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PURPOSE To evaluate the patterns of tumor shape and to compare tumor volume derived from simple diameter-based ellipsoid measurement with that derived from tracing the entire tumor contour using region of interest (ROI)-based 3D volumetry with respect to the prediction outcome in cervical cancer patients treated with concurrent chemotherapy and radiotherapy. MATERIALS AND METHODS Magnetic resonance imaging was performed in 98 patients with cervical cancer (stage IB-IIIB). The tumor shape was classified into two categories: ellipsoid and non-ellipsoid shape. ROI-based volumetry was derived from each magnetic resonance slice on the work station. For the diameter-based surrogate "ellipsoid volume," the three orthogonal diameters were measured to calculate volume as an ellipsoid. RESULTS The more than half of tumor (55.1%) had a non-ellipsoid configuration. The predictions for outcome were consistent between two volume groups, with overall survival of 93.6% and 87.7% for small tumor (

17041 Background: The prognosis of patients with RH&NSCC remains dismal, with a median survival of 4 months without treatment and 6 months with palliative chemotherapy. Surgery remains the best tre...

7569 Background: Standard treatment of stage III NSCLC remains concurrent chemotherapy and TRT. However, not all chemotherapy drugs can be combined with TRT at full systemic dosages. We are conduct...

7520 Background: The combination of chemotherapy (CT) and radiotherapy (RT) is standard of care in the treatment of inoperable stage III NSCLC. The aim of this trial was to assess whether the addit...

15593 Background: IMRT allows delivery of a radiation (RT) dose distribution that conforms to the shape of complex or multiple targets and avoidance structures as in anal cancer. The improvement in...

7545 Background: Randomized clinical trials have failed to show a survival benefit for small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus chemotherapy in unselected patients with metastatic NSCLC. In contrast, pilot trials of EGFR targeted antibodies plus chemotherapy have suggested enhanced anti-tumor activity. This randomized phase II selection trial was designed to select a cetuximab-chemotherapy regimen for future evaluation in a phase III setting. Methods: Untreated patients (pts) with advanced stage NSCLC were randomized to receive paclitaxel (P) 225 mg/m2 and carboplatin (Cb) AUC=6 every 3 weeks plus concurrent cetuximab (C) 400 mg/m2 loading dose followed by 250 mg/m2, weekly for 4 cycles followed by maintenance C or sequential PCb for 4 cycles followed by C. Treatment was continued until disease progression. Eligible patients were required to have stage IIIB (pleural effusion) or IV (without brain metastases) disease, a performance status of 0–1 and adequate organ function. The primary endpoint was overall survival. The regimen with superior median survival would be considered for further evaluation provided it met a 10-month minimum. Given a true hazard ratio of 1.3, the probability of correctly choosing the superior arm would be > 90%. Results: From July 2004 to June 2005, 242 eligible pts were enrolled onto the study, Final results are described below: Conclusions: Both regimens met efficacy criterion for continued evaluation though the concurrent regimen of PCb + C, had numerically higher survival, and was chosen for further study. Some toxicities were significantly increased with concurrent therapy. A phase II trial of PCb + Cetuximab + Bevacizumab is ongoing (SWOG 0536) in anticipation of a phase III trial. Molecular correlative studies of the EGFR signaling pathway including EGFR IHC, FISH and mutation analysis are underway. No significant financial relationships to disclose. [Table: see text]

2021 Background: Standard therapy for glioblastoma, which includes surgery followed by radiation and concurrent chemotherapy, creates a low tumor burden environment that could be ideal for immunotherapeutic approaches. We conducted a Phase I study to assess the safety and immunologic responses of tumor lysate-pulsed dendritic cell (DC) therapy plus topical imiquimod, in combination with standard radio-chemotherapy. Methods: Thirteen patients with newly diagnosed glioblastoma were immunized using autologous tumor lysate-pulsed DC. Each patient initially received 3 immunizations at 2-week intervals, following completion of a 6-week course of radio- chemotherapy. Four patients received 1 million DC, 4 received 5 million, and 5 received 10 million DC per immunization. Patients without tumor progression subsequently received booster vaccinations combined with topical administration of the TLR-7 agonist imiquimod. Immunologic responses to tumor antigens were monitored by HLA-restricted tetramer staining, CTL assays, and quantitation of T-regulatory cells. Clinical tumor growth was monitored by brain MRI scans every 2 months, and the primary clinical endpoint was 2-year survival. Results: All immunizations were well tolerated, with only mild side effects attributable to the DC vaccination and imiquimod adjuvant. Increased levels of CD8+ T cells reactive against tumor antigens, (e.g., gp100, TRP-2, her-2, survivin, and CMV antigens), were detected in 5 patients. Median PFS and OS have not been reached in this trial. To date, 6 of the 13 patients have progressed, and 4 of those have died. The median PFS to date is 18.1 mos. and median OS is 33.8 mos. This compares favorably with controls from the published literature, with a median PFS of 6.9 mos and OS of 14.6 mos. Conclusions: This study demonstrates the safety and clinical/immunologic effects of an autologous tumor lysate-pulsed DC vaccine for patients with newly diagnosed glioblastoma. The adjunctive use of the TLR-7 agonist imiquimod with DC vaccination appears to be non-toxic, and deserves further study. We demonstrate that this active immunotherapy strategy can generate antigen-specific immunologic responses in brain tumor patients following standard radio-chemotherapy. No significant financial relationships to disclose.

7717 Background: Accelerated fractionation proved beneficial in INT0096, but the total dose was low and local recurrence was high with higher acute grade (Gr.) 3+ esophagitis. RTOG 0239 was a phase II trial to improve local control and survival with LSCLC with acceptable acute Gr. 3+ esophagitis using accelerated high dose TRT and concurrent cisplatin/etoposide. This is the first report of acute Gr.3+ esophagitis and Gr.5 toxicities. Methods: Patients (pts) with LSCLC without pleural effusion, contralateral hilar or contralateral supraclavicular nodes and PS 0–1 were enrolled. TRT was given to large fields to 28.8 Gy at 1.8 Gy per fraction, 5 days per week for 16 fractions followed by BID with large field in AM, boost in PM, then off-cord boost BID for last 5 days, all at 1.8 Gy per fx for a total dose of 61.2 Gy in 34 fx in 5 weeks. Concurrent chemotherapy was started with TRT with cisplatin, 60 mg/m2 i.v. day 1; etoposide, 120 mg/m2 i.v. day 1; etoposide, 240 mg/m2 p.o. per day or 120 mg/m2 i.v. per day on days 2 or 3. Cycles were repeated q.3 wks during and for 2 cycles after TRT. Pts who have achieved complete response one month after completion of 4 cycles of chemotherapy were asked to participate in a prophylactic cranial irradiation (PCI) study. Common toxicity criteria (CTC) 2.0 was used for acute toxicity. Results: From 10/2003 to 5/2006, 72 pts were accrued. Median age was 63 yrs with 52% females. Survival data is still maturing. Acute toxicity information is available for 68 pts. Eleven pts (16%) experienced acute Gr. 3 and 1 pt (1%) had acute Gr. 4 esophagitis. 47 pts (69%) had grade 4 blood/bone marrow toxicities. There were 2 (3%) Gr. 5 toxicities reported [1 infection with neutropenia; 1 pulmonary (pneumonia)]. Conclusions: This accelerated high dose TRT with concurrent chemotherapy for LSCLC resulted in 17% acute Gr.3+ esophagitis compared to 27% with BID TRT with 45Gy in 3 weeks by INT0096. There were 3% grade 5 toxicities. This preliminary report suggests that RTOG-0239 has tolerable toxicity. The acute Gr3+ esophageal toxicity correlated with V20 and V40 will be presented. Pts continue to be followed for the primary endpoint of 2-year survival. No significant financial relationships to disclose.

7145 Background: Combined modality treatment is the standard of care for patients (pts.) with unresectable stage III NSCLC. Dose escalation of radiotherapy and the use of concurrent chemotherapy are two strategies attempting to improve survival and locoregional control. The intensification of therapy increases the risk of both early and late treatment related toxicities. Methods: From 5/1996 to 8/2004, 112 stage III NSCLC pts. were entered into 4 Phase I/II trials to assess the safety and feasibility of high-dose (74–90 Gy) thoracic conformal radiotherapy (TCRT) in QD or BID fractions. All pts. were treated with platinum-based induction chemotherapy; 3 of the trials also used concurrent chemotherapy. Results: The median follow up of survivors (29/112) on these trials was 4.9 years. The overall response rate after combined modality therapy was 47% (53/112) (CR 4%, 5/112; PR 43%, 48/112). 27% (30/112) had stable disease. The median survival (with 95% CI) was 24 months (18–31 months). 1-, 3-, and 5-year overall survival was 69% (60–77%), 36% (27–45%), and 24% (16–33%) respectively. Late complications of therapy (defined as >90 days post radiotherapy reported to date) are displayed in the table. Two pts. developed a second primary (1 lung, 1 liver carcinoid). In total, 22% (25/112) had late complications. These patients appear to have a significantly better overall survival (p = .007). 12% (13/112) had a brain-only recurrence, although this did not seem to significantly impact overall survival (p = .82). Conclusions: 1) High-dose TCRT is feasible and results in promising survival outcomes. 2) Late complications occur in a minority of patients suggesting the potential benefit of more aggressive TCRT is not outweighed by its risk. 3) Interestingly, brain-only recurrences did not significantly impact survival in these trials. [Table: see text] [Table: see text]

5542 Background: The superiority of concurrent high dose cisplatin and radiation (RT) compared to RT alone for pts with locally advanced squamous cell cancer of the head and neck (SCCHN) has been demonstrated in large prospective phase III clinical trials. However, little is known regarding general prescribing patterns for chemotherapy (CT) utilization in combined modality treatment (CMT) for SCCHN. We conducted the present study to gain insight as to whether results from pivotal phase III trials affect utilization of concurrent CT in academic and community centers. Methods: We analyzed individual data from 326 SCCHN pts treated with concurrent CT and RT between 03/2003 and 12/2004 from 53 centers (43 community-based, 7 academic, and 3 VA or military) using electronically captured data from IntelliDose, a chemotherapy order software program. Results: Of 326 total pts, 123 pts (38%) received single agent cisplatin. From this group, 71 (58%) received low dose cisplatin (2, mean initial dose 67 mg), while 52 patients (42%) received high dose cisplatin (≥ 74 mg/m2, mean initial dose 189 mg). 72 pts (22%) received carboplatin/paclitaxel, 60 pts (18%) received cisplatin /5FU, 18 pts (5.5%) received single agent carboplatin, while 6 pts (1.8%) received cetuximab either alone or in combination with cisplatin. Other infrequently used regimens (each < 5%) cumulatively accounted for 14% of pts treated. Comparison of chemotherapy utilization between academic and community-based practice centers showed no statistical difference with respect to use of high dose cisplatin versus low dose cisplatin, or single agent cisplatin versus non-cisplatin regimens. Conclusions: Despite evidence from phase III studies that concurrent high dose cisplatin is the standard of care for CMT of locally advanced SCCHN, utilization of other regimens, such as weekly low dose cisplatin, are commonly utilized. [Table: see text]

5559 Background: Despite aggressive therapy, over 70% of locally advanced squamous cell carcinomas of the head and neck (SCCHN) fail primary treatment. Salvage therapy with surgery, chemotherapy or brachytherapy alone or in combination has a 30–40% response rate, but few long-term survivors. Re-irradiation with concurrent chemotherapy for SCCHN has recently become a well established approach after two consecutive cooperative group studies were reported. Intensity Modulated Radiation Therapy (IMRT) is a new and safer way to deliver radiation therapy. This retrospective review evaluated the potential benefit and toxicity using every other week IMRT with concurrent chemotherapy. Design: Thirty-seven patients with locally recurrent SCCHN were evaluated. All patients received re-irradiation with IRMT every other week with concurrent weekly carboplatin (median AUC= 2) or cisplatin (60–100 mg/m2) ± 5-FU (800–1000 mg/m2) or paclitaxel 175mg/m2 every three weeks. Patients received 6000 cGy at 200 cGy per fraction. Results: The median follow-up time was 12 months. The overall response rate was 75.7% with a complete response (CR) and partial response (PR) of 56.8% and 18.9%, respectively. Among complete responders, 33% recurred locally in a median time of 5 months. The Kaplan-Meier estimate of disease-free survival, progression-free survival, and overall survival at 48 months is 58%, 45%, and 28%, respectively. At the time of last follow-up, 51.4% of patients were still alive and 27.8% of patients had no evidence of disease. Grade 3 or 4 acute toxicities occurred in 20% of patients of which 13.3% were hematologic requiring either growth factors or delay in chemotherapy. No deaths occurred during the course of treatment. Long-term complications consisted of one patient with an esophageal stricture requiring repeated dilations, 2 patients with chronic dysphagia, and 2 patients developing a pharyngeal-cutaneous fistula, one of which died from a carotid blowout occurring 6 months after treatment. Conclusions: IMRT delivered every other week with concurrent platinum based chemotherapy produces good responses with only moderate toxicity in patients previously treated with radiation therapy for recurrent head and neck cancer. No significant financial relationships to disclose.

7015 Background: Randomized clinical trials have failed to show a survival benefit for small molecule EGFR tyrosine kinase inhibitors plus chemotherapy in patients with advanced NSCLC. In contrast, pilot trials of EGFR targeted antibodies plus chemotherapy have suggested enhanced anti-tumor activity. This large randomized phase II trial was designed to select a cetuximab -chemotherapy regimen for future evaluation in a phase III setting. Methods: Untreated patients (pts) with stage IIIB (by pleural effusion) or IV (without brain metastases) NSCLC, with a performance status of 0–1 and adequate organ function were randomized to received paclitaxel (P) 225 mg/m2 and carboplatin (Cb) AUC=6 every 3 weeks plus cetuximab (C) 400 mg/m2 loading dose followed by 250 mg/m2, weekly for 4 cycles followed by maintenance C or the same doses of PCb for 4 cycles followed by C. C was continued until disease progression or 1 year of therapy. The primary endpoint was overall survival; the statistical design required a median survival of ≥ 10 months for a regimen to be selected for subsequent phase III trial evaluation. The probability of correctly choosing the superior arm is 91% when the true hazard ratio is 1.3. Results: From July 2004 to June 2005, 225 eligible pts were enrolled into the study. Preliminary results are described below: Conclusions: At the time of this analysis, efficacy and toxicity were similar in the two treatment arms; both regimens were well tolerated. Assuming these results are sustained, the concurrent regimen of PCb + cetuximab has met the criteria for continued evaluation. A phase II trial of PCb + cetuximab + bevacizumab (B) is in development in anticipation of a phase III trial testing PCbB ± cetuximab. Molecular correlative studies of the EGFR signaling pathway are ongoing. [Table: see text] [Table: see text]

5544 Purpose: Retrospective review of an institution’s IMRT experience in treating advanced laryngeal/hypopharyngeal carcinoma with concurrent chemotherapy. Methods: Between 1/02–6/05, 31 patients with advanced laryngeal/hypopharyngeal carcinoma (74% T3/T4 disease;71% stage IV) underwent combined modality treatment. There were 20 laryngeal and 11 hypopharyngeal carcinomas. All patients received definitive IMRT with a median RT dose of 70 Gy. Concurrent chemotherapy was also given to all patients [cis-platinum (100mg/m2/cycle) or carboplatin/5-fluorouracil (J Clin Oncol 2004;22:69) every 3 weeks for 2–3 planned cycles; 3 patients received a weekly paclitaxel/carboplatin program]. Prophylactic feeding tubes (PEG) were placed in all patients. Acute toxicity and late xerostomia were scored using the RTOG radiation morbidity scale. The 2-year estimates for local progression-free rate (LPF), regional progression-free rate (RPF), distant metastases-free rate (DMF), and overall survival (OS) were calculated using the Kaplan-Meier method. Results: With a median follow-up of 17 months (range: 7–48), 2-year estimates of LPF, RPF, DMF, and OS rates were 76%, 94%, 96%, 87%, respectively. All patients with local failure of laryngeal carcinoma had persistent disease at the end of treatment. Grade ≥2 mucositis was experienced by 68% of the patients during treatment. Xerostomia continued to decrease over time from the end of RT and only 4 still complained of Grade 2 xerostomia. A greater proportion of patients with hypopharynx than larynx cancer were still PEG-dependent (55% versus 25%) after combined modality treatment at the time of this analysis. One patient developed laryngeal necrosis. Conclusions: These preliminary results show that IMRT, in combination with chemotherapy, achieved encouraging local control rates in patients with advanced laryngeal/hypopharyngeal carcinoma. Xerostomia improved over time. Pharyngoesophageal stricture with PEG dependency remains a problem especially in patients with hypopharyngeal carcinoma. Strategies using the ability of IMRT to limit the dose delivered to the esophagus and inferior constrictor musculature may be useful to further minimize this late complication. No significant financial relationships to disclose.

5543 Background: Concurrent chemotherapy/radiation therapy (RT) improves treatment outcome in pts with locally advanced unresectable squamous cancers of the head and neck. We previously reported a 51% 3-year disease-free survival with induction paclitaxel/carboplatin/5-FU followed by concurrent paclitaxel/carboplatin/RT. In this phase II trial, we added gefitinib, an EGFR inhibitor, to a similar chemoradiation regimen. Methods: All pts had squamous carcinoma of the head and neck, with at least one of the following: N1-N3 disease, T3 or T4 primary lesion, nasopharynx primary (except T1N0M0). Additional eligibility: no previous therapy, ECOG PS 0 or 1, adequate bone marrow, kidney, liver function; informed consent. All pts received initial docetaxel 60mg/m2 D1, 22; carboplatin AUC 5.0 D1, 22; 5-FU 200mg/m2, 24-hour CI, D1–43; gefitinib 250mg PO qd, D1–43. Beginning week 8, pts received RT, 1.8Gy single daily dose to total 68.4 Gy, and concurrent docetaxel 20mg/m2 weekly × 6 doses + gefitinib 250mg PO daily. At completion of therapy, pts were reevaluated with CT scans and endoscopy. Results: 45 pts entered this trial between 8/04 and 8/05. Pertinent clinical characteristics: clinical T3/T4, 17; N2/N3, 23. 42 pts (93%) completed induction chemotherapy. 34 pts (76%) have completed combined modality therapy and have been restaged. Response to treatment: 11 CR (32%); 18 PR (53%); 5 stable/progression (15%). After median follow-up 7 months, 9 patients (20%) have developed progressive cancer. Actuarial PFS and OS at 1 year are 68% and 86%, respectively. Grade 3/4 myelosuppression was common, and grade 3/4 mucositis occurred in all pts during combined modality therapy. One pt had a treatment-related death during combined modality therapy. The addition of gefitinib did not substantially increase toxicity. Conclusions: This combined modality regimen was feasible and produced high response rates in pts with locally advanced head and neck cancer. Toxicity was consistent with other effective combined modality regimens for these pts. Further follow-up is needed to better assess the benefit of this approach. [Table: see text]

3588 Background:At McGill University, conformal therapy has been introduced in the treatment of patients with anal cancer to alleviate treatment related acute toxicities in one of the two radiation...

3626 Background: In 1992 preop RT was considered in France as the standard treatment for T3,4 rectal cancer. The aim of this trial was to investigate a potential survival (S) benefit by using concurrent chemotherapy (CT). Methods: Eligibility criteria included: rectal adenocarcinoma accessible to digital rectal examination, resectable T3,T4NxM0, < 80 years, written informed consent. According to stratification criteria (sex/ T3-T4/ tumoral localisation), 762 patients (pts) were randomized between RT alone and CT/RT to demonstrate a 10% benefit in 5 year S (from 52% to 62%). RT involved 45 Gy in 25 fractions/5 weeks (wks) with Xray ≥ 8 MV. Concurrent CT consisted of bolus 5FU 350 mg/m2 and FA 20 mg/m2 IV days 1–5 (FUFA) on wks 1 and 5. Surgery was performed 3 -10 wks later. Then all pts had to receive 4 adjuvant FUFA cycles. Results: Preliminary analysis was performed on 685 eligible pts included between 4/1993 -11/2003. Pts' clinical characteristics were well-balanced between arms: median age 61 years, m/...

4074 Background: This is a preliminary analysis of a phase II trial addressing the optimal integration of hyperfractionated radiation and concurrent chemotherapy in the pre-operative setting for pa...

7014 Background: Surgery after CT/RT remains controversial for patients (pts) with stage IIIA(pN2) NSCLC. Initial analyses of INT 0139 showed significantly better progression-free survival (PFS), but not overall survival (OS), in the trimodality arm. (PASCO 2003) With longer follow-up (≥2.5 yrs per pt), new analyses of primary endpoints PFS and OS were conducted. Methods: Pts with PS 0–1 and T1–3, pN2, M0 NSCLC were randomized if resection was technically feasible. All received cisplatin 50 mg/m2 d1, 8, 29, 36 and etoposide 50 mg/m2 d1–5, d29–33 (PE) and RT to 45 Gy starting day 1. Arm 1 had resection if no progression (PD), then PE X2; Arm 2 completed RT to 61 Gy with PE X2. Intent to treat analyses used Kaplan-Meier estimates, log-rank tests and Cox multivariate models; exploratory analyses used logistic regression. All CI are 95% and p-values, 2-sided. Results: 396 eligible pts were enrolled (Arm 1, 202; Arm 2, 194; well-balanced on all factors). Treatment-related deaths: Arm 1, 16 (7.9%), of which 10 ...

5113 Background: Compare, retrospectively, the results in terms of toxicity, clinical overall response, disease free survival (DFS) and survival (S) at 2 years of two different CH schemes: A) Gemci...

5545 Background: To examine the feasibility and efficacy of weekly docetaxel with concurrent radiation as postoperative treatment in a multimodality approach to oral and oropharyngeal cancer. Metho...

7158 Background: HFXRT has not been commonly used in community practice despite better 5-yr survival compared to QDRT with concurrent cisplatin and etoposide by randomized study. Methods: CT-staged...

3562 Background: Concurrent chemotherapy and radiation is standard treatment of patients with locally advanced rectal cancer. Most patients have only limited effect and there is an obvious need for...

4760 Background: To report safety and efficacy of endobronchial brachytherapy (EBT) combined with external beam radiation (ER) with or without concurrent chemotherapy in patients with bronchial obs...

5525 Background: Concurrent chemoradiation (RCT) might be first treatment of choice in advanced unresectable HNC. Between 1995 and 1999 a two arm multicentric randomized study with hyperfractionate...

7063 Background: The standard radiation dose for NSCLC was established by RTOG 7301 as 60 Gy. Local failure rates with this dose remain unacceptably high. Current cooperative group trials continue to use doses of 60–63 Gy in the setting of concurrent chemotherapy. The primary endpoint of the Phase I portion was to establish the maximum tolerated dose (MTD) of radiation therapy, in the setting of concurrent chemotherapy, using 3DCRT for NSCLC. Methods: Eligibility included patients with histologically proven, unresectable Stages I-III NSCLC and a Zubrod perfomance status of 0–1. Weight loss eligibility was ≤10%. Concurrent chemotherapy consisted of paclitaxel 50 mg/m2 and carboplatin AUC=2 given weekly. Radiation dose was to be sequentially intensified by increasing the daily fraction size starting at 75.25 Gy/35 fractions. Interim analysis was planned after the initial 7 patients were enrolled with application of the stopping rule if DLTs occurred in 2 or more patients. Radiation therapy volumes consisted...