Postoperative pulmonary complications following preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram

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I. J. Radiation Oncology

● Biology ● Physics

Volume 54, Number 2, Supplement, 2002

esophagitis 4%, and Taxol anaphylaxis 4%. Forty-two of 46 pts were subjected to surgery and complete resection was performed in 40 pts. Median follow-up times were 38 months (m) for all pts and 66 m for survivors only. Treatment related mortality was 8.7% (4/46 pts): 4.3% (2/46) from induction therapy and 4.7% (2/42) of surgery. Major histopathologic tumor response was noted in 58% (23/40) of pts: Pathologic complete response (pCR) in 43% (17/40) and microscopic residual disease (mRD) in additional 15% (6/40). Local tumor control was maintained in 95% of pts with pCR and mRD compared with 56% of pts with gross residual tumor (GRT) at 40 m (p⫽0.023). The rate of freedom from distant metastasis was 63% for pts with pCR and mRD compared with 18% for pts with GRT at 60 m (p⫽0.027). The overall survival rate was 52% for pts with pCR and mRD compared with 29% for pts with GRT at 60 m (p⫽0.123). The disease-free survival rate was 48% for pts with pCR and mRD compared with 12% for pts with GRT at 52 m (p⫽0.050). Conclusions: Sustained local tumor control may improve disease-free survival, and overall survival in esophageal cancer. BID RT for intensifying RT and exploiting chemo-radiation interaction in concurrent CT-RT deserves further study.

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The SORTIE Trial: Palliation with Stent (S) or Radiation Therapy (RT) 20 Gy in 5 Fractions Intervention for Esophageal Cancer Dysphagia: A Multicenter Trial for T-4, Mⴙ/- Squamous or Adenocarcinoma of the Esophagus. A Randomized Trial Relief from Dysphagia and Quality of Life (QOL) Analysis

A.T. Turrisi1, R.H. Hawes1, Y. Palesch1, C. Redmond2, T. Williams1, C. Reed1, P. Mauldin1, P.B. Cotton1 1 Medical University of South Carolina, Charleston, SC, 2University of Pittsburgh, Pittsburgh, PA Purpose/Objective: SORTIE, multicenter, randomized trial tests Ultraflex威 *stent versus high fraction external beam radiotherapy for palliation of dysphagia for patients with locally advanced, non-resectable esophageal cancer. A secondary goal compared Quality of Life. Materials/Methods: The primary analysis measured time to first occurrence of recurrent dysphagia, or failure of the randomly allocated intervention (S vs. RT: 20 Gy 5 Fx–repeat in 3 weeks, total dose 40Gy in 10 fractions) leading to crossover, or death. QOL was assessed at baseline and monthly intrevals by self-administered instruments: 1) EORTC QLQ-C30 esophageal cancer module and 2) the DDQ-15 Plus (our instrument). Results: 32 patients accrued overtwo years: median survival in the stent group was 101 days (95% CI46-127 days) and for the radiotherapy group median survival time was 141 days (95% CI88-209 days). There was a longer, non-significant median dysphagia-free survival in patients receiving the stent (32 versus 4 days). Seven patients died in the radiation therapy group before achieving satisfactory dysphagia improvement. However, the 75th percentile was longer in the radiotherapy group than for the stent group (336 versus 74 days). Survival analysis indicates that four radiotherapy patients survived more than 300 days: three alive at the end of the study period. Of those with stents, only one patient was alive at 229 days. Stricture and esophagitis were more common with radiotherapy treatment and bleeding, tumor in-growth more common with stent. Although not statistically significant, slight differences in QOL generally favored patients who received radiotherapy. Crossover was tolerable and without due hazard. Conclusions: Although requiring confirmation with larger patient numbers, results suggest the possibility that, while more immediate relief of dysphagia is obtained in patients with esophageal stents, overall disease palliation seems to be improved by radiation. The combination of stent and radiotherapy requires further analysis for optimal palliation. (*Ultraflex威; manufactured and study supported by Boston Scientific)

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Postoperative Pulmonary Complications Following Preoperative Chemoradiation for Esophageal Carcinoma: Correlation with Pulmonary Dose-Volume Histogram

H.K. Lee1, A.A. Vaporciyan2, J.D. Cox1, J.B. Putnam2, J.A. Ajani3, Z. Liao1, S.G. Swisher2, J.A. Roth2, R.W. Smythe2, G.L. Walsh2, R. Mohan1, R. Komaki1 1 Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, TX, 2Departments of Thoracic and Cardiovascular Surgery, M. D. Anderson Cancer Center, Houston, TX, 3Departments of Gastrointestinal Oncology and Digestive Diseases, M. D. Anderson Cancer Center, Houston, TX Purpose/Objective: To test the hypothesis that increased volumes of lung receiving low radiation doses may lead to significant pulmonary complications when using concurrent chemotherapy for preoperative esophageal carcinoma. Materials/Methods: A cohort of 111 patients who underwent preoperative chemoradiation was prospectively analyzed for pulmonary morbidity from 1998 to 2001. Pneumonia and acute respiratory distress syndrome were used as clinical endpoints for pulmonary complications as defined by the Centers for Disease Control and the American and European Consensus Conference Guidelines. In 55 patients, the pulmonary dose-volume histogram (DVH) was available for analysis and comprised this study cohort. All patients received concurrent chemotherapy with either 5-FU ⫹ Cisplatin, 5-FU ⫹ Taxol, 5-FU ⫹ Taxol ⫹ CPT-11, or 5-FU ⫹ Carboplatin. Thirty-seven patients received induction chemotherapy prior to concurrent chemoradiation. The median age was 62 years and the median radiotherapy dose was 45 Gy. The V10 (% volume receiving 10 Gy), V15, and V20 of the entire lung was recorded for each pulmonary DVH. Results: Nine (16%) of 55 patients had pulmonary complications, and two patients died secondary to progression of their pneumonia. A statistically significant increase in the rates of pulmonary complications were observed (37.5% vs. 7.7%, p ⫽ 0.013) when the volume receiving 10 Gy was ⱖ 40% vs. ⬍ 40%, respectively. A higher rate of complications was observed (50.0% vs. 10.6%, p ⫽ 0.019) when the volume receiving 15 Gy was ⱖ 35% vs. ⬍ 35%. Statistically significant difference in the rates of pulmonary complications (50% vs. 12.2%, p ⫽ 0.049) were observed at V20 ⱖ 30% vs. ⬍ 30%. The type of surgical procedure, the individual surgeon, the use of induction chemotherapy, the use of Taxol-based chemotherapy, or the presence of smoking history did not significantly correlate with pulmonary complications.

Proceedings of the 44th Annual ASTRO Meeting

Conclusions: Clinically significant postoperative pulmonary complications following preoperative chemoradiation were observed when increased volumes of lung received low radiation doses. These data suggest that with concurrent chemotherapy, radiotherapy techniques that may increase the volume of lung receiving low radiation doses may not negate the risk of significant pulmonary complications.

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Results of Definitive Irradiation in a Series of 305 Epidermoid Carcinomas of the Anal Canal

D. Elisabeth1, T. Emmanuel1, T. Emmanuel2, S. Alain3, G. Denis4, H. Sidney5, P. Rolland2, H. Rong1, P. Franc¸ oise1, S. Michel1 1 Department of Radiation Oncology, Tenon Hospital A.P.-H.P., Paris, France, 2Department of Surgery, St-Antoine Hospital A.P.-H.P., Paris, France, 3Department of Surgery, Diaconesses Hospital, Paris, France, 4Department of Surgery, Bichat Hospital A.P.-H.P., Paris, France, 5Department of Surgery, Tenon Hospital A.P.-H.P., Paris, France Purpose/Objective: To evaluate our data concerning locoregional control, late severe complications, sphincter conservation, and survival in a series of epidermoid cancer of the anal canal. Materials/Methods: Between June 1972 and January 1997, 305 patients (pts) without evident metastasis were treated with curative-intent radiation therapy (RT). The mean age was 65.5 years, with a male-to-female ratio of 0.15. The T-stages according to the 1987 UICC Classification were: 26 T1, 141 T2, 104 T3 and 34 T4. They were 49 pts with nodal involvement at presentation. The treatment started with external beam RT (EBRT) in 303 pts (median dose: 45 Gy). After a rest period of 4 to 6 weeks, a boost of 20 Gy was delivered by EBRT in 279 pts and by interstitial 192Ir brachytherapy (Bcy) in 17 pts. Seven pts received only one course of EBRT (mean dose: 49.5 Gy) and 2 pts were treated with interstitial 192Ir Bcy alone (55 Gy and 60 Gy, respectively). Concomitant chemotherapy (5-fluorouracil and either mitomycin C or cisplatin) was delivered to 19 pts. Mean follow-up was 103 months. Results: At the end of RT complete local tumor response rate was: 96% for T1, 87% for T2, 79% for T3, and 44% for T4. Out of 61 local progressive tumors 27 (44%) were salvaged with abdominoperineal resection (APR). The rate of local tumor relapse (LTR) was 15% for T1, 9% for T2, 16% for T3, and 12% for T4. Out of 37 LTR, 20 (54%) were salvaged with APR and one with interstitial 192Ir Bcy. Local tumor control (LTC) rate with or without salvage local treatment was: 92% for T1, 91.5% for T2, 82% for T3, and 50% for T4. Eleven pts had pretreatment permanent colostomy and one APR was made for clinical residual tumor but no cancer was found on histologic examination. Colostomy and APR for trophic deficiences were performed on 11 and 6 cases, respectively. The rate of LTC with sphincter conservation was 81% for T1, 68.5% for T2, 58% for T3, and 23.5% for T4. However, the rate of good anal function scoring with LTC was: 69% for T1, 63% for T2, 53% for T3, and 23.5% for T4. None of the factors studied (characteristics of tumor and technique of RT) had a significant influence on the good anal function scoring for pts with LTC. In 14 inguinal local nodal relapses, 5 were rescued after salvage inguinal nodal resection and/or RT. None of 5 local progressive inguinal nodes were rescued after salvage treatment. Metastases were observed in 31 pts. The 10-year disease-free survival rate was 76% for T1, 88.5% for T2, 65.5% for T3, and 41.5% for T4. For a subgroup of 15 pts with length tumor ⬍ 2 cm-N0, the local complete response after the end of RT was 100% the LTC with a good anal function scoring was 96%, and the 10-year disease-free survival rate was 80.5%. Conclusions: We confirm excellent results with RT in T1 and T2 lesions. However, chemoradiotherapy should be prefered to improve survival free of colostomy with a good anal sphincter function for tumors more than or equal to 2 cm in length and locally advanced tumors.

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The Effect on Toxicity of Induction Hormonal Therapy in Prostate Cancer Patients Receiving Dose Escalated 3D Conformal Radiation Therapy on RTOG 94-06

R.K. Valicenti1, K. Winter2, J.D. Cox3, H. Sandler4, W. Bosch5, J. Michalski6 1 Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, 4University of Michigan, Ann Arbor, MI, 5QA Center, Washington University, St. Louis, MO, 6Washington University, St. Louis, MO Purpose/Objective: This study determines the effect on toxicity by the addition of induction hormonal therapy (HT) to 3D conformal radiation therapy (3D CRT) in RTOG 94-06. Materials/Methods: Between 8/94 and 2/00, 583 eligible prostate cancer patients enrolled on the first three dose levels of RTOG 94-06, a phase I/II dose escalation 3D CRT trial. Two hundred and seven men initiated HT between 2 to 3 months prior to 3D CRT, and completed all HT no longer than 3 months after radiotherapy. 36 continued HT more than 3 months after completing radiotherapy and were excluded. The 547 patients evaluable for this analysis of toxicity were treated at dose level I (68.4 Gy), level II (73.8 Gy), or level III (79.2 Gy). All dose prescriptions were to the minimum isodose surface encompassing the planning target volume (PTV) (dose levels I and II) or the clinical target volume (CTV) (dose level III). Men were stratified into 3 risk groups according to their relative risk of seminal vesicles (SV) invasion:⬍15% (Group I) vs. ⬎15% (Group II) or to T stage (T1, 2 vs. T3 tumors (Group III)). In Group II patients only, there was a CTV reduction to treat only the prostate after delivery of 55.8 Gy to a PTV including the SV. All HT consisted of an LHRH agonist with or without a non-steroidal anti-androgen. The rates of acute and late effects ⱖ grade 2 were compared between groups of patients receiving induction HT or no HT in addition to 3D CRT. Results: The distribution of patients according to group, dose level, and induction HT is summarized in Table 1. The majority of men (50%) were treated on dose level II to 73.8 Gy. On univariate analysis, induction HT significantly increased the likelihood of acute GU effects ⱖ grade 2 (22% to 32%, p⫽0.009). Hormonal therapy did not have a significant effect on any other acute or late toxicity. On multivariate analysis, the variable: percent of the bladder receiving ⱖ the reference dose (ⱕ 30% vs. ⬎30%) was an independent predictor of acute GU effects (p⫽0.0009, RR⫽2.07, CI:1.88-2.28). Although induction HT was

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