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The correlation between tumor volume and clonogen number: evidence for a linear relationship in advanced squamous cell carcinoma of the head and neck
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Radiation Oncology, Biology, Physics
Volume 30, Supplement 1
85 THE CORRELATION BETWEEN TUMOR VOLUME AND CLONOGEN NUMBER: EVIDENCE FOR A LINEAR RELATIONSHIP IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK Christopher R. Johnson, M.D., Howard D. Thames, Ph.D.^, David T. Huang, M.D., Ph.D., Rupert K. Schmidt-Ullrich, M.D. Department of Radiation Oncology, Medical College of Virginia, Richmond, Virginia 23298 *Department of Biomathematics, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030
Purpose/Objective: The relationship between clonogen number and tumor volume remains a controversial subject with proponents supporting both linear and nonlinear correlations. In addition, supporting clinical data is sparse and uses imprecise volumetric techniques. This study utilizes statistical modeling and precise CT derived tumor volume measurements in patients with advanced head and neck cancer. A mixture model will be utilized to fit clinical data to the equation describing the relationship: m = a Vb where m is the mean number of surviving clonogens, a is a proportionality constant, V is tumor volume and b is the volume exponent. Theoretically, parameter b should be 1 if there is a linear relationship. However, one previous clinical study determined this value to be 0.24. ??
Materials and Methods: Local tumor control was reviewed in a series of 51 head and neck cancer patients consistently managed with a concomitant boost accelerated superfractionated radiotherapy schedule. Tumor volume estimates were determined from serial reconstruction of pre-treatment CT scans using a volume integration technique. Volumes of primary tumor, lymph node disease and total tumor (primary + lymph node volume) were derived. Tumor volume parameters and failure time were entered into a mixture model using a log-logistic failure time distribution. The parameters a and b were estimated from the model fit. Results: The total tumor volume range is 5-196 cm3, the primary tumor volume range is 3-196 cm3 and lymph node disease volume range is O-76 cm3. Actuarial local-regional control at 36 months is 63%. Univariate and multivariate analyses demonstrate that total tumor volume is the most significant predictive parameter for local-regional control of the tested variables (T-stage, N-stage, total tumor volume, primary site, sex, age). With total tumor volume incorporated into the mixture model, the derived value of b is 2.7 (confidence interval: -.17 to 5.6). Similar analysis with primary tumor volume derived the value b as 1.54 (confidence interval: .37 to 2.71). Conclusion: This study demonstrates the importance of tumor volume as a parameter predicting local-regional disease control in advanced head and neck cancer managed with radiotherapy. More precise volume measurements and more consistent radiotherapy technique distinguish this study from previous ones. Although the confidence intervals are wide, the derived values of b are higher than previously reported and strongly suggest a closer relationship between clonogen number and tumor volume than has been reported. Tumor volume measurements are clinically important as they correlate with clonogen number. The implications of such data will be discussed with respect to altered fractionation schedules.
86 NASOPHARYNGEAL CARCINOMA: EVALUATION OF N-STAGING BY HO AND AJCC/uICC SYSTEM l~ee, A.W. M.; Foo, W.; lChan, D. K. K Radiotherapy and Oncology Departments of Queen Elizabeth Hospital, andlpamela Youde Nethersole Eastern Hospital, Hong Kong.
Purpose: To evaluate the prognostic accuracy of the N-staging system by Ho and AJCCLJICC Materials & Methods: Five thousand and twenty patients with undifferentiated or poorly differentiated squamous ceil carcinoma of the nasopharynx treated at the Queen Elizabeth Hospital during the years 1976-1985 were analysed. They were initially staged with the Ho’s system, but detailed records of the extent of cancer involvement allowed accurate retrospective re-staging with AJCCXJICC (1988) system. Assessment of nodal extent depended almost entirely on palpation, only 14% had additional investigation with computed tomography. To evaluate the independent prognostic significance of N-stages as defined by the two systems, T-stage adjusted analyses of the 4730 patients presenting without distant metastasis were performed. Results: N-stage by both systems showed strongly significant overall trend of correlation with subsequent distant metastasis and cancer-deaths @ value < O.OOOl),but no correlation with local failure (p value > 0.0529). Interpretation on prediction of regional failure was complicated by the fact that prophylactic neck irradiation was withheld in 70% of the NO patients, but strongly significant trend was demonstrated as the N-stage increased from Nl to N3 0, value < 0.0001) Howevei, closer scrutiny revealed that within each level as defined by Ho’s system, addition of nodal size, multiplicity and bilaterality could tiuther improve prognostic accuracy. Within each AJCCXJICC N-stage, those with low level involvement had significantly higher incidence of failures, but the difference between upper and mid level did not reach statistical significance. There was also no justification in differentiating between ipsilateral and contralateral involvement. Conclusion: The present data hence suggest that the basic concept of AJCCiUICC system should be adopted, but supraclavicular extension should be incorporated as a staging parameter, and contralateral involvement be given the same weighting as ipsilateral counterpart.
Radiation Oncology, Biology, Physics
Volume 30, Supplement 1
85 THE CORRELATION BETWEEN TUMOR VOLUME AND CLONOGEN NUMBER: EVIDENCE FOR A LINEAR RELATIONSHIP IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK Christopher R. Johnson, M.D., Howard D. Thames, Ph.D.^, David T. Huang, M.D., Ph.D., Rupert K. Schmidt-Ullrich, M.D. Department of Radiation Oncology, Medical College of Virginia, Richmond, Virginia 23298 *Department of Biomathematics, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030
Purpose/Objective: The relationship between clonogen number and tumor volume remains a controversial subject with proponents supporting both linear and nonlinear correlations. In addition, supporting clinical data is sparse and uses imprecise volumetric techniques. This study utilizes statistical modeling and precise CT derived tumor volume measurements in patients with advanced head and neck cancer. A mixture model will be utilized to fit clinical data to the equation describing the relationship: m = a Vb where m is the mean number of surviving clonogens, a is a proportionality constant, V is tumor volume and b is the volume exponent. Theoretically, parameter b should be 1 if there is a linear relationship. However, one previous clinical study determined this value to be 0.24. ??
Materials and Methods: Local tumor control was reviewed in a series of 51 head and neck cancer patients consistently managed with a concomitant boost accelerated superfractionated radiotherapy schedule. Tumor volume estimates were determined from serial reconstruction of pre-treatment CT scans using a volume integration technique. Volumes of primary tumor, lymph node disease and total tumor (primary + lymph node volume) were derived. Tumor volume parameters and failure time were entered into a mixture model using a log-logistic failure time distribution. The parameters a and b were estimated from the model fit. Results: The total tumor volume range is 5-196 cm3, the primary tumor volume range is 3-196 cm3 and lymph node disease volume range is O-76 cm3. Actuarial local-regional control at 36 months is 63%. Univariate and multivariate analyses demonstrate that total tumor volume is the most significant predictive parameter for local-regional control of the tested variables (T-stage, N-stage, total tumor volume, primary site, sex, age). With total tumor volume incorporated into the mixture model, the derived value of b is 2.7 (confidence interval: -.17 to 5.6). Similar analysis with primary tumor volume derived the value b as 1.54 (confidence interval: .37 to 2.71). Conclusion: This study demonstrates the importance of tumor volume as a parameter predicting local-regional disease control in advanced head and neck cancer managed with radiotherapy. More precise volume measurements and more consistent radiotherapy technique distinguish this study from previous ones. Although the confidence intervals are wide, the derived values of b are higher than previously reported and strongly suggest a closer relationship between clonogen number and tumor volume than has been reported. Tumor volume measurements are clinically important as they correlate with clonogen number. The implications of such data will be discussed with respect to altered fractionation schedules.
86 NASOPHARYNGEAL CARCINOMA: EVALUATION OF N-STAGING BY HO AND AJCC/uICC SYSTEM l~ee, A.W. M.; Foo, W.; lChan, D. K. K Radiotherapy and Oncology Departments of Queen Elizabeth Hospital, andlpamela Youde Nethersole Eastern Hospital, Hong Kong.
Purpose: To evaluate the prognostic accuracy of the N-staging system by Ho and AJCCLJICC Materials & Methods: Five thousand and twenty patients with undifferentiated or poorly differentiated squamous ceil carcinoma of the nasopharynx treated at the Queen Elizabeth Hospital during the years 1976-1985 were analysed. They were initially staged with the Ho’s system, but detailed records of the extent of cancer involvement allowed accurate retrospective re-staging with AJCCXJICC (1988) system. Assessment of nodal extent depended almost entirely on palpation, only 14% had additional investigation with computed tomography. To evaluate the independent prognostic significance of N-stages as defined by the two systems, T-stage adjusted analyses of the 4730 patients presenting without distant metastasis were performed. Results: N-stage by both systems showed strongly significant overall trend of correlation with subsequent distant metastasis and cancer-deaths @ value < O.OOOl),but no correlation with local failure (p value > 0.0529). Interpretation on prediction of regional failure was complicated by the fact that prophylactic neck irradiation was withheld in 70% of the NO patients, but strongly significant trend was demonstrated as the N-stage increased from Nl to N3 0, value < 0.0001) Howevei, closer scrutiny revealed that within each level as defined by Ho’s system, addition of nodal size, multiplicity and bilaterality could tiuther improve prognostic accuracy. Within each AJCCXJICC N-stage, those with low level involvement had significantly higher incidence of failures, but the difference between upper and mid level did not reach statistical significance. There was also no justification in differentiating between ipsilateral and contralateral involvement. Conclusion: The present data hence suggest that the basic concept of AJCCiUICC system should be adopted, but supraclavicular extension should be incorporated as a staging parameter, and contralateral involvement be given the same weighting as ipsilateral counterpart.