ABSTRACT
Evidence on the efficacy of postoperative radiotherapy (PORT) in low-intermediate risk squamous cell carcinoma of the oral cavity (OSCC) remains inconclusive. Members of a task force from two national radio-oncology Associations (AIRO and GORTEC) defined 14 clinically relevant questions to identify "gray areas" pertinent to the indication for PORT in this clinical setting. Consequently, a literature review was performed on the topic. The resulting statements were then rated by an Expert Panel (EP) using a modified Delphi method. Only radiation oncologists were part of the discussion and voting on the scenarios. There was agreement on the 14 statements at the first round of voting. The task force then decided to propose clinical cases for the two more controversial statements that had received a lower agreement to better capture the Experts' attitudes. The clinical cases highlighted a more significant decisional heterogeneity. However, the good level of consensus reached among the two Associations gives relevant support in informing clinical choices while acknowledging general indications cannot fit all clinical situations and do not replace multidisciplinary discussion.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Consensus , Mouth Neoplasms/radiotherapy , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Delphi TechniqueABSTRACT
Stereotactic body radiation therapy (SBRT) has become a valid option for the treatment of low- and intermediate-risk prostate cancer. In randomized trials, it was found not inferior to conventionally fractionated external beam radiation therapy (EBRT). It also compares favorably to brachytherapy (BT) even if level 1 evidence is lacking. However, BT remains a strong competitor, especially for young patients, as series with 10-15 years of median follow-up have proven its efficacy over time. SBRT will thus have to confirm its effectiveness over the long-term as well. SBRT has the advantage over BT of less acute urinary toxicity and, more hypothetically, less sexual impairment. Data are limited regarding SBRT for high-risk disease while BT, as a boost after EBRT, has demonstrated superiority against EBRT alone in randomized trials. However, patients should be informed of significant urinary toxicity. SBRT is under investigation in strategies of treatment intensification such as combination of EBRT plus SBRT boost or focal dose escalation to the tumor site within the prostate. Our goal was to examine respective levels of evidence of SBRT and BT for the treatment of localized prostate cancer in terms of oncologic outcomes, toxicity and quality of life, and to discuss strategies of treatment intensification.
ABSTRACT
Since the development of new radiotherapy techniques that have improved healthy tissue sparing, reirradiation (reRT) has become possible. The selection of patients eligible for reRT is complex given that it can induce severe or even fatal side effects. The first step should therefore be to assess, in the context of multidisciplinary staff meeting, the patient's physical status, the presence of sequelae resulting from the first irradiation and the best treatment option available. ReRT can be performed either curatively or palliatively to treat a cancer-related symptom that is detrimental to the patient's quality of life. The selected techniques for reRT should provide the best protection of healthy tissue. The construction of target volumes and the evaluation of constraints regarding the doses that can be used in this context have not yet been fully codified. These points raised in the literature suggest that randomized studies should be undertaken to answer pending questions.
Subject(s)
Re-Irradiation , Humans , Neoplasm Recurrence, Local/radiotherapy , Quality of Life , Radiotherapy Dosage , Re-Irradiation/adverse effectsABSTRACT
INTRODUCTION: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. MATERIAL AND METHODS: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. RESULTS: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. CONCLUSION: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.
Subject(s)
Head and Neck Neoplasms , Plastic Surgery Procedures , Consensus , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Humans , Neoplasm Recurrence, Local , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/surgeryABSTRACT
BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy. METHODS: Patients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP). RESULTS: 188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64-1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78-1.81], p = 0.42). No interaction between p16 and treatment effect was found. CONCLUSION: Dose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy. Clinicaltrial.gov: NCT00158678.
Subject(s)
Head and Neck Neoplasms , Radiotherapy, Intensity-Modulated , Chemoradiotherapy , Cisplatin , Head and Neck Neoplasms/radiotherapy , Humans , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Squamous Cell Carcinoma of Head and Neck/therapyABSTRACT
During exclusive curative radiotherapy for head and neck tumors, the patient's organs at risk (OAR) and target volumes frequently change size and shape, leading to a risk of higher toxicity and lower control than expected on planned dosimetry. Adaptive radiotherapy is often necessary but 1) tools are needed to define the optimal time for replanning, and 2) the subsequent workflow is time-consuming. We designed a prospective study to evaluate 1) the validity of automatically deformed contours on the daily MVCT, in order to safely use the "dose-of the day" tool to check daily if replanning is necessary; 2) the automatically deformed contours on the replanning CT and the time gained in the replanning workflow. Forty-eight patients with T3-T4 and/or involved node >2â¯cm head and neck squamous cell carcinomas, planned for curative radiotherapy without surgery, will be enrolled. They will undergo treatment with helical IMRT including daily repositioning MVCTs. The contours proposed will be compared weekly on intermediate planning CTs (iCTs) on weeks 3, 4, 5 and 6. On these iCTs both manual recontouring and automated deformable registration of the initial contours will be compared with the contours automatically defined on the MVCT. The primary objective is to evaluate the Dice similarity coefficient (DSC) of the volumes of each parotid gland. The secondary objectives will evaluate, for target volumes and all OARs: the DSC, the mean distance to agreement, and the average surface-to-surface distance. Time between the automatic and the manual recontouring workflows will be compared.
ABSTRACT
BACKGROUND: The decision between definitive radio(chemo)therapy (RCT) or a surgical strategy, i.â¯e. surgery⯱ adjuvant radio(chemo)therapy for optimal treatment of oropharyngeal cancer is highly debated. Human papillomavirus(HPV)-related tumours are a distinct entity associated with p16 overexpression. While this represents a major prognostic factor, its predictive significance remains unknown. RESULTS: Among 183 consecutive unselected patients treated between 2009 and 2013 with a state-of-the-art surgical procedure ± adjuvant radio(chemo)therapy or definitive RCT including intensity-modulated radiotherapy, 3year disease-free survival (DFS) was 74 vs. 57%, respectively (pâ¯= 0.007). When focusing on p16+ patients (49%), there was no significant difference in tumour control rate between surgery⯱ radio(chemo)therapy and the definitive RCT group (3-year DFS 83 vs. 82%, respectively; pâ¯= 0.48). However, delayed severe dysphagia was significantly lower in favour of definitive RCT: 35 vs. 4%, respectively; pâ¯= 0.0002. CONCLUSION: Our results highlight distinct outcomes after definitive RCT or initial surgical treatment according to p16 status, which should thus be considered during the decision process.
Subject(s)
Chemoradiotherapy , Cyclin-Dependent Kinase Inhibitor p16/genetics , Decision Support Techniques , Gene Expression/genetics , Oropharyngeal Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/radiotherapy , Oropharyngeal Neoplasms/surgeryABSTRACT
PURPOSE: To evaluate image-guided Transperineal Elastic-Registration biopsy (TPER-B) in the risk-stratification of low-intermediate risk prostate cancer detected by Transrectal-ultrasound biopsy (TRUS-B) when estimates of cancer grade and volume discorded with multiparametric Magnetic Resonance Imaging (MRI). METHODS: All patients referred for active surveillance or organ-conservative management were collegially reviewed for consistency between TRUS-B results and MRI. Image-guided TPER-B of the index target (IT) defined as the largest Prostate Imaging-Reporting Data System-v2 ≥ 3 abnormality was organized for discordant cases. Pathology reported Gleason grade, maximum cancer core length (MCCL) and total CCL (TCCL). RESULTS: Of 237 prostate cancer patients (1-4/2018), 30 were required TPER-B for risk-stratification. Eight cores were obtained [Median and IQR: 8 (6-9)] including six (IQR: 4-6) in the IT. TPER-B of the IT yielded longer MCCL [Mean and (95%CI): 6.9 (5.0-8.8) vs. 2.6 mm (1.9-3.3), p < 0.0001] and TCCL [19.7 (11.6-27.8) vs. 3.6 mm (2.6-4.5), p = 0.0002] than TRUS-B of the gland. On TPER-B cores, longer MCCL [Mean and (95%CI): 8.7 mm (6.7-10.7) vs. 4.1 mm (0.6-7.6), p = 0.002] were measured in Gleason score-7 cancers. TPER-B cores upgraded 13/30 (43.3%) patients. 14/30 (46.7%) met University College London-definition 1 and 18/30 (60.0%) definition 2, which correlate with clinically significant cancers > 0.5 mL and > 0.2 mL, respectively. 7/16 (43.8%) patients under active surveillance were re-allocated toward prostatectomy (n = 5) or radiation therapy (n = 2). In 14 patients not yet assigned, TPER-B risk-stratification spurred the selection (13/14, 92.9%) of treatments with curative intent. CONCLUSION: Image-guided TPER-B of the index target provided more cancer material for pathology. Subsequent re-evaluation of cancer volume and grade switched a majority of patients towards higher-risk groups and treatments with curative intent.
Subject(s)
Image-Guided Biopsy/methods , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Grading , Perineum , Prostate/surgery , Prostatectomy , Prostatic Neoplasms/surgery , Risk Assessment , Tumor Burden , UltrasonographyABSTRACT
PURPOSE: Focal therapy of prostate cancer requires precise positioning of therapeutic agents within well-characterized index tumors (ITs). We assessed the feasibility of low-dose-rate ultrafocal brachytherapy. METHODS AND MATERIALS: The present study was an institutional review board-approved European Clinical Trials Database-registered phase II protocol. Patients referred (October 2013 to August 2016) for active surveillance (prostate-specific antigen <10 ng/mL, cT1c-cT2a, Gleason score on referring biopsy specimens ≤6 (3+3), ≤3 positive biopsy cores, ≤50% of cancer) were preselected. Inclusion was confirmed when complementary image-guided biopsy findings informed a single Prostate Imaging Reporting and Data System (PI-RADS) ≥3, Gleason score ≤7a (3+4) lesion. A ultrasound-visible ancillary marker was positioned within the IT using a magnetic resonance imaging (MRI)/3-dimensional transrectal ultrasound (TRUS) elastic fusion-guided system (Koelis). Ultrafocal transperineal delivery of 125I seeds used classic 2-dimensional TRUS (Bard-FlexFocus) and dose optimization (Variseed Treatment Planning System). Following Simon's optimal design, 17 patients were required to assess the feasibility of delivering ≥95% of the prescribed dose (160 Gy) to the IT (primary objective). Adverse events (Common Terminology Criteria for Adverse Events) and quality of life (5-item International Index of Erectile Function, International Prostate Symptom Score) were recorded. One-year control biopsy specimens were obtained from the IT and untreated segments. RESULTS: Of the 44 preselected patients, 27 did not meet the inclusion criteria. Of the 17 ultrafocal brachytherapy-treated patients, 16 met the primary objective (per protocol success). The prescription dose was delivered to 14.5% ± 6.4% of the prostate volume, resulting in negligible urethral and rectal irradiation and toxicity. No recurrence was evidenced on the 1-year follow-up MRI studies or IT biopsy specimens. Seven nonclinically significant cancers and one Gleason score 7a (3+4) cancer (salvage prostatectomy) were observed in the untreated parenchyma. CONCLUSIONS: Recent technology has allowed for selective and effective brachytherapy of small MRI targets.
Subject(s)
Brachytherapy/methods , Prostatic Neoplasms/radiotherapy , Aged , Biopsy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Grading , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Tumor BurdenABSTRACT
OBJECTIVE: To analyze the outcome of N3 patients treated with very accelerated radiotherapy (VART) or different schedules of concurrent chemoradiotherapy (CRT) within two phase III trials. PATIENTS AND METHODS: Data of 179 patients with N3 HNSCC from two GORTEC randomized trials (96-01 and 99-02) were pooled. Patients received either VART: 64.8Gy/3.5weeks or one of the 3 following CRT regimens: Conventional CRT: 70Gy/7weeks+3 cycles carboplatin-5FU; Moderately accelerated CRT: 70Gy/6weeks+2 cycles carboplatin-5FU; Strongly intensified CRT: 64Gy/5weeks+cisplatin (days 2, 16, 30) and 5 FU (days 1-5, 29-33) followed by 2 cycles adjuvant cisplatin-5FU. RESULTS: Median follow-up was 13.3 and 5.2years for GORTEC 96-01 and GORTEC 99-02, respectively. Five-year overall survival (OS) was 13.8%. No significant difference was observed between CRT versus VART in terms of OS (hazard ratio [HR]: 0.93, p=0.68), loco-regional progression (HR: 0.70, p=0.13), or distant progression (HR: 0.86, p=0.53). OS was worse for patients with T3-4 tumors versus early T stage (11.0% versus 25.7%, p=0.015). In multivariate analysis, the oropharyngeal subsite presented a higher risk of distant metastasis (as first event 46.5% vs 19.2%, p<0.001),). A significant interaction between treatment modalities and subsites has been observed concerning loco-regional and distant failures. CONCLUSION: The outcome of N3 HNSCC was extremely poor despite treatment intensification and no difference between CRT and VART. Both distant metastases and loco-regional failures remain important treatment challenge.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Head and Neck Neoplasms/therapy , Carboplatin/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Cisplatin/administration & dosage , Disease Progression , Female , Fluorouracil/administration & dosage , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Squamous Cell Carcinoma of Head and Neck , Survival AnalysisABSTRACT
PURPOSE: The purpose of this work was to retrospectively determine the value of intensity-modulated radiotherapy (IMRT) in patients with laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC), on outcome and treatment-related toxicity compared to 3-dimensional conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: A total of 175 consecutive patients were treated between 2007 and 2012 at our institution with curative intent RT and were included in this study: 90 were treated with 3D-CRT and 85 with IMRT. Oncologic outcomes were estimated using Kaplan-Meier statistics; acute and late toxicities were scored according to the Common Toxicity Criteria for Adverse Events scale v 3.0. RESULTS: Median follow-up was 35 months (range 32-42 months; 95% confidence interval 95%). Two-year disease-free survival did not vary, regardless of the technique used (69% for 3D-CRT vs. 72%; for IMRT, p = 0.16). Variables evaluated as severe late toxicities were all statistically lower with IMRT compared with 3D-CRT: xerostomia (0 vs. 12%; p < 0.0001), dysphagia (4 vs. 26 %; p < 0.0001), and feeding-tube dependency (1 vs 13%; p = 0.0044). The rates of overall grade ≥ 3 late toxicities for the IMRT and 3D-CRT groups were 4.1 vs. 41.4%, respectively (p < 0.0001). CONCLUSION: IMRT for laryngeal and hypopharyngeal cancer minimizes late dysphagia without jeopardizing tumor control and outcome.
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Deglutition Disorders/prevention & control , Hypopharyngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/radiotherapy , Radiation Injuries/prevention & control , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Radiotherapy Dosage , Radiotherapy, Adjuvant , Retrospective StudiesABSTRACT
PURPOSE: Pulsed-dose-rate (PDR) brachytherapy is thought to mimic the radiobiological benefits of continuous low-dose-rate (cLDR) delivery but is safer for medical personnel. We set out to evaluate the outcomes of this technique in patients with head and neck squamous cell carcinoma. METHODS AND MATERIALS: A total of 36 consecutive patients treated with PDR brachytherapy were randomly matched to 72 cLDR controls according to T-stage, tumor site, and management strategy. Local recurrence and late complications were compared between the two groups. RESULTS: Baseline characteristics were similar in both groups. Oral cavity cancers predominated at 81%, and 89% had T1/T2 tumors. Seventy-five percent of patients underwent surgery before radiation treatment. Median followup was 59 and 30 months for cLDR and PDR patients, respectively. Three-year actuarial local recurrence-free survival was 97% and 94% for cLDR and PDR patients, respectively (p = 0.77). Three-year cumulative risk of Grade ≥2 complications was 45% and 32% for cLDR and PDR patients, respectively (p = 0.2). For cLDR, a dose rate exceeding 68 cGy/h resulted in more complications (RR 5.3, p < 0.05). Similarly, PDR patients receiving ≥75 cGy/pulse were at higher risk. CONCLUSIONS: PDR brachytherapy in head and neck squamous cell carcinoma yields comparable results to cLDR treatment. Dose rate was correlated with the risk of late complications, regardless of technique.
Subject(s)
Brachytherapy/methods , Carcinoma, Squamous Cell/radiotherapy , Dose Fractionation, Radiation , Head and Neck Neoplasms/radiotherapy , Mouth Neoplasms/radiotherapy , Oropharyngeal Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Case-Control Studies , Clinical Protocols , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/radiotherapy , Radiotherapy Dosage , Squamous Cell Carcinoma of Head and NeckABSTRACT
PURPOSE: Recurrent head and neck cancer is associated to a poor survival prognosis. A high toxicity rate is demonstrated when surgery and/or radiotherapy and/or chemotherapy are combined. Furthermore, the duration of treatment is often not ethically compatible with the expected survival (median survival<1year). Normal tissues tolerance limits the use of reirradiation and stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. After completion of a feasibility study, results of a multicentric study (Lille, Nancy & Nice) using SBRT with cetuximab are reported. The aim of the study was to deliver non toxic short course SBRT (2weeks) in order to get the same local control as the one demonstrated with longer protocols. METHODS AND MATERIALS: Patients with inoperable recurrent, or new primary tumor in a previously irradiated area, were included (WHO<3). Reirradiation (RT) dose was 36Gy in six fractions of 6Gy to the 85% isodose line covering 95% of the PTV with 5 injections of concomitant cetuximab (CT). All patients had previous radiotherapy, 85% had previous surgery and 48% previous chemotherapy. RESULTS: Between 11/2007 and 08/2010, 60 were included (46 men and 14 women), 56 received CT+RT, 3 were not treated and 1 received only CT. Median age was 60 (42-87)) and all 56 patients had squamous carcinoma and received concomitant cetuximab. Mean time between previous radiotherapy and the start of SBRT was 38months. Cutaneous toxicity was observed for 41 patients. There was one toxic death from hemorrhage and denutrition. Median follow-up was 11.4months. At 3months, response rate was 58.4% (95% CI: 43.2-72.4%) and disease control rate was 91.7% (95% CI: 80.0-97.7%). The one-year OS rate was 47.5% (95% CI: 30.8-62.4). CONCLUSION: These results suggest that short SBRT with cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. This combination may be the reference treatment is this population.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , ErbB Receptors/antagonists & inhibitors , Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Radiosurgery , Adult , Aged , Aged, 80 and over , Cetuximab , Combined Modality Therapy , Female , Head and Neck Neoplasms/mortality , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Salvage TherapyABSTRACT
PURPOSE: To review the clinical outcome of I-125 permanent prostate brachytherapy (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2 techniques of loose-seed implantation. METHODS AND MATERIALS: 574 consecutive patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer between 2000 and 2008. Two successive techniques were used: conventional implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED) survival results were reported and compared for the 2 techniques. Univariate and multivariate analysis researched independent predictors for bNED survival. RESULTS: 419 (73%) and 155 (27%) patients with low-risk and intermediate-risk disease, respectively, were treated (median follow-up time, 69.3 months). The 60-month bNED survival rates were 95.2% and 85.7%, respectively, for patients with low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients treated with automated implantation had worse bNED survival rates than did those treated with conventional implantation (P<.0001). By day 30, patients treated with automated implantation showed lower values of dose delivered to 90% of prostate volume (D90) and volume of prostate receiving 100% of prescribed dose (V100). In multivariate analysis, implantation technique, Gleason score, and V100 on day 30 were independent predictors of recurrence-free status. Grade 3 urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort, respectively, with no significant differences between the 2 techniques. No grade 3 proctitis was observed. CONCLUSION: Satisfactory 60-month bNED survival rates (93.1%) and acceptable toxicity (grade 3 urethritis<3%) were achieved by loose-seed implantation. Automated implantation was associated with worse dosimetric and bNED survival outcomes.
Subject(s)
Brachytherapy/methods , Prostatic Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Analysis of Variance , Brachytherapy/adverse effects , Follow-Up Studies , Humans , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/mortality , Radiotherapy Dosage , Survival Rate , Urethritis/etiology , Urethritis/pathology , Urinary Incontinence/etiologyABSTRACT
PURPOSE: To assess residual setup errors during head and neck radiation therapy and the resulting consequences for the delivered dose for various patient alignment procedures. METHODS AND MATERIALS: Megavoltage cone beam computed tomography (MVCBCT) scans from 11 head and neck patients who underwent intensity modulated radiation therapy were used to assess setup errors. Each MVCBCT scan was registered to its reference planning kVCT, with seven different alignment procedures: automatic alignment and manual registration to 6 separate bony landmarks (sphenoid, left/right maxillary sinuses, mandible, cervical 1 [C1]-C2, and C7-thoracic 1 [T1] vertebrae). Shifts in the different alignments were compared with each other to determine whether there were any statistically significant differences. Then, the dose distribution was recalculated on 3 MVCBCT images per patient for every alignment procedure. The resulting dose-volume histograms for targets and organs at risk (OARs) were compared to those from the planning kVCTs. RESULTS: The registration procedures produced statistically significant global differences in patient alignment and actual dose distribution, calling for a need for standardization of patient positioning. Vertically, the automatic, sphenoid, and maxillary sinuses alignments mainly generated posterior shifts and resulted in mean increases in maximal dose to OARs of >3% of the planned dose. The suggested choice of C1-C2 as a reference landmark appears valid, combining both OAR sparing and target coverage. Assuming this choice, relevant margins to apply around volumes of interest at the time of planning to take into account for the relative mobility of other regions are discussed. CONCLUSIONS: Use of different alignment procedures for treating head and neck patients produced variations in patient setup and dose distribution. With concern for standardizing practice, C1-C2 reference alignment with relevant margins around planning volumes seems to be a valid option.
Subject(s)
Anatomic Landmarks/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Patient Positioning , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Setup Errors , Radiotherapy, Image-Guided/methods , Radiotherapy, Intensity-Modulated/methods , Cervical Vertebrae/diagnostic imaging , Cone-Beam Computed Tomography , Head and Neck Neoplasms/diagnostic imaging , Humans , Mandible/diagnostic imaging , Maxillary Sinus/diagnostic imaging , Organs at Risk/diagnostic imaging , Radiotherapy Dosage , Sphenoid Sinus/diagnostic imaging , Thoracic Vertebrae/diagnostic imagingABSTRACT
Radiotherapy is an integral part of overall cancer therapy. One of the most serious adverse effects of irradiation concern, for long-term survivors, the development of post-radiation sarcoma (PRS) in healthy tissues located within the irradiated area. PRS have bad prognosis and are often detected at a late stage. Therefore, it is obvious that the early detection PRS is a key-point and the development of preclinical models is worthy to evaluate innovative diagnostic and therapeutic procedures. The aim of this study was to develop a spontaneous rodent model of PRS and to evaluate the potency of Positron Emission Tomography (PET) for early detection. Fifteen Wistars rats were irradiated unilateraly on the hindlimb with a single dose of 30 Gy. Sequential analysis was based on observational staging recordings, Computerized Tomography (CT) scanning and PET. Tumors were removed and, histopathological and immunochemistry analyses were performed. Among the irradiated rats, 12 sarcomas (80%) were detected. All tumors occurred naturallty within the irradiated hindlimb and were highly aggressive since most tumors (75%) were successfully transplanted and maintained by serial transplantation into nude mice. Upon serial staging recordings, using PET, was found to enable the detection of PRS earlier after irradiation than with the other methods (i.e. 11.9 ± 1.8 vs 12.9 ± 2.6 months). These results confirmed the interest of experimental models of PRS for the preclinical evaluation of innovative diagnostic strategies and confirmed the potency of PET for early detection of PRS. This preclinical model of PRS can also be proposed for the evaluation of therapeutic strategies.
Subject(s)
Models, Animal , Neoplasms, Radiation-Induced/diagnostic imaging , Positron-Emission Tomography , Sarcoma, Experimental/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Animals , Biomarkers, Tumor/analysis , Cobalt Radioisotopes , Early Diagnosis , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Hindlimb , Male , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasm Transplantation , Neoplasms, Radiation-Induced/pathology , Radiopharmaceuticals , Rats , Rats, Wistar , Sarcoma, Experimental/etiology , Sarcoma, Experimental/pathology , Soft Tissue Neoplasms/etiology , Soft Tissue Neoplasms/pathology , Tomography, X-Ray ComputedABSTRACT
BACKGROUND AND PURPOSE: In 2003, the French Authority for Health (HAS) recommended the use of intensity modulated radiotherapy (IMRT) in prospective trial before its routine use. The Oncology and Radiotherapy Group for Head and Neck Cancer (GORTEC) proposed to evaluate prospectively acute and late toxicities, locoregional control and overall survival for patients treated for head and neck cancer (HNC) with IMRT and bilateral neck irradiation. MATERIALS AND METHODS: Between 2002 and 2008, 208 patients with HNC were treated with IMRT in 8 centres. There were 38 nasopharynx, 117 oropharynx, 25 pharyngo-larynx, 24 oral cavity and 4 unknown primary (28.5% stage I-II and 71% Stage III-IV). Ninety-three patients (46%) had postoperative IMRT and 78 patients (37.5%) received concurrent chemotherapy. The doses were 70 Gy to the gross tumour, 66 Gy to the high-risk postoperative sites and 50 Gy to the subclinical disease. Toxicities were graded according to the RTOG-EORTC scales. RESULTS: The median follow-up was 25.3 months (range: 0.4-72 months). There were 29 local-regional failures: 24 were in-field, three were marginal and one was out-field. The two-year loco-regional control and overall survival were 86% and 86.7%, respectively. At 18 months, grade ≥ 2 xerostomia was 16.1%. A mean dose to the spared parotid below 28 Gy led to significantly less grade ≥ 2 xerostomia (8.5% vs 24%) with a relative risk of 1.2 [95% CI: 1.02-1.41, p = 0.03]. Grade ≥ 2 xerostomia increased by approximately 3% per Gy of mean parotid dose up to 28, Gy then 7% per Gy above 33 Gy. CONCLUSIONS: IMRT for HN cancer seems to reduce late toxicities without jeopardising local control and overall survival.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated , Adolescent , Adult , Aged , Aged, 80 and over , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Neoplasm Grading , Prospective Studies , Radiotherapy, Intensity-Modulated/adverse effects , Xerostomia/etiologyABSTRACT
BACKGROUND: Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. METHODS: In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. FINDINGS: Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). INTERPRETATION: Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. FUNDING: French Ministry of Health.
Subject(s)
Carcinoma/therapy , Chemoradiotherapy/methods , Head and Neck Neoplasms/therapy , Adult , Aged , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Patient Safety , Treatment OutcomeABSTRACT
PURPOSE: To determine if image-guided radiotherapy (IGRT) ensures dose coverage to the target, and to assess the dosimetric impact of anatomic changes using megavoltage cone-beam CT (MVCBCT) for patient positioning during head and neck IMRT. METHODS AND MATERIALS: Forty-eight MVCBCT from 10 head and neck IMRT/IGRT patients were analyzed off-line. Target volumes and organs at risk (OARs) contours delineated on CT were transferred and adjusted on MVCBCT images. Each MVCBCT was processed to allow dose recalculation, resulting in 469 dose-volume histograms (DVHs). The concept of dosimetric latitude was introduced to provide a clinical perspective. RESULTS: MVCBCT target DVHs showed a moderate level of difference in D95 (dose to ≥95% of volume), generally less than a 5% difference from the planned dose. Delivered-dose increases to the spinal cord and brainstem showed no apparent time trend. The 4mm margin around OARs was a useful precaution to prevent exceeding critical dose thresholds. The parotid glands showed progressive increases in mean dose related to shrinkage of the external contours. CONCLUSION: IGRT repositioning ensured target volume coverage, but significant dose variations were observed for OARs. The dosimetric impact of anatomic changes during radiotherapy was of lesser importance than the effects of IGRT repositioning.
Subject(s)
Cone-Beam Computed Tomography/methods , Head and Neck Neoplasms/radiotherapy , Radiotherapy, Image-Guided , Radiotherapy, Intensity-Modulated , Head and Neck Neoplasms/pathology , Humans , Patient Positioning , Radiotherapy Dosage , Tumor BurdenABSTRACT
BACKGROUND: We aimed to explore (i) the short-term retention of intramedullary implanted mesenchymal stem cells BMSCs and (ii) their impact on the bone blood flow and metabolism in a rat model of hindlimb irradiation. METHODS: Three months after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham-operated group (n = 6) and a treated group (n = 8) in which ¹¹¹In-labelled BMSCs (2 × 106 cells) were injected in irradiated tibias. Bone blood flow and metabolism were assessed by serial (99m)Tc-HDP scintigraphy and 1-wk cell retention by recordings of (99m)Tc/¹¹¹In activities. RESULTS: The amount of intramedullary implanted BMSCs was of 70% at 2 H, 40% at 48 H, and 38% at 168 H. Bone blood flow and bone metabolism were significantly increased during the first week after cell transplantation, but these effects were found to reduce at 2-mo followup. Conclusion. Short-term cell retention produced concomitant enhancement in irradiated bone blood flow and metabolism.