Biomedical subjects

Julian G Rosenman

Publications and source records attributed to Julian G Rosenman.

10 recordsLinked to original sources

PubMed2006

Post-chemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy.

PURPOSE: To evaluate the influence of clinical covariates, particularly pre-chemotherapy gross tumor volume (GTV), post-chemotherapy GTV, on overall survival in the treatment of stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: We retrospectively analyzed 102 patients who were enrolled on three consecutive clinical trials, which employed the treatment paradigm of two cycles of induction chemotherapy followed by thoracic radiation therapy. The pre-chemotherapy GTV, post-chemotherapy GTV, change in GTV, histology, disease stage, performance status, age, race, treatment with concurrent chemoradiotherapy versus radiotherapy alone were evaluated to determine their impact on overall survival. The log10 of the GTV was used to normalize the data and thereby reduce the impact of exceptionally large values. RESULTS: Both the log10 of the post-chemotherapy GTV and Eastern Cooperative Oncology Group (ECOG) performance status covariates were highly prognostic for overall survival (p = 0.006 and p = 0.008, respectively). Disease stage (at diagnosis) was also significant (p = 0.048). The log10 pre-chemotherapy GTV covariate was borderline significant (p = 0.067). The strongest prognostic model was the two-covariate model, which contained the log10 post-chemotherapy GTV and ECOG performance status covariates, (model chi2 of 18.67, with p = 0.001 for each covariate). CONCLUSIONS: The log10 post-chemotherapy GTV has significant prognostic survival value when the strategy of induction chemotherapy is employed in the treatment on stage III NSCLC. ECOG performance status and stage were also significant prognostic factors for survival.

Adult↗

PubMed2005

Does more aggressive therapy improve outcomes in the treatment of unresectable stage III non-small cell lung cancer?

Concurrent chemotherapy combined with radiation therapy currently offers the best treatment strategy in stage IIIA/IIIB non-small cell lung cancer. However, inadequate radiation dose may be a contributing factor in the resultant lack of adequate control of local disease. Hypothetically, radiation doses that are higher than "standard" (eg, 60 Gy) might increase patient morbidity without improving cure rates, and data from a University of North Carolina phase I/II trial suggested that at least 74 Gy can be given safely to patients receiving cytotoxic chemotherapy, with a trend toward improved survival. Also, clinical data indicate that the cytoprotective agent amifostine (Ethyol; MedImmune Inc, Gaithersburg, MD) can be used to reduce esophagitis (and possibly pneumonitis) in patients treated with conventional radiation doses. Finally, a phase III clinical trial is proposed to: (1) test the hypothesis that higher radiation doses lead to a survival advantage in non-small cell lung cancer patients; and (2) discern the value of amifostine as a cytoprotective agent in the high-radiation dose range.

Amifostine↗

PubMed2005

Chemotherapeutic issues in the management of unresectable stage III non-small cell lung cancer.

The standard of care in unresectable stage IIIA/B non-small cell lung cancer is combined-modality therapy using both chemotherapy and thoracic radiation therapy. Although there is general agreement on this principle, there remain many controversies regarding the optimal combined-modality approach in this patient population. Both induction and concurrent chemoradiotherapy strategies were initially tested, with both approaches improving survival in randomized phase III trials. Several trials have now been completed comparing sequential versus concurrent approaches. There appears to be a modest and consistent advantage to the concurrent approach at the risk of an increase in the rates of acute toxicities, particularly esophagitis and myelosuppression. The concurrent approach used in the phase III trials evaluating the question of sequence has been the use of full-dose systemic chemotherapy rather than a low-dose radio-enhancing strategy. These approaches are distinctly different, and one must recognize this difference when evaluating results from clinical trials. A number of clinical trials have established the use of both induction and consolidation chemotherapy; however, the optimal approach remains unclear. What is clear is that this population of patients needs aggressive therapy directed at achieving locoregional control as well as control of occult micrometastatic disease that is present in the majority of cases. As treatment strategies have become more aggressive, survival outcomes have improved, although the differences have been modest at best, and the risk of severe toxicity has increased. Future aggressive approaches must enhance both locoregional and distant control of occult disease, with acceptable rates of both acute and long-term toxicities.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer.

PURPOSE: We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing. METHODS: Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods. RESULTS: Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS. CONCLUSION: A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PURPOSE: Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. PATIENTS AND METHODS: Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. RESULTS: Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Compensators: an alternative IMRT delivery technique.

Seven years of experience in compensator intensity-modulated radiotherapy (IMRT) clinical implementation are presented. An inverse planning dose optimization algorithm was used to generate intensity modulation maps, which were delivered via either the compensator or segmental multileaf collimator (MLC) IMRT techniques. The in-house developed compensator-IMRT technique is presented with the focus on several design issues. The dosimetry of the delivery techniques was analyzed for several clinical cases. The treatment time for both delivery techniques on Siemens accelerators was retrospectively analyzed based on the electronic treatment record in LANTIS for 95 patients. We found that the compensator technique consistently took noticeably less time for treatment of equal numbers of fields compared to the segmental technique. The typical time needed to fabricate a compensator was 13 min, 3 min of which was manual processing. More than 80% of the approximately 700 compensators evaluated had a maximum deviation of less than 5% from the calculation in intensity profile. Seventy-two percent of the patient treatment dosimetry measurements for 340 patients have an error of no more than 5%. The pros and cons of different IMRT compensator materials are also discussed. Our experience shows that the compensator-IMRT technique offers robustness, excellent intensity modulation resolution, high treatment delivery efficiency, simple fabrication and quality assurance (QA) procedures, and the flexibility to be used in any teletherapy unit.

Algorithms↗

PubMed2004

A preliminary study of the role of modulated electron beams in intensity modulated radiotherapy, using automated beam orientation and modality selection.

PURPOSE: To develop an algorithm for optimal beam arrangement selection in intensity-modulated radiotherapy (IMRT) of mixed photon and electron beams. To apply this algorithm to study the utility of modulated electron beams in the context of IMRT planning. METHODS AND MATERIALS: The optimization algorithm selects, for a user-specified number of beams, the optimal IMRT arrangement (beam orientations, and photon/electron modality for each orientation) using a novel fast heuristic intensity modulation procedure. The algorithm was employed to select optimal beam arrangements for breast (two, four, and six axial beams) and head-and-neck (three, four, five, and seven nonaxial beams) cases. RESULTS: For the two cases, increasing the number of selected beams: (1) increased the number of electron beams for the breast case, but not more than one electron beam was selected for the head-and-neck case; (2) decreased critical structure doses for both cases; and (3) decreased target homogeneity for the breast case, but improved it for the head-and-neck case. CONCLUSIONS: In the two cases analyzed using the selection algorithm, the primary role of modulated electrons differs based on treatment site-normal tissue dose reduction in breast and target homogeneity improvement in head and neck. Although this preliminary study with two cases appears to suggest that the role of intensity-modulated electrons differs based on treatment site, further investigation of large numbers of cases and varied treatment sites are required to establish a definitive conclusion.

Algorithms↗

PubMed2004

Dosimetry of a prototype retractable eMLC for fixed-beam electron therapy.

An electron multileaf collimator (eMLC) has been designed that is unique in that it retracts to 37 cm from the isocenter [63-cm source-to-collimator distance (SCD)] and can be deployed to distances of 20 and 10 cm from the isocenter (80 and 90 cm SCD, respectively). It is expected to be capable of arc therapy at 63 cm SCD; isocentric, fixed-beam therapy at 80 cm SCD; and source-to-surface distance (SSD), fixed-beam therapy at 90 cm SCD. In all positions, its leaves could be used for unmodulated or intensity-modulated therapy. Our goal in the present work is to describe the general characteristics of the eMLC and to demonstrate that its leakage characteristics and dosimetry are adequate for SSD, fixed-beam therapy as an alternative to Cerrobend cutouts with applicators once the prototype's leaves are motorized. Our eMLC data showed interleaf electron leakage at 15 MeV to be less than 0.1% based on a 0.0025 cm manufacturing tolerance, and lateral electron leakage at 5 and 15 MeV to be less than 2%. X-ray leakage through the leaves was 1.6% at 15 MeV. Our data showed that beam penumbra was independent of direction and leaf position. The dosimetric properties of square fields formed by the eMLC were very consistent with those formed by Cerrobend inserts in the 20 x 20 cm2 applicator. Output factors exhibited similar field-size dependence. Airgap factors exhibited almost identical field-size dependence at two SSDs (105 and 110 cm), consistent with the common assumption that airgap factors are applicator independent. Percent depth-dose curves were similar, but showed variations up to 3% in the buildup region. The pencil-beam algorithm (PBA) fit measured data from the eMLC and applicator-cutout systems equally well, and the resulting two-dimensional (2-D) dose distributions, as predicted by the PBA, agreed well at common airgap distance. Simulating patient setups for breast and head and neck treatments showed that almost all fields could be treated using similar SSDs as when using applicators, although head and neck treatments require placing the patient's head on a head-holder treatment table extension. The results of this work confirmed our design goals and support the potential use of the eMLC design in the clinical setting. The eMLC should allow the same treatments as are typically delivered with the electron applicator-cutout system currently used for fixed-beam therapy.

Air↗

PubMed2002

High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial.

PURPOSE: We completed a Phase I/II clinical trial (Lineberger Comprehensive Cancer Center 9603), in which we treated 62 Stage IIIA/IIIB inoperable non-small-cell lung cancer (NSCLC) patients with two cycles of induction carboplatin/paclitaxel chemotherapy, followed by concurrent weekly carboplatin/paclitaxel with radiation doses escalated from 60 to 74 Gy. The median survival of 24 months, 3-year survival rate of 38%, and the high dose of radiation used justified a critical analysis of the technical and clinical components of this trial. METHODS AND MATERIALS: Between 1996 and 1999, 62 sequential patients with inoperable Stage IIIA/IIIB NSCLC were enrolled and treated with two cycles of induction carboplatin (area under the concentration curve = 6 using the Calvert equation) and paclitaxel (225 mg/m(2)), followed by an escalating radiation dose of 60-74 Gy with concurrent carboplatin weekly (area under the concentration curve = 2) and paclitaxel weekly (45 mg/m(2)). The goals of the trial were to determine whether 74 Gy of radiation could be safely delivered under these circumstances and whether patients could potentially benefit in terms of survival. The radiation treatment plans for all 62 patients were reviewed to determine the prechemotherapy and postchemotherapy tumor volume, as well as the dose-volume histograms of the normal lung and esophagus. RESULTS: Of the 62 patients who entered the trial, 48 completed the entire course of treatment. At last follow-up, 20 patients were alive (crude survival rate 32%). With a median follow-up of 43 months, the median survival was 24 months. The survival rate was 50% at 2 years and 38% at 3 years. Cox regression analysis showed that survival was best predicted by whether the patient had received radiotherapy (finished the trial), performance status, disease stage, and log postchemotherapy tumor volume. The 3-year survival rate for the 48 patients finishing the trial was 45%. Eight patients (13%) suffered locoregional relapse as the only site of failure. Only 1 patient had Grade 2 radiation pneumonitis. Five patients (8%) had Radiation Therapy Oncology Group Grade 3 or 4 esophagitis; 40 (65%) had a Grade 1 or 2 esophagitis. Esophageal toxicity could be predicted by the length of esophagus receiving 40 or 60 Gy. CONCLUSION: Radiation doses of 74 Gy, when given under the guidelines of the Lineberger Comprehensive Cancer Center 9603, appear to be safe and may possibly contribute to increased survival in patients with inoperable Stage IIIA/IIIB NSCLC.

Adult↗

PubMed2002

Dose optimization via index-dose gradient minimization.

This paper presents an iterative optimization algorithm based on gradient minimization of index dose, defined as the product of physical dose and a numerical index. Acting as a template the index distribution is designed to represent the dosimetry that meets the dose volume histogram-based optimization objectives. The treatment dosimetry is optimized when the uniformity of the index-dose distribution is maximized. Prior to optimization the user can select all or only some of the beams to be intensity modulated. The remaining unmodulated beams can be either open or wedged photon beams, electron beams, or beams of previous treatments. The optimization result and treatment delivery efficiency can often be enhanced by including not only the IM photon beams but also all suitable fixed-beams available on the linac in the treatment plan. In addition, the doses from previous treatments can also be considered in the optimization of current treatment. Five clinical examples with different complexities in optimization objective are presented. The effects of two nonoptimization variables, beam setup and initial beam weights, on the quality of the dose optimization are also presented. The results are analyzed in terms of isodose distribution, dose volume histograms, and a dose optimization quality factor. The optimization algorithm, implemented in our in-house TPS PLanUNC, has been used in clinical application since 1996. The primary advantages of our optimization algorithm include computational efficiency, intensity modulation selection choice, and performance reliability for a wide range of clinical beam setups and optimization objectives.

Algorithms↗