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Madhu Mazumdar

Publications and source records attributed to Madhu Mazumdar.

18 recordsLinked to original sources
PubMed2003

Response assessment classification in patients with advanced renal cell carcinoma treated on clinical trials.

BACKGROUND: The objective of the current study was to evaluate the effect on response assessment classification in patients with metastatic renal cell carcinoma (RCC) using unidimensional (Response Evaluation Criteria in Solid Tumors) and bidimensional (World Health Organization) criteria, including or excluding measurements of the primary renal tumor and using a new index to compensate for the disproportionate effect of large renal tumors relative to their metastases. METHODS: Fifty-three imaging studies involving a total of 44 patients with metastatic RCC who were treated on clinical trials of interferon-alpha analogue and/or thalidomide were reviewed retrospectively. The best overall response assessment and progression free survival were calculated with both unidimensional and bidimensional tumor measurements. Patients were then stratified into two groups: patients with primary renal tumors in situ and patients who underwent resection of their primary renal tumors. The best overall response and the time to disease progression were calculated based on the sum of measurements (conventional methodology), both including and excluding the primary tumor. A new method of response assessment, the 'normalized lesion index', which equalizes the differences in tumor size for an individual patient, was evaluated and compared with the conventional response assessment. RESULTS: There was an 11% disagreement rate in the best overall response assessment between unidimensional and bidimensional measurements. The time to progression was 9.2 months measured unidimensionally, compared with 6.4 months assessed bidimensionally. In the group of patients who had primary renal tumors in situ, using the conventional sum of measurements method, the apparent time to progression was an average of 4.2 months longer compared with measurements that did not include the primary renal tumor. The use of the normalized lesion index method resulted in an improved concordance in best overall response assessments and similar time to progression assessments when the primary renal tumor was included compared with patients who did not have primary renal tumors in situ. CONCLUSIONS: The use of unidimensional measurements in RCC therapy assessment results in significantly different time to progression classification compared with the use of bidimensional measurements. Response assessment classification in patients with RCC is affected by the exclusion or inclusion of measurements of the primary renal tumor. The normalized lesion index warrants further study in assessing response in patients with metastatic RCC and other solid tumor malignancies that often show substantial differences in sizes of measurable lesions.

Adult↗
PubMed2003

Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma.

PURPOSE: Few published studies have addressed individual patient risk after R0 resection for gastric cancer. We developed and internally validated a nomogram that combines these factors to predict the probability of 5-year gastric cancer-specific survival on the basis of 1,039 patients treated at a single institution. METHODS: Nomogram predictor variables included age, sex, primary site (distal one-third, middle one-third, gastroesophageal junction, and proximal one-third), Lauren histotype (diffuse, intestinal, mixed), number of positive lymph nodes resected, number of negative lymph nodes resected, and depth of invasion. Death as a result of gastric cancer was the predicted end point. The concordance index was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. RESULTS: Gastric cancer-specific survival at 5 years was 50%. A nomogram was constructed on the basis of a Cox regression model. The bootstrap-corrected concordance index was 0.80. When compared with the predictive ability of American Joint Committee on Cancer stage, the nomogram discrimination was superior (P <.001). Nomogram calibration appeared to be excellent. CONCLUSION: A nomogram was developed to predict 5-year disease-specific survival after R0 resection for gastric cancer. This tool should be useful for patient counseling, follow-up scheduling, and clinical trial eligibility determination.

Adult↗
PubMed2003

Variability in response assessment in solid tumors: effect of number of lesions chosen for measurement.

PURPOSE: This study was performed to systematically evaluate the variability in tumor response assessments that occurs depending on how many tumor deposits are selected for measurement at imaging. EXPERIMENTAL DESIGN: The two largest perpendicular diameters of all tumor deposits in 36 patients were measured on computed tomography scans obtained at baseline and first posttherapy follow-up. A computerized modeling analysis of those data was performed to determine each patient's therapeutic response category assignment for every possible number of lesions in a grouping. The variance in the sum of measurements of these lesion groupings was calculated, and the frequency of response assessment categories was plotted against the number of lesions. RESULTS: The computerized analysis of the resultant 1,833,821 possible combinations of tumor deposits showed that when six lesions were measured bidimensionally and four lesions were measured undimensionally, the average variance decreased by 90%. The number of different response assessment categories into which a patient was assigned decreased with increasing lesion grouping size. When six or more lesions were measured bidimensionally, 9% of all possible lesion groupings still fell into a second response category, reflecting the effect of which particular lesions are chosen for measurement. CONCLUSIONS: Measuring larger numbers of lesions will decrease the variance. In this population, the variance decreased by at least 90% when six or more lesions were measured bidimensionally. Further confirmatory studies with larger series of patients are warranted before adopting this number as a criterion in clinical trials for assessing the activity of antineoplastic therapies.

Adult↗
PubMed2003

Cluster analysis of p53 and Ki67 expression, apoptosis, alpha-fetoprotein, and human chorionic gonadotrophin indicates a favorable prognostic subgroup within the embryonal carcinoma germ cell tumor.

PURPOSE: The prognostic information provided by alpha-fetoprotein and human chorionic gonadotrophin in the management of germ cell tumor (GCT) patients is a biochemical reflection of tumor differentiation. Ki67, p53, and apoptosis have been found to be related to proliferation (Ki67), cell death (p53, apoptosis), and possibly differentiation chemoresistance (p53). We sought to determine whether simultaneous expression of one or more of these markers could identify clinically relevant subgroups of patients with nonseminomatous GCT (NSGCT). PATIENTS AND METHODS: These five marker values were obtained for 95 previously untreated patients with embryonal carcinoma with or without other germ cell components. A multivariate cluster analysis was performed to identify patients with similar marker patterns. RESULTS: One prominent cluster (n = 37; 36 testis retroperitoneum), consisting of 26 (70%) good-risk (GR), nine (24%) intermediate-risk (IR), and two (6%) poor-risk (PR) patients, as defined by the International Germ Cell Consensus Cancer Group (IGCCCG), was observed. The 5-year survival of the prominent cluster (with 30% IR/PR patients) was 94% (95% confidence interval [CI], 86% to 100%), which is comparable to the 91% (95% CI, 89% to 93%) 5-year survival of the IGCCCG GR patients. IGCCCG risk status (P =.005) and cluster affiliation (P =.04) were independent predictors of outcome with hazard ratios of 5.0 (95% CI, 1.6 to 15.4) and 4.6 (95% CI, 1.04 to 20.1), respectively. CONCLUSION: These results suggest that there is a subgroup of NSGCT patients with embryonal carcinoma (with or without other histologies) with a specific tumor biology profile (high Ki67, low apoptosis, and low p53) whose survival is better than that of the overall patient group. The unexpectedly good outcome for the prominent cluster and independent-risk status suggest that subgroups of GCT reflecting different abilities to respond to treatment exist within IGCCCG prognostic categories.

Apoptosis↗
PubMed2003

Group sequential design for comparative diagnostic accuracy studies.

In the field of diagnostic medicine, comparative clinical trials are necessary for assessing the utility of one diagnostic test over another. The area under the receiver operating characteristic (ROC) curve, commonly referred to as AUC, is a general measure of a test's inherent ability to distinguish between patients with and without a condition. Standardized AUC difference is the most frequently used statistic for comparing two diagnostic tests. In therapeutic comparative clinical trials with sequential patient entry, fixed sample design (FSD) is unjustified on ethical and economical grounds and group sequential design (GSD) is frequently used. In this paper, we argue that the same reasoning exists for the comparative clinical trials in diagnostic medicine and hence GSD should be utilized in this field for designing trials. Since computation of the stopping boundaries of GSD and data analysis after a group sequential test rely heavily on Brownian motion approximation, we derive the asymptotic distribution of the standardized AUC difference statistic and point out its resemblance to the Brownian motion. Boundary determination and sample size calculation are then illustrated through an example from a cancer clinical trial.

Area Under Curve↗
PubMed2003

Methods for categorizing a prognostic variable in a multivariable setting.

The literature is filled with examples of categorization of a continuous prognostic variable in a univariable setting followed by the addition of this categorical variable to an existing multivariable model. Typically, an "optimal" cutpoint for a new prognostic variable is obtained through a systematic search relating the variable to the outcome in an univariable manner. The corresponding categorical variable is then fitted in a multivariable model along with other already established prognostic covariates to assess the additional value of the new variable. This prompts the question whether the cutpoint search should have been performed in the same multivariable setting where it will ultimately be used. In this paper, we extend the univariable cutpoint search methods (split-sample approach and two-fold cross-validation approach) to the multivariable setting using -2 x log-likelihood statistic as the correlative measure. A Monte Carlo simulation study demonstrates that both methods are more efficient in detecting the true cutpoint and in estimating the effect size under the multivariable setting as opposed to the univariable setting. The cross-validation method performs better than the split-sample method in univariable as well as multivariable scenarios. For the cross-validation method in the multivariable setting, there is still a substantial loss of power when a cutpoint model is used in cases where there is a continuous relationship between the covariate and the outcome. An example is provided to illustrate the value of the multivariable cross-validation approach.

Humans↗
PubMed2003

A case-controlled study of 18-fluorodeoxyglucose positron emission tomography in the detection of pelvic recurrence in previously irradiated rectal cancer patients.

BACKGROUND: Although effective at detecting locally recurrent colorectal cancer, the accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for detecting rectal cancer recurrence in an irradiated pelvis has not been systematically studied. STUDY DESIGN: Records of surgically resected rectal cancer patients who underwent FDG-PET imaging at least 6 months after external beam radiation therapy (EBRT) were reviewed. Cases (n = 19) were defined as scans from patients in whom a pelvic recurrence was confirmed (histologically, n = 14, radiologic followup, n = 5). Controls (n = 41), defined as scans from patients without clinical or radiologic evidence of pelvic recurrence, were compared with cases for the time interval between completion of EBRT and FDG-PET imaging (RT/PET interval, mean 25.1 months versus 27.5 months, respectively), as well as EBRT dose (mean 5,084 cGy versus 5,062 cGy, respectively). All 60 FDG-PET scans were iteratively reconstructed and reinterpreted by a single nuclear medicine physician blinded to original FDG-PET interpretation and disease status. Certainty of disease was scored on a five-point scale (1 to 5), with scores greater than or equal to 4 considered positive. RESULTS: FDG-PET correctly identified 16 of 19 recurrences, for a sensitivity of 84% and specificity of 88%. Overall accuracy was 87%. Positive predictive value was 76% and negative predictive value was 92%. Positive predictive value and accuracy improved in scans performed more than 12 months after EBRT. CONCLUSIONS: Our preliminary data suggest that FDG-PET is an accurate modality for detecting pelvic recurrence of rectal cancer after full-dose EBRT. Its reliability appears to improve with time, perhaps because of resolution of early postradiation inflammation.

Case-Control Studies↗
PubMed2003

Phase II trial of ZD1839 (IRESSA) in patients with advanced renal cell carcinoma.

Eighteen patients with advanced renal cell carcinoma (RCC) were treated on a phase II trial with ZD1839 (IRESSA). Treatment efficacy was determined using the endpoint of improvement in time to progression (TTP) compared to TTP in patients who received interferon-alpha therapy. The Memorial Sloan Kettering Cancer Center database of renal cell patients shows that patients receiving therapy with interferon-alpha had a median TTP of 4.7 months, with 40% of patients having disease progression at 4 months. To show efficacy in this trial, 60% of evaluable patients would have to remain progression free at 4 months. Treatment with ZD1839 did not result in any complete or partial responses, and 13 patients (81%) had progression of disease within 4 months of start of therapy. At the dose and schedule used in this trial, the lack of antitumor activity associated with ZD1839 does not support further study in patients with metastatic RCC.

Adult↗
PubMed2002

Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder.

PURPOSE: The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg. RESULTS: Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology). CONCLUSION: Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.

Administration, Intravesical↗
PubMed2002

Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology.

PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma (RCC) with histology other than clear-cell type, including collecting duct (or medullary carcinoma), papillary, chromophobe, and unclassified histologies. PATIENTS AND METHODS: Sixty-four patients with metastatic non-clear-cell RCC histology were the subjects of this retrospective review. Included in the analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of 1,166 patients from a surgery database, and 23 of 357 patients from a pathology database. RESULTS: The prevalent histology was collecting duct, present in 26 (41%) patients. The number of patients with chromophobe and papillary histologies was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors that could not be classified for specific tumor histology. Among the 43 patients treated with 86 systemic therapies, including 37 cytokine therapies, two patients (5%) were observed to have a partial response. The median overall survival time was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer for patients with chromophobe tumors compared with collecting duct or papillary histology, and this group included four patients with survival of greater than 3 years. CONCLUSION: RCC consists of a heterogeneous group of tumors including clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types. Non-clear-cell histologies constitute less than 10% of patients in general populations of patients with advanced RCC treated on clinical trials. Metastatic non-clear-cell RCC is characterized by a resistance to systemic therapy and poor survival, with the survival for patients with chromophobe tumors longer than that for patients with metastatic collecting duct or papillary RCC. Treatment with novel agents on clinical trials is warranted.

Adolescent↗
PubMed2002

Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma.

PURPOSE: To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma (RCC) treated with interferon-alfa as initial systemic therapy. The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy. PATIENTS AND METHODS: Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospective clinical trials were the subjects of this retrospective analysis. Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model. RESULTS: The median overall survival time was 13 months. The median time to progression was 4.7 months. Five variables were used as risk factors for short survival: low Karnofsky performance status, high lactate dehydrogenase, low serum hemoglobin, high corrected serum calcium, and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year. Each patient was assigned to one of three risk groups: those with zero risk factors (favorable risk), those with one or two (intermediate risk), and those with three or more (poor risk). The median time to death of patients deemed favorable risk was 30 months. Median survival time in the intermediate-risk group was 14 months. In contrast, the poor-risk group had a median survival time of 5 months. CONCLUSION: Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations. The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm.

Adult↗
PubMed2002

Salvage chemotherapy for patients with advanced pure seminoma.

PURPOSE: We describe the response to conventional or high-dose salvage chemotherapy in patients with advanced seminoma who experience disease progression after receiving first-line platinum-based treatment. PATIENTS AND METHODS: Twenty-seven patients with progressive, advanced, pure seminoma were treated with salvage chemotherapy. Fifteen patients were treated with conventional-dose cisplatin-and-ifosfamide combination chemotherapy. Twelve patients were treated with high-dose chemotherapy followed by autologous stem-cell rescue. RESULTS: Fifteen patients (56%) achieved a complete response (CR), nine achieved CR with a conventional-dose cisplatin and ifosfamide program, and six experienced CR after high-dose chemotherapy. Fourteen patients (52%) are alive and disease-free, with 13 (48%) continuously disease-free at a median follow-up of 72 months. Twelve (57%) of 21 patients whose pretreatment tumors were studied morphologically were found to have seminoma with atypia. Eight patients underwent resection after salvage chemotherapy; six with histologic findings of necrotic debris/fibrosis alone are alive and disease-free at last follow-up. Both patients with viable seminoma found at surgery died of disease. CONCLUSION: Most patients with advanced seminoma are cured with standard first-line programs of cisplatin and etoposide with or without bleomycin. A small minority of patients with pure seminoma have resistant tumors and require salvage chemotherapy. In this setting, approximately 50% of patients with recurrent pure seminoma achieve durable CR with conventional or high-dose salvage chemotherapy. Identification of biologic markers to predict clinical outcome and an enhanced understanding of the basic biologic features of seminoma may lead to improvements in the management of this disease.

Adult↗
PubMed2002

Phase II trial of thalidomide for patients with advanced renal cell carcinoma.

PURPOSE: To assess efficacy and toxicity of thalidomide in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-six patients with RCC were treated with thalidomide at a starting dose of 200 mg daily. Thalidomide was increased by 200 mg every 2 weeks until a maximum dose of 800 mg or prohibitive toxicity was reached. Fifteen patients had prior nephrectomy, 11 patients had no prior systemic therapy, and 15 had received one prior systemic regimen. RESULTS: A maximum dose of 800 mg, 600 mg, 400 mg, and 200 mg was reached in five, 10, eight, and three patients, respectively. Grade 2 and 3 dyspnea occurred in four and three patients, respectively. Grade 2 and 3 neurologic toxicity was observed in five and two patients, respectively. Of the 25 assessable patients, the best response was stable disease in 16 (95% confidence interval [CI], 43% to 82%) patients. The 6-month progression-free survival rate was 32% (95% CI, 14% to 50%). Three patients achieved prolonged stable disease of 16, 16+, and 18+ months, including two patients who were refractory to previous cytokine therapy. Fifty-seven percent were alive at 1 year (95% CI, 37% to 76%). CONCLUSION: This trial does not support the routine use of thalidomide to induce partial response for metastatic RCC. Because disease stabilization occurs as a part of the natural history of metastatic RCC, the potential effect of thalidomide on progression-free and overall survival for patients with advanced RCC is being addressed in a randomized phase III trial. New immunomodulatory analogs of thalidomide that have shown potentially greater antitumor effects in preclinical models warrant study in metastatic RCC.

Adult↗
PubMed2002

Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy.

OBJECTIVE: To determine whether selected clinicopathologic factors, including the extent of pathologic response to preoperative radiation and chemotherapy (RT +/- chemo), have an impact on long-term recurrence-free survival (RFS) in patients with locally advanced primary rectal cancer after optimal multimodality therapy. SUMMARY BACKGROUND DATA: Although complete pathologic response to preoperative RT +/- chemo has been detected in up to 30% of rectal cancers, its significance on long-term outcome has not been widely reported. Previous retrospective studies evaluating clinical outcome in patients with complete or near-complete pathologic response documented good prognosis in this population but were limited by median follow-up in the range of 2 to 3 years. METHODS: Sixty-nine patients with locally advanced (T(3-4) and/or N1) primary rectal cancer were prospectively identified. All were treated at one institution with preoperative RT to the pelvis (at least 4,500 cGy). Forty patients received concurrent preoperative 5-fluorouracil-based chemotherapy and 27 received both pre- and postoperative chemotherapy. Patients underwent resection 4 to 7 weeks after completion of RT. TNM stage, angiolymphatic or perineural invasion, and extent of response to preoperative RT +/- chemo were determined by pathologic evaluation. Adverse pathologic features were defined as the presence of angiolymphatic and/or perineural invasion. RFS at 5 years was determined by the Kaplan-Meier method. RESULTS: With a median follow-up of 69 months, 5-year RFS was 79%. RFS was significantly worse for patients with aggressive pathologic features and positive nodal status identified in the postirradiated surgical specimen. Risk ratios for RFS were 3.68 for the presence of aggressive pathologic features and 4.64 for node-positive rectal cancers. In patients with greater than 95% rectal cancer response to preoperative RT +/- chemo, only one patient has died as a consequence of cancer, another has died of an unrelated cause, and the remainder were free of disease with a minimum follow-up of 47 months. CONCLUSIONS: These data suggest that a marked response to preoperative RT +/- chemo may be associated with good long-term outcome but was not predictive of RFS. The presence of poor histopathologic features and positive nodal status are the most important prognostic indicators after neoadjuvant therapy.

Adult↗
PubMed2002

Testicular seminoma: a clinicopathologic and immunohistochemical study of 105 cases with special reference to seminomas with atypical features.

In spite of the high curability rates, rare cases of testicular seminoma behave in an unexpectedly aggressive manner. No effective markers are currently available that can predict such uncommon behavior. We studied 105 cases of testicular seminoma on whom the primary resection was performed at the Memorial Sloan-Kettering Cancer Center, New York, to investigate any relationship between morphology, immunohistochemical features, and clinical/pathological stages. Fifty-nine percent of the cases presented with pT stage 1 and 74 percent with American Joint Committee on Cancer (AJCC) stage I. In univariate analysis, tumor size, mitotic count, and presence of necrosis showed significant associations with pT stage (p = 0.0001, 0.0001, and 0.04, respectively), and the presence of vascular invasion (p = 0.0001, 0.0001, and 0.02, respectively). In multivariate analysis, both the tumor size and mitotic counts were independent predictors of pT stage (p = 0.0004 and 0.0001) and vascular invasion (p = 0.0004 and 0.0001). When tumors were separated on the basis of architectural and/or cytological atypia into "usual seminomas" and "seminomas with atypia", these were significantly associated with AJCC stage (p = 0.02), and c-kit protein (p = 0.0005) and CD30 expression (p = 0.02). In addition, "seminomas with atypia" also tended to show a higher proliferation activity as judged by Ki67 reactivity (p = 0.06), as well as express the marker of epithelial differentiation, Cam 5.2 (p = 0.09). In summary, we find that the morphologic features in testicular seminomas are associated with factors of clinical relevance. Also, "seminomas with atypia" differ from "usual seminomas" morphologically, present at a higher AJCC stage, and possibly represent an early step in transformation of seminomas toward a more aggressive phenotype. While not proposing a new entity, we suggest that when these atypical features are encountered in an otherwise classical seminoma, investigations must be performed to exclude an early carcinomatous differentiation or even earlier changes toward such a differentiation, such as lack of c-kit protein expression.

Adult↗
PubMed1999

Tumor Treatment Response Based on Visual and Quantitative Changes in Global Tumor Glycolysis Using PET-FDG Imaging. The Visual Response Score and the Change in Total Lesion Glycolysis.

"Functional" tumor treatment response parameters have been developed to measure treatment induced biochemical changes in the entire tumor mass, using positron emission tomography (PET) and [F-18] fludeoxyglucose (FDG). These new parameters are intended to measure global changes in tumor glycolysis. The response parameters are determined by comparing the pre- and posttreatment PET-FDG images either visually from the change in image appearance in the region of the tumor, or quantitatively based on features of the calibrated digital PET image. The visually assessed parameters are expressed as a visual response score (VRS), or visual response index (VRI), as the estimated percent response of the tumor. Visual Response Score (VRS) is recorded on a 5 point response scale (0-4): 0: no response or progression; 1: 1-33%; 2: >33%-66%; 3: >66%-99%; and 4: >99%, estimated response, respectively. The quantitative changes are expressed as total lesion glycolysis TLG or as the change in TLG during treatment, also called deltaTLG or Larson-Ginsberg Index (LGI), expressed as percent response. The volume of the lesion is determined from the PET-FDG images by an adaptive thresholding technique. This response index is computed as, deltaTLG (LGI) = {[(SUV(ave))(1) * (Vol)(1) - (SUV(ave))(2) * (Vol)(2)]/[(SUV(ave))(1) * (Vol)(1)]} * 100. Where "1" and "2" denote the pre- and posttreatment PET-FDG, scans respectively. Pre- and posttreatment PET-FDG scans were performed on a group of 41 locally advanced lung (2), rectal (17), esophageal (16) and gastric (6) cancers. These patients were treated before surgery with neoadjuvant chemo-radiation. Four experienced PET readers determined individual VRS and VRI blinded to each other as well as to the clinical history. Consensus VRS was obtained based on a discussion. The interobserver variability captured by intraclass correlation coefficient was 89.7%. In addition, reader reliability was assessed for the categorized VRS using Kendall's coefficient of concordance for ordinal data and was found to be equal to 85% This provided assurance that these response parameters were highly reproducible. The correlation of deltaTLG with % change in SUV(ave) and % change in SUV(max), as widely used parameters of response, were 0.73 and 0.78 (P <.0001) respectively. The corresponding correlation of VRI were 0.63 and 0.64 (P <.0001) respectively. Both deltaTLG and VRI showed greater mean changes than SUV maximum or average (59.7% and 76% vs. 46.9% and 46.8%). We conclude that VRS and deltaTLG are substantially correlated with other response parameters and are highly reproducible. As global measures of metabolic response, VRS, VRI and deltaTLG (LGI) should provide complementary information to more commonly used PET response parameters like the metabolic rate of FDG (MRFDG), or the standardized uptake value (SUV), that are calculated as normalized per gram of tumor. These findings set the stage for validation studies of the VRS and deltaTLG as objective measures of clinical treatment response, through comparison to the appropriate gold standards of posttreatment histopathology, recurrence free survival, and disease specific survival in well characterized populations of patients with locally advanced cancers.

Journal Article↗
PubMed1999

FDG-PET in Esophageal Cancer. Incremental Value over Computed Tomography.

OBJECTIVES: To evaluate the clinical utility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with cancer (CA) of the esophagus, and its incremental value over computed tomography (CT) scan.METHODS: Positron emission tomography (PET) scan and CT scan reports of all patients with biopsy-proven CA esophagus from December 1995 to August 1998 were reviewed. PET images were acquired on a high-resolution dedicated PET scanner 45 minutes to 1 hour after intravenous injection of 370 MBq of fluorine-18-fluorodeoxyglucose (F-18-FDG). Emission images of the neck, chest, and abdomen were obtained, followed by transmission scans at selected sites.RESULTS: One hundred fifty-one scans were performed on 109 patients. The clinical indications were staging (67), follow-up evaluation after chemoradiation (66), and evaluation of possible recurrence after surgery (18). A final diagnosis was reached in 99 patients at 276 sites by histology (91.3%) or clinical follow-up of over 6 months (8.7%). FDG-PET scan showed a sensitivity of 80%, specificity of 95%, and accuracy of 86% compared with 68%, 81%, and 73% for CT. Of the 32 false negatives, 23 were perigastric or paraesophageal lymph nodes close to the primary, and 5 were peritoneal or pleural spread. PET detected 99% of the primary lesion (66 out of 67) with a mean standardized uptake value (SUV) of 11 (3.6 to 46). There was no apparent difference in 18F-fluorodeoxyglucose (FDG) uptake between squamous cell CA (N = 15, mean SUV 10.5), adenoCA (N = 48, mean SUV 11.2), and other cell types (N = 3, mean SUV 10.3). The one case where PET missed the primary lesion turned out to have a lesion measuring 0.4 cm in its maximum diameter. In 20 patients out of the 99 with confirmed diagnosis (20%), PET detected 24 confirmed lesions not seen on CT, and in 14 patients (14%) management was changed as a result of the PET finding.CONCLUSION: FDG-PET scan is more accurate than CT (86% vs. 73%; P = 0.0002) in the evaluation of patients with CA esophagus. It provides additional information over CT, impacting on management in 14% of patients.

Journal Article↗