F.M. Kong

Radiation therapy for epidermoid carcinoma of the anal canal, clinical and treatment factors associated with outcome.

BACKGROUND AND PURPOSEnIn recent years, treatment with combined chemotherapy and radiation has become the standard of care for epidermoid carcinoma of the anus. However, optimal radiotherapy techniques and doses are not well established.nnnMATERIALS AND METHODSnDuring the period 1975-1997, 106 patients with epidermoid carcinoma of the anal canal underwent radiation therapy. Treatment policies evolved from radiation therapy alone or with surgery, to combined chemotherapy and radiation followed by surgery, to combined chemotherapy and radiation.nnnRESULTSnOverall 74% of patients were NED (no evidence of disease) at last follow-up. The most important clinical correlate with ultimate freedom from disease (includes the contribution of salvage surgery) was extent of disease. The 5-year ultimate freedom from disease was 87+/-5% for T1/T2N0, 78+/-10% for T3N0 (15% salvaged by surgery), and 43+/-10% for either T4N0 or any N+ lesions (P<0.001, Tarone-Ware). There was no difference between planned vs. expectant surgery (5-year ultimate NED: 67+/-11% planned surgery vs. 73+/-5% expectant surgery). The most important correlate with late toxicity was a history of major pelvic surgery (surgical vs. non-surgical group: P=0.013, Fishers exact test, two-tailed summation). Thirty-three additional malignancies have been seen in 26 patients. The most common additional malignancies were gynecologic (nine cases), head and neck (six cases), and lung cancer (five cases).nnnCONCLUSIONSnFor T1/T2N0 disease, moderate doses of radiation combined with chemotherapy provided adequate treatment. T4N0 and N+ lesions are the most appropriate candidates for investigational protocols evaluating dose intensification. T3N0 tumors may also be appropriate for investigation; however, dose intensification may ultimately prove counterproductive if the cure rate is not improved and salvage surgery is rendered more difficult. The volume of irradiated small bowel should be minimized for patients who have a past history of major pelvic surgery or who (because of locally advanced tumors) may need salvage surgery in the future. Because of the occurrence of additional malignancy, patients with anal cancer should receive general oncologic screening in long-term follow-up.

Factors associated with overall survival in 1706 patients with nasopharyngeal carcinoma: Significance of intensive neoadjuvant chemotherapy and radiation break

BACKGROUND AND PURPOSEnTo exam factors associated with overall survival (OS) in patients with nasopharyngeal carcinoma (NPC).nnnMATERIALS AND METHODSnThis study is a retrospective study of a total of 1706 consecutive NPC patients from a single institution between January 1995 and December 1998. One thousand eighty-one patients were treated with radiotherapy (RT) alone and 625 with an intensive course of neoadjuvant chemotherapy followed by RT. Patient, tumor and treatment factors were analyzed for their significance on 5-year overall survival (OS).nnnRESULTSnYounger age, female gender, absence of anemia pre-RT, early tumor stage, interruption of RT, and neoadjuvant chemotherapy were significantly associated with survival under multivariate analysis (all P<0.05). The 5-year OS rates were 100%, 75.9% (95%CI 71.6-80.2%), 66.5% (95%CI 62.8-70.2%), and 49.3% (95%CI 45.0-53.6%) for stage I, II, III, and IV (P<0.05); 68.9% (95%CI 66.2-71.5%) and 63.7% (95%CI 61.5-65.8%), for patients treated with or without neoadjuvant chemotherapy (P=0.0051), and 51.7% (95%CI 45.0-58.4%) and 69.5% (95%CI 67.2-71.7%) for patients with or without treatment break (P<0.0001), respectively.nnnCONCLUSIONnIntensive neoadjuvant chemotherapy and absence of radiation break seem to be favorable factors associated with long-term survival in patients with NPC.

NONINVASIVE EVALUATION OF MICROSCOPIC TUMOR EXTENSIONS USING STANDARDIZED UPTAKE VALUE AND METABOLIC TUMOR VOLUME IN NON-SMALL-CELL LUNG CANCER

PURPOSEnTo prospectively evaluate whether maximal microscopic extensions (MEmax) correlate with maximal standardized uptake value (SUVmax) and metabolic tumor volume (MTV) at 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images in non-small-cell lung cancer (NSCLC).nnnMETHODS AND MATERIALSnThirty-nine patients with Stage I-IIIA NSCLC underwent surgery after FDG-PET/CT scanning. SUVmax and MTV were calculated on the PET/CT images. The maximum linear distance from the tumor margin to the farthest extent of the tumor in every dimension was measured at the tumor section. The correlations among MEmax, SUVmax, MTV and other clinical pathologic parameters were analyzed.nnnRESULTSnMEmax for all patients had a significant correlation with SUVmax (r = 0.777, p = 0.008) and MTV (r = 0.724, p < 0.001). When expressed in terms of the probability of covering ME with respect to a given margin, we suggested that margins of 1.93 mm, 3.90 mm, and 9.60 mm for SUVmax ≤ 5, 5-10, and >10 added to the gross tumor volume would be adequate to cover 95% of ME.nnnCONCLUSIONSnThis study demonstrated that tumors with high SUVmax and MTV have more MEmax and would therefore require more margin expansion from gross tumor volume to clinical target volume. FDG-PET/CT, especially for SUVmax, is promising and effective and merits additional study in noninvasive delimiting of the clinical target volume margin for NSCLC.

Utilize target motion to cover clinical target volume (ctv) – a novel and practical treatment planning approach to manage respiratory motion

PURPOSEnTo use probability density function (PDF) to model motion effects and incorporate this information into treatment planning for lung cancers.nnnMATERIAL AND METHODSnPDFs were calculated from the respiratory motion traces of 10 patients. Motion effects were evaluated by convolving static dose distributions with various PDFs. Based on a differential dose prescription with relatively lower dose to the clinical target volume (CTV) than to the gross tumor volume (GTV), two approaches were proposed to incorporate PDFs into treatment planning. The first approach uses the GTV-based internal target volume (ITV) as the planning target volume (PTV) to ensure full dose to the GTV, and utilizes the motion-induced dose gradient to cover the CTV. The second approach employs an inhomogeneous static dose distribution within a minimized PTV to best match the prescription dose gradient.nnnRESULTSnMotion effects on dose distributions were minimal in the anterior-posterior (AP) and lateral directions: a 10-mm motion only induced about 3% of dose reduction in the peripheral target region. The motion effect was remarkable in the cranial-caudal direction. It varied with the motion amplitude, but tended to be similar for various respiratory patterns. For the first approach, a 10-15 mm motion would adequately cover the CTV (presumed to be 60-70% of the GTV dose) without employing the CTV in planning. For motions < 10-mm, an additional PTV with a margin inversely related to the motion was needed to cover the CTV. The second approach was used for motions > 15-mm. An example of inhomogeneous static dose distribution in a reduced PTV was given, and it showed significant dose reduction in the normal tissue without compromising target coverage.nnnCONCLUSIONSnRespiratory motion-induced dose gradient can be utilized to cover the CTV and minimize the lung dose without the need for more sophisticated technologies.

Quality of life following 3D conformal radiation therapy or permanent interstitial brachytherapy for localized prostate cancer

Abstract Purpose: Both 3D Conformal Radiation Therapy (3DCRT) and Transperineal Interstitial Permanent Brachytherapy (TIPPB) are offered as suitable non-surgical alternatives to radical prostatectomy. Despite equivalent cancer control, very little data has been published that compares Quality of Life (QOL) in contemporary cohorts of patients choosing these treatments. Materials and Methods: Since 1998, patients selecting either 3DCRT alone or TIPPB (monotherapy or boost after external beam) for primary management of localized prostate cancer were asked to participate in a prospective assessment of QOL measures. In this preliminary report, 41 3DCRT and 40 TIPPB (34 monotherapy, 6 boost) patients completed validated QOL instruments at each followup visit. QOL instruments included the International Prostate Symptom Score (IPSS), FACT-P, and Sexual Adjustment Questionnaire (SAQ). Results: The average age of men in each group was 69 years. Choice of treatment was left to the patient unless there were significant medical or technical contraindications to either modality. 3DCRT total doses ranged from 61-78 Gy (mean 73.5Gy) and TIPPB doses were 145Gy (TG43) in 34 I-125 implants and 115 Gy in 1 Pd-103 (monotherapy) or 90 Gy in 5 Pd-103 (boost) implants. Patients undergoing TIPPB reported significantly worse urinary and sexual function than their counterparts receiving 3DCRT. The mean cumulative IPSS was 12.5 with TIPPB compared to 8.3 with 3DCRT (p=0.036). Differences were most pronounced in the first 12 months after treatment, particularly with respect to the strength of stream and the need to strain. TIPPB patients were more likely to report a need to urinate frequently (p=0.02), require a pad (p=0.001), be bothered (p=0.02), or have activity limited by urinary side effects (p=0.01). TIPPB patients were less likely to resume sexual activity within 6 months after treatment (p=0.0003) and engaged in sexual activity less often (p= 0.016) than 3DCRT patients. They were also more likely to express dissatisfaction with sex (p=0.009) and less willing to initiate sexual activity (p=0.02). TIPPB patients also reported a small, but significant increase frequency of trouble moving their bowels (p=0.018), and lack of energy (p=0.05). When differences occurred between the two groups, they were most dramatic in the first 6 to 9 months with some differences persisting for more than one year. Conclusion: Although both treatments are effective in the management of early stage prostate cancer, patients undergoing TIPPB have significantly more urinary, sexual, and bowel troubles than similar patients treated with 3DCRT.

TU-AB-202-07: A Novel Method for Registration of Mid-Treatment PET/CT Images Under Conditions of Tumor Regression for Patients with Locally Advanced Lung Cancers

PURPOSEnIn PET-guided adaptive radiotherapy (RT), changes in the metabolic activity at individual voxels cannot be derived until the duringtreatment CT images are appropriately registered to pre-treatment CT images. However, deformable image registration (DIR) usually does not preserve tumor volume. This may induce errors when comparing to the target. The aim of this study was to develop a DIR-integrated mechanical modeling technique to track radiation-induced metabolic changes on PET images.nnnMETHODSnThree patients with non-small cell lung cancer (NSCLC) were treated with adaptive radiotherapy under RTOG 1106. Two PET/CT image sets were acquired 2 weeks before RT and 18 fractions after the start of treatment. DIR was performed to register the during-RT CT to the pre-RT CT using a B-spline algorithm and the resultant displacements in the region of tumor were remodeled using a hybrid finite element method (FEM). Gross tumor volume (GTV) was delineated on the during-RT PET/CT image sets and deformed using the 3D deformation vector fields generated by the CT-based registrations. Metabolic tumor volume (MTV) was calculated using the pre- and during-RT image set. The quality of the PET mapping was evaluated based on the constancy of the mapped MTV and landmark comparison.nnnRESULTSnThe B-spline-based registrations changed MTVs by 7.3%, 4.6% and -5.9% for the 3 patients and the correspondent changes for the hybrid FEM method -2.9%, 1% and 6.3%, respectively. Landmark comparisons were used to evaluate the Rigid, B-Spline, and hybrid FEM registrations with the mean errors of 10.1 ± 1.6 mm, 4.4 ± 0.4 mm, and 3.6 ± 0.4 mm for three patients. The hybrid FEM method outperforms the B-Spline-only registration for patients with tumor regression CONCLUSION: The hybrid FEM modeling technique improves the B-Spline registrations in tumor regions. This technique may help compare metabolic activities between two PET/CT images with regressing tumors. The author gratefully acknowledges the financial support from the National Institutes of Health Grant.

TH‐E‐230A‐06: Comparison of Correction and Model Based Dose Algorithms in Lung Cancer Retrospective Dose Recalculation and Treatment Outcome Evaluation

Purpose: To perform a systematic comparison of the Monte Carlo(MC), convolution/superposition (CS), and equivalent path length (EPL)‐based dose calculation algorithms for the purposes of outcomes modeling in lungcancertreatment planning.Methods: Several treatment plans (originally planned using EPL) from a large database of patients treated on a lungdose escalation protocol were retrospectively recalculated using MC and CS. Doses were computed in the homogeneous (unit‐density) and heterogeneous geometries; homogeneous calculations were used to elicit differences in the beam models To evaluate algorithmic differences due to heterogeneity effects, beam model differences were minimized by adjusting beam weights in the homogeneous plans to achieve the same prescribed dose with each algorithm. These beam weights were then applied to the heterogeneous geometries. Absolute dose distributions were compared using: color‐wash dose difference displays, isodose lines, EUD (for the target) and mean lungdose (MLD) and NTCP (for the normal lungs).Results: For the target, MC and CS‐computed EUDs were in good agreement for both homogeneous and heterogeneous cases, with maximum dose differences of 1.2 Gy noted. Differences between EPL and MC (or CS) were generally much larger, in the heterogeneous plans extending up to 6 Gy. Differences in MLD computed with MC and CS ranged between 2% and 15% in the heterogeneous plans. These differences were similar in the corresponding homogeneous geometries, illustrating the importance of beam model disparities. For EPL, differences in the MLD and NTCP (relative to MC or CS) were much larger in the heterogeneous plans indicating systematic differences in the normal lungdose prediction. Conclusion: Evidence thus far is suggestive that discrepancies in dose computed with EPL and MC (or CS) will lead to differences in correlations of dose with outcome with respect to the target as well as normal tissue complications (radiation induced pneumonitis) and calculated NTCP.