Bidimensional Measurements Research Articles

Assessment of lung cancer response after nonoperative therapy: tumor diameter, bidimensional product, and volume. A serial ct scan-based study

Purpose: Tumor response after nonoperative lung cancer therapy is traditionally evaluated by bidimensional measurement of maximum tumor diameters. The purpose of this analysis is to investigate whether tumor largest dimension (based on RECIST [Response Evaluation Criteria In Solid Tumors]), bidimensional tumor product, and volume correlate with each other in evaluating tumors of patients with locally advanced non-small-cell lung cancer (NSCLC). In addition, the pace of locally advanced NSCLC volumetric response over time, as well as the prognostic value of tumor size, was assessed in this report with software-assisted evaluation of sequential tumor measurement. Methods and Materials: Patients with locally advanced NSCLC treated with thoracic radiotherapy (RT) with or without chemotherapy were included, if the following were available: a pretreatment computed tomography (CT) simulation and at least two follow-up diagnostic thoracic CT scans taken at our institution after 1996 that were available in Dicom format for electronic transfer of images from diagnostic radiology to a computer terminal with commercial statistics software (AcQsim/CMS Focus). Primary lung tumor and grossly involved lymph nodes were contoured manually on pre-RT axial images and on all follow-up CT scans. Tumor/lymph node largest dimensions, bidimensional products (BP), and volumes were measured using the same software. Data were presented as percent change in volume or unidimensional and bidimensional measurements, with the CT simulation measurements serving as baseline. Results: A total of 22 patients were evaluated. The median thoracic RT dose was 62.4 Gy (range: 50.0–69.6), and all patients had a Karnofsky performance status ≥80. Chemotherapy (mostly carboplatin/paclitaxel) was given to 17 patients. Nineteen patients had Stage III NSCLC; 1 patient was in Stage I, 1 was in Stage IV, and 1 was recurrent. A total of 107 thoracic CT scans (22 pretreatment and 85 follow-up), averaging 4.9 scans per patient, were analyzed. Tumors reached the smallest volume at a median of 11.0 months from RT completion in all patients, 8.5 months in patients who subsequently failed locally ( n = 8), and 11.9 months in those who did not fail locally. Failure rates were as follows: in-field, 36% (8/22); intrathoracic (lung nodules, effusion, pleura), 55% (12/22); and distant, 50% (11/22). Eleven patients are still alive, 4 free of disease. Overall median survival time (MST) is 27.3 months. The median initial tumor volume was 88.0 cc (range: 3.8–218) for all patients; median BP was 33.0 cm 2 (range: 3.1–112.1), and median tumor largest dimension was 7.6 cm (range: 2.2–13.5). The MST of patients with initial tumor volume ≤63.0 cc ( n = 9) was >53.0 months and of those with tumor volume >63.0 cc was 17.3 months. The MST of patients ( n = 6) with initial bidimensional tumor product ≤16 cm 2 was >53.0 months and of those with tumor product >16 cm 2 was 17.3 months. The MST of patients with largest initial dimension ≤4 cm was >53.1 months and of those with largest dimension >4 cm was 25.0 months. At 24 months, 79% of patients with a tumor volume ≤124.0 cc ( n = 18) had locally controlled tumors, vs. 0% of patients with tumor volumes >124.0 cc. At the same time point, 93% of patients with BP ≤40 cm 2 were locally controlled, vs. 0% of those with BP >40 cm 2; 100% of patients with tumor dimensions ≤7.5 cm were locally controlled, vs. 40% of those with dimensions >7.5 cm. The partial responses in our series (assessed as the best response obtained during observation period) were as follows: 4 patients assessed based on either dimension only, product only, or volume only; 15 partial responses based on dimension or product; 16 partial responses based on volume alone; 3 cases of no tumor response, based on dimension or product; and 2 cases based on tumor volume alone. That represents good to excellent agreement among all three methods of measurement. Conclusions: ( 1) The response of locally advanced NSCLC to nonoperative therapy is a slow process, with tumor volumes reaching their nadir several months after treatment. ( 2) Smaller initial tumor size, as measured by largest tumor dimension, bidimensional product, or tumor volume, is associated with better local control and survival than larger initial measurements. ( 3) Any of the three tumor measurements (largest dimension, bidimensional product, or volume) can be used as a reliable tool in assessing lung cancer response to nonoperative therapy. This confirms further the validity of RECIST and does not suggest that tumor volume is significantly superior for response evaluation.

Comparison of Unenhanced and Contrast-Enhanced Spiral CT for Assessing Interval Change in Patients with Colorectal Liver Metastases

Rationale and Objectives The purpose of this study was to determine whether the interval change in hepatic colorectal metastases as assessed with serial computed tomographic (CT) scans without contrast material enhancement differs from that as assessed using serial, portal dominant phase, contrast-enhanced CT scans. Materials and Methods Unenhanced and contrast-enhanced abdominal CT scans were obtained in 28 patients. Three radiologists separately reviewed serial unenhanced and contrast-enhanced studies to assess the interval change in liver metastases. These radiologists recorded total number of lesions, bidimensional measurements of the largest lesions (as many as three), and overall impressions regarding the interval change (none, worse, or better). Results Among the 84 judgments (28 patients × 3 radiologists), comparisons of unenhanced and contrast-enhanced CT studies were concordant in 60 assessments (71%). Nineteen (23%) showed mild disagreement. Of these, contrast-enhanced CT studies demonstrated disease stability when unenhanced CT studies demonstrated otherwise in 11 judgments, whereas unenhanced CT studies demonstrated stability when contrast-enhanced CT studies demonstrated otherwise in eight assessments. Furthermore, of the five marked disagreements, two resulted from a conclusion of interval improvement on unenhanced CT studies and a conclusion of interval worsening on contrast-enhanced CT studies, whereas three demonstrated the opposite. Neither set of serial CT studies systematically resulted in under- or overestimation of disease progression (McNemar Q test, P < .25). Conclusion The authors found no consistent pattern to demonstrate that serial unenhanced or contrast-enhanced CT studies resulted in over- or underestimation of disease progression.

Tumor size on computed tomography scans

Bidimensional tumor measurements are used routinely as surrogates for tumor volume. The purpose this study was to determine whether there is any added benefit in bidimensional or tridimensional measurements over a unidimensional measurement. Sixty-nine colorectal hepatic metastases on 19 computed tomography scans (1-8 lesions per scan) from 9 patients were analyzed. Five patients contributed 2-4 scans each (mean, 3 scans). The standard volume of these lesions was determined by the "summation of areas" technique. The maximum axial dimension, the product of the greatest axial dimensions, and several volume estimates (based on the volumes of a sphere, an ellipsoid, and a cube) each were correlated with the standard volume. The maximum axial dimension and the product of the greatest axial dimensions correlated equally with tumor volume (correlation coefficient = 0.93). Surrogate measures based on the equations for a sphere and an ellipsoid underestimated tumor volume, whereas the equation for a cube overestimated volume. When reporting tumor size, there is no significant added benefit in reporting bidimensional or tridimensional measurements over the maximum axial dimension.

Ovarian cancer — difficulties in monitoring response.

Ovarian cancer — difficulties in monitoring response.

Problems in the assessment of treatment response

Problems in the assessment of treatment response

Commentary. Are current tumour response criteria relevant for the 21st century?

Monitoring the response of tumours to treatment is an integral and increasingly important function of oncological radiologists. Imaging studies allow an objective method of quantifying tumour response to a variety of physical and pharmaceutical treatments. Current morphological imaging techniques depict tumour response as changes in tumour size and composition [1]. Objective tumour shrinkage has been widely adopted as a standard end-point for selecting new anti-cancer drugs for further study, as a prospective end-point for de®nitive clinical trials designed to estimate the bene®t of treatment in a speci®c group of patients, and is widely used in everyday clinical practice to guide clinical decision-making. Measurement of lesions should whenever possible be bidimensional, by multiplying the largest diameter by its perpendicular to give the product. Criteria for assessing therapeutic response were ®rst proposed in 1981 and, although they have been adapted by various cancer organizations, continue to be used largely unchanged [2]. Recently, the World Heath Organisation has adopted a revised set of size criteria incorporating unidimensional measurements (RECIST criteriaÐResponse Evaluation Criteria in Solid Tumours, June 1999) for assessing tumour response [3]. There are many recognized limitations of size change as a tumour response variable. Size changes for both response and progression are arbitrary and are traditionally expressed as a percentage change from baseline. For example, a minimum of 50% reduction in lesion size (equivalent to a 75% reduction in volume) is needed before documenting a partial response to treatment. When multiple lesions are present, all the products are summed. In contrast, progressive disease is de®ned as an increase of 25% in the size of one or more lesions, or as the appearance of new lesion(s). Measurements performed in this way are laborious and beset by numerous errors. These arise from observer variations of the estimated position of the boundary of lesions. The edges of irregular or in®ltrating lesions are often dif®cult to identify and some tumours are impossible to measure; for example, pulmonary lymphangitis carcinomatosa and ovarian carcinoma seeding into the peritoneal space. Furthermore, there is no consensus on whether necrosis and cystic change should be included or excluded when obtaining tumour measurements. The dif®culty in distinguishing peritumoral ®brosis from tumour spread further confounds attempts at measurement. Measurement errors in estimating the size of small lesions often result in misclassi®cation of tumour response; for example, Lavin and Flowerdew [4] showed that the currently used 25% increase in size of lesions can result in a one in four chance of declaring that progression has occurred when in fact the tumour is unchanged [4]. So serious are these errors that ``independent review panels'' are often employed by pharmaceutical companies to standardize the reporting of tumour response in clinical trials. Independent review panels can disagree with ``home radiologists'' in 50% of cases, with major disagreements occurring in up to 40% [5]. The causes for such disagreements include variations in examination technique for obtaining images, in lesion selection and in siting the edges of target lesions. Bidimensional size criteria do not take full account of tumour volume, while state-of-the-art imaging machines can routinely acquire such information. However, three-dimensional volume measurements are likely to encounter errors similar to bidimensional size measurements. A change in size may also be delayed chronologically, often requiring several treatments before a decision can be made on whether a treatment is effective. Reports from the functional imaging literature, particularly positron emission tomography (PET), suggest that metabolic and physiological changes antecede size change [6]. For example, in patients with lymphoma responding to treatment, changes in energetics can be Received 4 January 2000 and in revised form 27 April 2000, accepted 19 May 2000.

Evaluation of tumor measurements in oncology: use of film-based and electronic techniques.

To evaluate the variability in bidimensional computed tomography (CT) measurements obtained of actual tumors and of tumor phantoms by use of three measurement techniques: hand-held calipers on film, electronic calipers on a workstation, and an autocontour technique on a workstation. Three radiologists measured 45 actual tumors (in the lung, liver, and lymph nodes) on CT images, using each of the three techniques. Bidimensional measurements were recorded, and their cross-products calculated. The coefficient of variation was calculated to assess interobserver variability. CT images of 48 phantoms were measured by three radiologists with each of the techniques. In addition to the coefficient of variation, the differences between the cross-product measurements of tumor phantoms themselves and the measurements obtained with each of the techniques were calculated. The differences between the coefficients of variation were statistically significantly different for the autocontour technique, compared with the other techniques, both for actual tumors and for tumor phantoms. There was no statistically significant difference in the coefficient of variation between measurements obtained with hand-held calipers and electronic calipers. The cross-products for tumor phantoms were 12% less than the actual cross-product when calipers on film were used, 11% less using electronic calipers, and 1% greater using the autocontour technique. Tumor size is obtained more accurately and consistently between readers using an automated autocontour technique than between those using hand-held or electronic calipers. This finding has substantial implications for monitoring tumor therapy in an individual patient, as well as for evaluating the effectiveness of new therapies under development.

KAPOSI'S SARCOMA RESPONSE CRITERIA

Currently utilized Kaposi's Sarcoma (KS) response criteria evaluate cutaneous disease on the basis of lesion number, lesion characteristics (flat vs raised) and bidimensional measurements of marker lesions. Pulmonary KS is evaluated by standard solid tumor response criteria while KS response in other visceral sites (e.g., gastrointestinal tract) is frequently not well documented. The evaluation of KS response has been criticized because of difficulties in reproducibility and documentation of lesion counts and measurements, the lack of a standard assessment of visceral disease and the failure of these criteria to capture the clinical benefits(e.g., resolution of KS-associated pain, edema, disfigurement) of KS treatment. Investigators from the National Cancer Institute (NCI), the Food and Drug Administration (FDA) and the AIDS Malignancy Consortium (AMC) are in the process of revising KS response criteria and are seeking to identify clinically meaningful, reproducible, and practical endpoints to monitor the response to therapy of KS. These criteria may affect the design and conduct of clinical trials, as well as facilitate drug development. Evaluation of clinical benefit is complex in KS. The new criteria will focus on tumor specific symptoms, and include evaluation both from the physician and patient perspectives. Categories considered significant include: pain; edema, particularly extremity, scrotal, and facial; facial and oral lesions; visceral related symptoms, and lesion necrosis/ulceration. Subjective evidence of clinical benefit should be supported by objective measurements relevant to the symptom and is essential in uncontrolled and/or unblinded trials. For example, a reduction in pain or improvement in mobility due to improvement in edema should be supported by photographs or measurements. After systematic consideration of the typical symptoms and findings in KS, new response criteria will be proposed. The usefulness of these new criteria will be determined in prospective clinical trials.

Another Look at Induction Chemotherapy for Organ Preservation in Patients With Head and Neck Cancer

chemotherapy followed by radiotherapy as its new standard for comparison of future organ-sparing strategies. The EORTC trial design differed from other induction chemotherapy trials in some respects. First, only patients achieving a CR on endoscopic evaluation were offered organsparing therapy. One could speculate that this resulted in better local control (similar to surgically treated patients) than occurred in the VA Laryngeal Cancer Study that was less selective, allowing partial responders (PR) to receive radiotherapy. In reality, it is quite difficult to obtain accurate bidimensional measurements of a lesion visualized in the larynx or hypopharynx to document a PR. Second, endoscopy alone was used to clinically evaluate response after each course of chemotherapy; computed tomographic imaging was recommended but not required. Third, the decision to perform a neck dissection before radiotherapy for patients with a CR at the primary but residual disease in the neck was left to the treating physician, not mandated. These variances served to streamline the study, focusing on the main question of feasibility of organ preservation and survival, and do not detract from the results. This protocol used a well-establish ed chemotherapy regimen (cisplatin at 100 mg/m2 on day 1 + infusional 5-FU at 1000 mg/m2 per day for 5 days repeated every 3 weeks). The 86% response rate (54% CR + 32% PR) of the primary is in the expected range. Compliance was excellent: 95% of the patients (89 of 94) in the surgery arm received the planned treatment as did 93% of the patients (93 of 100) randomized to receive chemotherapy. Only six patients randomized to receive induction chemotherapy for whom surgery was recommended refused to undergo laryngopharyngectomy per protocol. There was one treatment-related death during induction chemotherapy and no increase in surgical complications after chemotherapy. The EORTC trial was well designed and executed. A uniform patient population with respect to site, stage, and operability was studied with the use of an optimal drug regimen. Furthermore, the sample size was adequate to formulate conclusions with

P28 Response criteria in solid tumours: UNI-dimensional vs BI-dimensional measurements

P28 Response criteria in solid tumours: UNI-dimensional vs BI-dimensional measurements

P28 Response criteria in solid tumours: UNI-dimensional vs BI-dimensional measurements

P28 Response criteria in solid tumours: UNI-dimensional vs BI-dimensional measurements

Response of oral leukoplakia to beta-carotene.

Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta-carotene. Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer.