Neoadjuvant Accelerated Concomitant Boost Radiotherapy and Multidrug Chemotherapy in Locally Advanced Rectal Cancer: A Dose-Escalation Study.
ABSTRACT OBJECTIVES: To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients. METHODS: Patients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria. RESULTS: Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level. CONCLUSIONS: An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.
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ABSTRACT: To present the impact of a novel minimization device, the up down table (UDT), on the volume of small bowel included within a 4-field pelvic irradiation plan. A polystyrene bowel displacement standard mold was created and added to a customized vacuum cushion (Vac Lok) formed around the abdomen and legs of each patient in the prone position. Two hundred seventy-seven consecutive patients with pelvic malignancies treated with the UDT device were compared with 1 historic series (68 cases) treated at our division. Small bowel contrast dyes at the time of simulation were used in all patients. The average volume of small bowel within the planning target volume (high-dose volume, calculated with Gallagher method) was 100 cm(3) (median 49 +/- 114) in the series treated with standard box technique and 23 cm(3) (median 0 +/- 64) in the series treated with the UDT (p < 0.001). The average volume of small bowel included in any isodose (any-dose volume) was 505 cm(3) (median 447 +/- 338) and 158 cm(3) (median 69 +/- 207), respectively (p < 0.001). The incidence of G1, G2, and G3 acute enteric toxicity (Radiation Therapy Oncology Group criteria) in the UDT series was 16%, 15%, and 1.5%; in the standard box technique, it was 28%, 25%, and 3%, respectively (p < 0.05). The incidence of acute enteric toxicity directly correlated with the irradiated small bowel volume. In the UDT series, the 5-year actuarial incidence of G3 chronic enteric toxicity was 1.8%. The setup procedures, analyzed in 18 cases, revealed no systematic errors and a standard deviation equal to +/-5 mm for random errors. The UDT technique is comfortable, inexpensive, highly reproducible, and permits an almost full bowel displacement from standard radiotherapy fields.International Journal of Radiation OncologyBiologyPhysics 10/2001; 51(2):465-73. · 4.52 Impact Factor
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ABSTRACT: Anticancer cytotoxic agents go through a process by which their antitumor activity-on the basis of the amount of tumor shrinkage they could generate-has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical research combined forces to tackle the review of these criteria on the basis of the experience and knowledge acquired since then. After several years of intensive discussions, a new set of guidelines is ready that will supersede the former criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines. This special article also provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified, briefly within the guidelines and in more detail in Appendix I. All other aspects of response evaluation have been discussed, reviewed, and amended whenever appropriate.JNCI Journal of the National Cancer Institute 03/2000; 92(3):205-16. · 14.34 Impact Factor
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ABSTRACT: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003). The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.International Journal of Radiation OncologyBiologyPhysics 07/2000; 47(3):713-8. · 4.52 Impact Factor