The response rate to induction carboplatin/paclitaxel was 52%. Three patients (10%) experienced disease progression during the induction phase. No dose-limiting toxicity was seen during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, with 18% of patients developing Radiation Therapy Oncology Group Grade 3 esophagitis. The overall response rate was 70% (1 complete response and 18 partial responses). Survival rates at 1 and 2 years were 69% and 45%, with a median survival of 21 months. The 1-year progression free survival probability was 41% (95% confidence interval, 23-59%). CONCLUSIONS: Incorporation of 3DCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Accrual is continuing in a Phase II fashion at 74 Gy with sequential and concurrent carboplatin/paclitaxel.

[Burch laparoscopic procedure for repairing proven stress incontinence--report of 32 cases].

There are more than 200 procedures for repairing stress urinary incontinence. We evaluated the safety and efficiency of the Burch laparoscopic procedure in 32 women with urodynamically proven genuine stress incontinence. Mean operating time was 40 minutes and mean hospitalization time after the procedure was 30 hours. The cure rate was 97%, similar to that reported in other studies (80-95%). The major complications were 2 cases (6.2%) of unintended bladder injury, diagnosed and repaired laparoscopically. Although follow-up has only been for 3-42 months, the high cure rate and safety and advantages of laparoscopy over laparotomy, make laparoscopic Burch colposuspension the procedure of choice for repairing stress incontinence.

Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group.

PURPOSE: To determine whether the administration of carboplatin concurrently with radiation treatment improves survival in patients with inoperable stage III non-small-cell lung cancer. PATIENTS AND METHODS: Two hundred eighty-three patients with inoperable stage III non-small-cell lung cancer were entered onto a randomized trial by the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. Randomization was performed before initiation of any therapy. All patients received an induction chemotherapy program with vinblastine and cisplatin for 5 weeks, followed by 6,000 cGy of radiation therapy over 6 weeks. One hundred thirty-seven patients were randomized to this therapy regimen alone; 146 patients were randomized to receive carboplatin at 100 mg/m2/wk concurrent with the radiation therapy. RESULTS: The complete response was 18% with concurrent carboplatin versus 10% with radiotherapy alone (P = .101). There was no difference with respect to failure-free survival (10% with carboplatin and 9% with radiotherapy alone) or overall survival (13% with carboplatin and 10% with radiotherapy alone) at 4 years. In patients not receiving carboplatin, the relapse rate was 69% within the field of radiation and 53% in the boost volume. In patients receiving carboplatin, the relapse rate was 59% within the field of radiation and 43% in the boost volume. Patients with cancers more than 70 cm2 in size had significantly poorer survival (P = .01). CONCLUSION: Carboplatin at the dose and schedule used did not significantly impact on disease control or survival. The relapse rate within the chest remained more than 50%. More effective regimens will be required to impact on local disease control and survival.

Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer.

PURPOSE: An improvement in radiation dose schedule is necessary to increase local tumor control and survival in limited-stage small-cell lung cancer. The goal of this study was to determine the maximum-tolerated dose (MTD) of radiation (RT) in both standard daily and hyperfractionated-accelerated (HA) twice-daily RT schedules in concurrent chemoradiation. METHODS: The study design consisted of a sequential dose escalation in both daily and HA twice-daily RT regimens. RT dose to the initial volume was kept at 40 to 40.5 Gy, while it was gradually increased to the boost volume by adding a 7% to 11 % increment of total dose to subsequent cohorts. The MTD was defined as the radiation dose level at one cohort below that which resulted in more than 33% of patients experiencing grade > or = 4 acute esophagitis and/or grade > or = 3 pulmonary toxicity. The study plan included nine cohorts, five on HA twice-daily and four on daily regimens for the dose escalation. Chemotherapy consisted of three cycles of cisplatin 33 mg/m2/d on days 1 to 3 over 30 minutes, cyclophosphamide 500 mg/m2 on day 1 intravenously (IV) over 1 hour, and etoposide 80 mg/m2/d on days 1 to 3 over 1 hour every 3 weeks (PCE) and two cycles of PE. RT was started at the initiation of the fourth cycle of chemotherapy. RESULTS: Fifty patients were enrolled onto the study. The median age was 60 years (range, 38-79), sex ratio 2.3:1 for male to female, weight loss less than 5% in 73%, and performance score 0 to 1 in 94% and 2 in 6% of patients. In HA twice-daily RT, grade > or = 4 acute esophagitis was noted in two of five (40%), two of seven (29%), four of six (67%), and five of six patients (86%) at 50 (1.25 Gy twice daily), 45, 50, and 55.5 Gy in 1.5 Gy twice daily, 5 d/wk, respectively. Grade > or = 3 pulmonary toxicity was not seen in any of these 24 patients. Therefore, the MTD for HA twice-daily RT was judged to be 45 Gy in 30 fractions over 3 weeks. In daily RT, grade > or = 4 acute esophagitis was noted in zero of four, zero of four, one of five (20%), and two of six patients (33%) at 56, 60, 66, and 70 Gy on a schedule of 2 Gy per fraction per day, five fractions per week. Grade > or = 3 pneumonitis was not observed in any of the 19 patients. Thus, the MTD for daily RT was judged to be at least 70 Gy in 35 fractions over 7 weeks. Grade 4 granulocytopenia and thrombocytopenia were observed in 53% and 6% of patients, respectively, during the first three cycles of PCE. During chemotherapy cycles 4 to 5, grade 4 granulocytopenia and thrombocytopenia were noted in 43% and 29% of patients at 45 Gy in 30 fractions over 3 weeks (MTD) by HA twice-daily RT and 50% and 17% at 70 Gy in 35 fractions over 7 weeks (MTD) by daily RT, respectively. The overall tumor response consisted of complete remission (CR) in 51% (24 of 47), partial remission (PR) in 38% (1 8 of 47), and stable disease in 2% (one of 47). The median survival time of all patients was 24.4 months and 2- and 3-year survival rates were 53% and 28%, respectively. With regard to the different radiation schedules, 2- and 3-year survival rates were 52% and 25% for the HA twice-daily and 54% and 35% for the daily RT cohorts. CONCLUSION: The MTD of HA twice-daily RT was determined to be 45 Gy in 30 fractions over 3 weeks, while it was judged to be at least 70 Gy in 35 fractions over 7 weeks for daily RT. A phase III randomized trial to compare standard daily RT with HA twice-daily RT at their MTD for local tumor control and survival would be a sensible research in searching for a more effective RT dose-schedule than those that are being used currently.

Extending the indications for breast-conserving treatment to patients with locally advanced breast cancer.

PURPOSE: Breast-conserving therapy (BCS) has generally been limited to T1 and T2 lesions because it has been thought impossible to achieve good local control with satisfactory cosmesis in patients with more advanced disease. However, many patients with T3 and T4 lesions will exhibit dramatic tumor downstaging with neoadjuvant chemotherapy. It is our hypothesis that for these patients BCS can be performed with good local control and cosmesis. METHODS AND MATERIALS: Between February 1991 and November 1995, 34 patients with T3/T4, N0-N2, M0 breast cancer completed treatment consisting of 90 mg/m2 of doxorubicin every 21 weeks x 4, surgery (a local excision if sufficiently downstaged, or mastectomy if not), high dose cyclophosphamide (CMF) every 2 weeks x 4, and radiation therapy. Radionuclide ventriculograms were performed on all patients pre- and postdoxorubicin, and at 6-12 months post radiation therapy. Patients were evaluated for toxicity, local control, cosmesis, disease-free and overall survival. RESULTS: Median follow-up is 30 months. 15/34 (44%) patients underwent BCS with only one local-regional failure and actuarial 3-year disease-free and overall survival of 77% and 88%. Cosmetic results were good to excellent in 80% of the patients. Left ventricular ejection fraction, which predictably declined following doxorubicin, did not further decline after radiation therapy. CONCLUSIONS: These results suggest that with this regimen a subset of patients with locally advanced breast cancer can preserve their breast with acceptable cosmesis without compromising local control or survival.

Portfolio: a prototype workstation for development and evaluation of tools for analysis and management of digital portal images.

PURPOSE: The purpose of this investigation was to design and implement a prototype physician workstation, called PortFolio, as a platform for developing and evaluating, by means of controlled observer studies, user interfaces and interactive tools for analyzing and managing digital portal images. The first observer study was designed to measure physician acceptance of workstation technology, as an alternative to a view box, for inspection and analysis of portal images for detection of treatment setup errors. METHODS AND MATERIALS: The observer study was conducted in a controlled experimental setting to evaluate physician acceptance of the prototype workstation technology exemplified by PortFolio. PortFolio incorporates a windows user interface, a compact kit of carefully selected image analysis tools, and an object-oriented data base infrastructure. The kit evaluated in the observer study included tools for contrast enhancement, registration, and multimodal image visualization. Acceptance was measured in the context of performing portal image analysis in a structured protocol designed to simulate clinical practice. The acceptability and usage patterns were measured from semistructured questionnaires and logs of user interactions. RESULTS: Radiation oncologists, the subjects for this study, perceived the tools in PortFolio to be acceptable clinical aids. Concerns were expressed regarding user efficiency, particularly with respect to the image registration tools. CONCLUSIONS: The results of our observer study indicate that workstation technology is acceptable to radiation oncologists as an alternative to a view box for clinical detection of setup errors from digital portal images. Improvements in implementation, including more tools and a greater degree of automation in the image analysis tasks, are needed to make PortFolio more clinically practical.

[Recurrent tuberculosis in a psychiatric hospital, recurrent outbreaks during 1987-1996].

During 1987-1996, 39 of 720 patients hospitalized (most for severe schizophrenia) were diagnosed as having active pulmonary tuberculosis (5.4%, 975 per 105 per year). In 1992-1993, after a cluster of 5 cases was found, all patients were screened by PPD skin test and chest X-ray and 16 more cases were identified. Diagnosis was confirmed bacteriologically in only 10 of them but there were typical radiological findings in the others. 39 were treated with a multi-drug regimen. In addition, 333 exposed patients and 21% who had converted their skin tests were given isoniazid preventive therapy. A small increase in levels of liver enzymes was common, but significant abnormality (over 4 times the upper limit of normal) was found in only 7 patients, in whom therapy was therefore stopped or changed. During a follow-up period of 4 years, 2 more developed tuberculosis and 33 converted their PPD reactivity status. We conclude that an outbreak of tuberculosis in a psychiatric hospital can be controlled with a relatively low rate of side-effects by using systematic diagnostic and therapeutic measures. However, single step screening is not sufficient. Routine screening of all new patients, a high index of suspicion and contact investigation are needed.

Image registration: an essential part of radiation therapy treatment planning.

PURPOSE: We believe that a three-dimensional (3D) registration of nonplanning (diagnostic) imaging data with the planning computed tomography (CT) offers a substantial improvement in tumor target identification for many radiation therapy patients. The purpose of this article is to review and discuss our experience to date. METHODS AND MATERIALS: We reviewed the charts and treatment planning records of all patients that underwent 3D radiation treatment planning in our department from June 1994 to December 1995, to learn which patients had image registration performed and why it was thought they would benefit from this approach. We also measured how much error would have been introduced into the target definition if the nonplanning imaging data had not been available and only the planning CT had been used. RESULTS: Between June 1994 and December 1995, 106 of 246 (43%) of patients undergoing 3D treatment planning had image registration. Four reasons for performing registration were identified. First, some tumor volumes have better definition on magnetic resonance imaging (MRI) than on CT. Second, a properly contrasted diagnostic CT sometimes can show the tumor target better than can the planning CT. Third, the diagnostic CT or MR may have been preoperative, with the postoperative planning CT no longer showing the tumor. Fourth, the patient may have undergone cytoreductive chemotherapy so that the postchemotherapy planning CT no longer showed the original tumor volume. In patients in whom the planning CT did not show the tumor volume well an analysis was done to determine how the treatment plan was changed with the addition of a better tumor-defining nonplanning CT or MR. We have found that the use of this additional imaging modality changed the tumor location in the treatment plan at least 1.5 cm for half of the patients, and up to 3.0 cm for 1/4 of the patients. CONCLUSIONS: Multimodality and/or sequential imaging can substantially aid in better tumor definition in many patients undergoing 3D treatment planning. In some patients the appropriate nonplanning imaging source can change the perceived tumor location by several centimeters and is thus essential for proper treatment planning.

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

Three-dimensional visualization and image processing in the evaluation of patterned injuries. The AFIP/UNC experience in the Rodney King case.

We used image processing to elucidate patterned injuries in a case of assault with a police baton. Three-dimensional visualization techniques were then used to correlate the location of patterned injuries with subjacent fracture and soft tissue damage. The visualization methods are discussed.