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Vincent Gregoire - One of the best experts on this subject based on the ideXlab platform.
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a Dose escalation study with intensity modulated radiation therapy imrt in t2n0 t2n1 t3n0 squamous cell carcinomas scc of the oropharynx larynx and hypopharynx using a simultaneous integrated boost sib approach
Radiotherapy and Oncology, 2013Co-Authors: Mathieu Leclerc, P Maingon, Marc Hamoir, C Dalban, G Calais, Sandra Nuyts, Antoine Serre, Vincent GregoireAbstract:Background The simultaneous integrated boost (SIB) technique with Dose per fraction slightly higher than 2 Gy offers the advantages of shortening the treatment time and increasing the biologically equivalent Dose to the tumor. This study was designed to evaluate the feasibility of a Dose-escalating radiotherapy treatment by using a SIB-IMRT approach in patients with early and moderately advanced head and neck cancers. Materials and methods Fifty-seven consecutive patients with pharyngo-laryngeal T2N0 or T2N1, or laryngeal T3N0 SCC were included. The therapeutic PTVs were treated according to three consecutive Dose Levels i.e., 69 Gy in 30 fractions of 2.3 Gy (Dose Level I), 72 Gy in 30 fractions of 2.4 Gy (Dose Level II) or 75 Gy in 30 fractions of 2.5 Gy (Dose Level III). The prophylactic PTVs received a Dose of 55.5 Gy delivered in 30 fractions of 1.85 Gy. The primary endpoint of the study was acute toxicity assessed during treatment and during the first 3 months following the completion of radiotherapy. The secondary endpoints included loco-regional control, disease-free survival, overall survival and late toxicity at 2 years of follow-up. The study design allowed patients to be enrolled in the second Dose Level group if no more than 10% of grade 4 acute toxicity was observed on the first Dose Level group within 3 months after the completion of IMRT, and so on for the third Level group. Results Forty-four men and 13 women were included in the trial. The majority of them presented with oropharyngeal cancer (53%) and laryngeal cancer (33%). Only 3 patients developed grade 4 acute mucositis during treatment, one in each Dose Level. Thirty-two patients (56%) experienced grade 3 toxicity, mostly dermatitis and mucositis, without any significant difference between the groups. Late grade 1 and 2 xerostomia was seen in 53% and 33% of patients, respectively. Transient grade 4 late toxicity was observed in 16% of all patients and was equally distributed among the groups. The 2-year loco-regional control was 82% for all 3 groups (79% Dose Level I, 88% Dose Level II, 79% Dose Level III). The 2-year overall survival was 89% for Dose Level I and II, and 95% for Dose Level III. Conclusions This Dose escalation SIB-IMRT protocol was safe and effective as the sole treatment of early and moderately advanced SCC of head and neck. No toxicity difference was observed between the groups.
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positron emission tomography guided focal Dose escalation using intensity modulated radiotherapy for head and neck cancer
International Journal of Radiation Oncology Biology Physics, 2007Co-Authors: Indira Madani, Vincent Gregoire, Werner De Gersem, Wim Duthoy, Cristina Derie, Tom Boterberg, Mickey Saerens, Filip Jacobs, Max Lonneux, Luc VakaetAbstract:PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided Dose escalation, and to determine the maximum tolerated Dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the Dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two Dose Levels were planned: 25 Gy (Level I) and 30 Gy (Level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at Dose Level I, and 18 at Dose Level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of Dose-limiting toxicity occurred at Dose Level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at Dose Level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at Dose Levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at Dose Levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided Dose escalation appears to be well-tolerated. The maximum tolerated Dose was not reached at the investigated Dose Levels.
Evan R Reiter - One of the best experts on this subject based on the ideXlab platform.
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simultaneous integrated boost intensity modulated radiotherapy for locally advanced head and neck squamous cell carcinomas ii clinical results
International Journal of Radiation Oncology Biology Physics, 2004Co-Authors: A Lauve, Monica M Morris, Rupert Schmidtullrich, Radhe Mohan, Olubumni Abayomi, David A Buck, Diane Holdford, Kathryn S Dawson, Laurence J Dinardo, Evan R ReiterAbstract:Abstract Purpose To perform a Phase I radiation Dose-escalation trial to determine the maximal tolerable Dose (MTD) deliverable to the gross tumor volume (GTV) using an accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole therapy in the treatment of locally advanced head-and-neck squamous cell carcinoma. The primary objective was the definition of the MTD using established criteria of quantifying acute Dose-limiting toxicity (DLT). Secondary objectives included analysis of failure patterns, tumor control rates, and toxicity. Methods and materials Between July 1999 and June 2002, eligible patients with bulky Stage II to Stage IVB head-and-neck squamous cell carcinoma, excluding laryngeal primaries, were enrolled. Intensity-modulated radiotherapy was delivered with 6-MV photons using a “sliding-window” technique. Enrollment of 6 patients for each Dose Level was planned; if DLTs were seen in >2 of 6 patients, the previous Dose was to be expanded by an additional 6 patients to confirm that Dose Level as the MTD. All schedules administered a total of 30 fractions, but with escalating Doses per fraction (2.27, 2.36, and 2.46 Gy) to achieve a total Dose to the GTV of 68.1, 70.8, and 73.8 Gy, respectively. The remaining target tissues were constrained to receive the same Dose in all patients regardless of the GTV Dose Level. The clinical target volume, defined as tissue within 1 cm around the GTV (at high risk of subclinical disease), received 60 Gy in 30 fractions of 2.0 Gy. The electively irradiated target volume, defined as the clinically uninvolved lymph node-bearing tissues, received 54 Gy in 30 fractions of 1.8 Gy. The parotid glands were spared to the degree possible without compromising target coverage. Acute toxicity was scored weekly using National Cancer Institute Common Toxicity Criteria. DLT was defined as any Grade 4 acute toxicity or any acute toxicity requiring either a Dose reduction or a treatment break of >5 treatment days. Results Of 18 men and 2 women (average age, 57 years; range, 37–80 years), 17 presented with oropharyngeal primary tumors, and 1 each with squamous cell carcinoma of the oral cavity, nasopharynx, and hypopharynx. None of the 6 patients at Dose Level 1, and 2 of the 6 patients initially enrolled at Dose Level 2, developed DLT. Both patients treated at Dose Level 3 required a 3-day treatment break and Dose reduction after rapid development of Grade 3 toxicity (by Day 15). Six additional confirmatory patients subsequently enrolled at Dose Level 2 completed treatment without DLT. At least 50% of the total parotid gland volume received Conclusion Dose Level 2, 70.8 Gy in 30 fractions of 2.36 Gy, was defined as the MTD deliverable to the GTV using this accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole treatment for locally advanced head-and-neck squamous cell carcinoma. Adequate parotid sparing was achievable in most cases. Early toxicity, tumor control, and survival rates compared favorably with the outcomes after other accelerated regimens.
Priyanka Bhateja - One of the best experts on this subject based on the ideXlab platform.
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phase i study of the combination of quinacrine and erlotinib in patients with locally advanced or metastatic non small cell lung cancer
Investigational New Drugs, 2018Co-Authors: Priyanka Bhateja, Afshin Dowlati, Neelesh SharmaAbstract:Introduction Preclinical data suggest quinacrine acts as an inhibitor of FACT (facilitates chromatin transcription) complex, which may play a role in TKI (tyrosine kinase inhibitor) resistance. The aim of this Phase I study was to study the safety and assess the maximum tolerated Dose of quinacrine in combination with erlotinib in non small cell lung cancer (NSCLC). Methods This was a phase I study with standard 3 + 3 Dose escalation design with the primary aim of determining the maximum tolerated Dose. Two of 3 patients enrolled at Dose Level 1 experienced Dose limiting toxicity (DLT). The next 6 patients were enrolled at Dose Level − 1 and none of these 6 patients experienced DLT. The Dose of 50 mg of quinacrine every other day with 150 mg of erlotinib was established as the maximum tolerated and the recommended phase II Dose. One of 3 patients treated at Dose Level 1 had stable disease. One of 6 patients treated at Dose Level − 1 had partial response for 6 months, the rest had progressive disease at the time of first assessment. Conclusion Combination of quinacrine and erlotinib was well tolerated but showed limited efficacy in advanced NSCLC.
Indira Madani - One of the best experts on this subject based on the ideXlab platform.
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adaptive Dose painting by numbers for head and neck cancer
International Journal of Radiation Oncology Biology Physics, 2011Co-Authors: Frederic Duprez, Wilfried De Neve, Werner De Gersem, Marc Coghe, Indira MadaniAbstract:Purpose To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using Dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials Each patient's treatment used three separate treatment plans: fractions 1–10 used a DPBN ([ 18 -F]fluoro-2-deoxy-d-glucose positron emission tomography [ 18 F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment 18 F-FDG-PET/computed tomography (CT) scan; fractions 11–20 used a DPBN plan based on a 18 F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21–32 used a conventional (uniform Dose) IMRT plan. In a Phase I trial, two Dose prescription Levels were tested: a median Dose of 80.9 Gy to the high-Dose clinical target volume (CTV high_Dose ) (Dose Level I) and a median Dose of 85.9 Gy to the gross tumor volume (GTV) (Dose Level II). Between February 2007 and August 2009, 7 patients at Dose Level I and 14 patients at Dose Level II were enrolled. Results All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation ( i.e., plans based on the second 18 F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV high_Dose (18%, p = 0.01), high-Dose planning target volume (14%, p = 0.02), and parotids (9–12%, p high_Dose and target adaptation, further Dose escalation at Dose Level II resulted in less severe toxicity than that observed at Dose Level I. Conclusion To our knowledge, this represents the first clinical study that combines adaptive treatments with Dose painting by numbers. Treatment as described above is feasible.
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positron emission tomography guided focal Dose escalation using intensity modulated radiotherapy for head and neck cancer
International Journal of Radiation Oncology Biology Physics, 2007Co-Authors: Indira Madani, Vincent Gregoire, Werner De Gersem, Wim Duthoy, Cristina Derie, Tom Boterberg, Mickey Saerens, Filip Jacobs, Max Lonneux, Luc VakaetAbstract:PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided Dose escalation, and to determine the maximum tolerated Dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the Dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two Dose Levels were planned: 25 Gy (Level I) and 30 Gy (Level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at Dose Level I, and 18 at Dose Level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of Dose-limiting toxicity occurred at Dose Level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at Dose Level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at Dose Levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at Dose Levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided Dose escalation appears to be well-tolerated. The maximum tolerated Dose was not reached at the investigated Dose Levels.
Xavier Mirabel - One of the best experts on this subject based on the ideXlab platform.
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phase i Dose escalation study of nbtxr3 activated by intensity modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx
European Journal of Cancer, 2021Co-Authors: Caroline Hoffmann, V Calugaru, Edith Borcoman, Victor Moreno, Emiliano Calvo, X Liem, Sebastien Salas, Bernard Doger, Thomas Jouffroy, Xavier MirabelAbstract:Abstract Purpose This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation. Methods Patients with stage III or IVA (American Joint Committee on Cancer (AJCC) guidelines, 7th edition, 2010) HNSCC of the oral cavity or oropharynx, aged ≥70 or ≥65 years and ineligible to receive cisplatin, amenable to radiotherapy (RT) with curative intent, received NBTXR3 as a single intratumoural (IT) injection followed by activation by intensity-modulated radiation therapy (IMRT; 70 Gy). The NBTXR3 Dose corresponded to a percentage of the baseline tumour volume, measured by magnetic resonance imaging. The primary objectives were to determine the recommended phase II Dose (RP2D), Dose-limiting toxicities (DLTs) and maximum tolerated Dose (MTD). Safety and tolerability were assessed using National Cancer Institute CTCAE version 4.0. Antitumour activity was assessed by Response Evaluation Criteria in Solid Tumours 1.1. Results Nineteen patients were enrolled: 3 at the Dose Level of 5%, 3 at the Dose Level of 10%, 5 at the Dose Level of 15% and 8 at the Dose Level of 22% of the tumour volume. The MTD was not reached, and no DLTs or serious adverse event (SAEs) related to NBTXR3 were observed. Four adverse events related to NBTXR3 and/or the IT injection were reported (grade I–II). NBTXR3 remained in the injected tumour throughout RT, with no leakage in the surrounding healthy tissues. Specific RT-related toxicity was as expected with IMRT. The RP2D was determined as 22% baseline tumour volume. Preliminary signs of antitumour activity were observed. Conclusion Intratumoural injection of NBTXR3 followed by IMRT is feasible and demonstrated a good safety profile, supporting further evaluation at the RP2D in this patient population. Trial registration ClinicalTrials.gov NCT01946867 .