Simultaneous Modulated Accelerated Radiation Therapy Research Articles

Simultaneous Modulated Accelerated Radiotherapy (SMART) with Dysphagia Aspiration-Related Structures (DARS) Sparing: Do We Have a Role for Dose Condensation in Locally Advanced Head and Neck Cancer

Introduction Concurrent chemotherapy integrated with intensity-modulated radiotherapy (IMRT) is the standard of care for locally advanced head and neck cancer. Simultaneous integrated boost technique has allowed differential doses to primary and normal structures permitting significant toxicity reduction. The current study explores the feasibility of the simultaneous modulated accelerated radiotherapy (SMART) technique to enhance cytoreduction and explore the possibility of dose intensification with radiobiologically targeted treatment condensation. Methods Thirty patients were randomized in an open-labeled study to receive concurrent chemoradiation of 60 Gy in 25 fractions with “SMART” technique or 70 Gy in 35 fractions using conventional intensity-modulated radiotherapy simultaneous integrated boost “IMRT SIB.” The primary endpoints included comparative volumetric cytoreduction between the study and control arm assessed during the course of treatment and final response evaluation. Secondary endpoints involved the assessment of acute toxicity parameters for xerostomia, mucositis, dysphagia, and fatigue. Results The “SMART” study arm showed comparable volumetric cytoreduction to the conventional “IMRT SIB” arm at midtreatment (p-value = 0.225) as well as toward completion (p-value = 0.476). The study arm did observe 94.4% cytoreduction of tumor volume compared with 88.05% in the conventional arm at the time of response evaluation. In spite of treatment condensation, there was no significant increase in toxicity with “SMART.” There was no difference in the frequency or duration of grade 3 mucositis in the “SMART” arm in spite of intensification (p-value = 0.728). In the “SMART” arm, there was a favorable reduction in the duration of grade ⅔ dysphagia; 2.8 weeks versus 4.6 weeks (p-value = 0.002). Even though the xerostomia was comparable in frequency and intensity, the total duration of xerostomia was 50% less (p-value = 0.001). Conclusions The “SMART” technique provides a radiobiologically sound, effective, and safe protocol that has the potential to improve the treatment of locally advanced head and neck cancer. The good tolerability and toxicity profile in the study arm is encouraging and facilitates further research.

A Prospective Phase II Study of Simultaneous Modulated Accelerated Radiotherapy Concurrently With CDDP/S1 for Esophageal Squamous Cell Carcinoma in the Elderly.

BackgroundTo explore the efficacy and toxicity of simultaneous modulated accelerated radiotherapy (SMART) concurrently with cisplatin (CDDP) and S1 (tegafur/gimeracil/oteracil) in elderly patients with esophageal squamous cell carcinoma (ESCC).MethodsThis single-arm, phase II study enrolled pathologically confirmed, stage II–IVa ESCC of 70–80 years old and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients received SMART (64 Gy to gross tumor volume and 48 Gy to clinical target volume in 30 fractions) with concurrent CDDP (day 1 of each week) and S1 (days 1–14, 22–35). The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicities.ResultsThirty-seven eligible patients were analyzed with median follow-up of 25.7 months for all and 46.1 months for survivors. The ORR was 88.9%. Patients with baseline weight loss <5% (p=0.050) and nutritional risk index (NRI) ≥105.2 (p=0.023) had better tumor response. Median PFS was 13.8 months with 2-year PFS of 37.5%. Median OS was 27.7 months with 2-year OS of 57.5%. OS was significantly associated with ECOG PS (p=0.005), stage (p=0.014), gross tumor volume (p=0.004), baseline NRI (p=0.036), baseline C-reactive protein (CRP) level (p=0.003) and tumor response (p=0.000). CRP level (p=0.016) and tumor response (p=0.021) were independently prognostic of OS. ≥grade 3 anemia, neutropenia and thrombocytopenia occurred in 2.7%, 10.8% and 13.5% of patients; ≥grade 3 esophagitis and pneumonitis occurred in 18.9% and 2.7% of patient, respectively.ConclusionSMART concurrently with CDDP/S1 yielded satisfactory response rate, survival outcome and tolerable treatment-related toxicities in elderly patients with ESCC. Further studies are warranted to validate the results.

Induction Chemotherapy Plus Simultaneous Modulated Accelerated Radiation Therapy in Non-operative Hypopharyngeal and Supraglottic Laryngeal Squamous Cell Carcinoma: Long-Term Outcome of a Prospective Phase 2 Study.

Background: To evaluate the toxicities and long-term outcomes of induction chemotherapy (ICT) plus simultaneous modulated accelerated radiation therapy (SMART) in non-operative hypopharyngeal and supraglottic laryngeal squamous cell carcinoma (SCCH/L).Materials and Methods: This was a prospective phase 2 study. Patients diagnosed with SCCH/L, aged from 18 to 75, staged from III to IVB in accordance with the AJCC 2010 criteria, and refusing surgery were eligible. The patients were treated with 2–3 cycles of docetaxel-cisplatin-based ICT and SMART combined with 2–3 cycles of cisplatin-based concurrent chemotherapy. The prescription dose to the primary tumor and metastatic nodes was 69 Gy in 30 fractions. Acute and late toxicities were assessed according to the established Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and long-term outcomes were analyzed.Results: Between February 2013 and June 2015, 55 newly diagnosed SCCH/L patients were enrolled. No grade 2 or worse acute xerostomia was noted. The incidences of grade 3 acute dermatitis, oral mucositis, and pharyngoesophagitis were 12.7, 3.6, and 12.7%, respectively. The median follow-up time was 48 months (range 5.5–74 months). The main late toxicity was hoarseness or sore throat, with an incidence of 32.7%. The 5-year functional larynx-preservation survival was 51.5%. The 3- and 5-year locoregional control and overall survival were 58.2, 51.5, 63.6, and 54.1%, respectively.Conclusions: The ICT plus SMART with a regimen of 69 Gy/30 F for the treatment of SCCH/L demonstrated acceptable severe toxicity, satisfactory long-term outcomes, and laryngeal function preservation.

Efficacy of Function-Adapted Simultaneous Modulated Accelerated Radiation Therapy (FA-SMART) with Concurrent Chemotherapy in Patients with Locally Advanced Non–Small-Cell Lung Cancer: A Phase 2 Prospective Clinical Trial

To determine whether the function-adapted simultaneous modulated accelerated radiation therapy (FA-SMART) technique and concurrent weekly chemotherapy can improve treatment efficacy in patients with locally advanced non-small-cell lung cancer (NSCLC). In this single-arm phase 2 study (clinicaltrials.gov Identifier: NCT02573506), we enrolled patients with unresectable stage III NSCLC and an Eastern Cooperative Oncology Group performance status score of 0-1. Split-course thoracic radiotherapy was delivered using FA-SMART technique. Pulmonary function test (PFT) including the percentage-predicted forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC %) and single-breath carbon monoxide diffusing capacity (DLCO %) was performed at baseline and after the interval. Patients were irradiated at 51Gy in 17 daily fractions in the first course. After the interval, patients who had non-progressive disease and an adequate pulmonary function (FEV1/FVC % ≥ 40% and DLCO % ≥ 45%) underwent adaptive re-planning, and were irradiated at 15∼18Gy in 5∼6 daily fractions as a boost. Concurrent chemotherapy consisted of weekly docetaxel and nedaplatin. The primary endpoint was progression-free survival (PFS). The Kaplan-Meier method and log-rank tests were performed for survival analysis. Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0). A total of 89 patients were enrolled and analyzed. Eighty-three patients (93.3%) completed two courses of RT at a total dose of 66∼69Gy. The median follow-up was 26 months (range, 12∼51 months) on living patients. Median PFS was 12.0 months (95% CI, 7.8∼16.2 months) and the PFS rates were 47.8% (95% CI, 37.2∼58.4%) at 1 year and 35.0% (95% CI, 24.0∼46.0%) at 3 years. Median OS was 27.0 months (95% CI, 14.3∼39.7 months) and the OS rates were 74.2% (95% CI, 65.2∼83.2%) at 1 year and 43.1% (95% CI, 30.6∼55.6%) at 3 years. Grade ≥3 acute esophagitis was observed in 15(16.9%) patients. Grade ≥3 acute and late pneumonitis was observed in 7(7.9%) and 3(3.3%) patients respectively. DLCO was significantly reduced after the first course of RT (6.62 vs 5.79 mmol/min/kPa, p = 0.016). Patients with better interval DLCO % had significantly better OS (DLCO % ≥80% vs 60-79% vs 45-59% vs <45%, 2-year OS was 72.4% vs 45.3% vs 42.1% vs 0, p = 0.008). Interval DLCO % also correlated significantly with the incidence of grade 3 acute pneumonitis (p = 0.005). The split-course FASMART with concurrent chemotherapy has apparently improved survival with no loss in palliation or increased morbidity in patients with LANSCLC. PFT, DLCO in particular, is a necessary indicator for evaluation of irradiation boost after interval. Patients with favorable lung function after treatment interval would benefit more from intensive CCRT regimen, which should be taken into account for future study design.

Clinical study on simultaneous modulated accelerated radiotherapy for advanced cervical cancer

Objective To study the clinical efficiency and adverse reactions of simultaneous modulated accelerated radiotherapy (SMART) and intensity-modulated radiation therapy (IMRT) in advanced cervical cancer. Methods Sixty patients with advanced cervical cancer were collected from April 2011 to April 2017 in our hospital. The 60 patients were randomly divided into experimental group (30 cases) and control group (30 cases) by using stratified randomization method. The two groups were given intracavitary irradiation and concurrent chemotherapy. The patients in experimental group were treated with SMART and the patients in control group were treated with IMRT. 95% planned target volume was 50.4 Gy/28 F in the two groups and the dose for IMRT with simultaneous integrated boost was 64.4 Gy/28 F to the planning target volume. Disease progression, survival time and adverse reactions of the two groups were compared. Results At the end of radiothe-rapy, the experimental group had 23 patients with complete response (CR), 4 patients with partial response (PR), 2 patients with unaltered stable disease (SD), 1 patient with progressive disease (PD), and the control group had 22 patients with CR, 3 patients with PR, 3 patients with SD, 2 patients with PD. The overall efficiency of the experimental group was slightly higher than that of the control group (90.0% vs. 83.3%), but the difference was not statistically significant (χ2=0.144, P=0.704). After 3 months of radiotherapy, the experimental group had 28 patients with CR, 1 patient with PR, 1 patient with PD, and the control group had 22 patients with CR, 2 patients with PR, 3 patients with SD, 3 patients with PD. The overall efficiency of the experimental group (96.7%) was higher than that of the control group (96.7% vs. 80.0%), but the diffe-rence was not statistically significant (χ2=2.588, P=0.108). The median overall survival time of the experimental group and control group were 43 months and 38 months, and the difference was statistically significant (χ2=7.087, P=0.008). The 1-year survival rates of the two groups were 96.6% and 85.7%, and the 3-year survival rates were 86.2% and 60.7%, respectively. There were no significant differences in the incidences of gastrointestinal reaction (66.7% vs. 63.3%, χ2=0.073, P=0.787), urinary system reaction (33.3% vs. 30.0%, χ2=0.077, P=0.781) and bone marrow suppression (83.3% vs. 86.7%, χ2=0.000, P=1.000) between the two groups. Conclusion The efficiency of advanced cervical cancer patient treated with SMART is better than IMRT, and the adverse reactions are tolerable, which is worthy of clinical promotion. Key words: Uterine cervical neoplasms; Radiotherapy, intensity-modulated; Simultaneous modulated accelerated radiotherapy; Adverse reaction

Optimized radiotherapy to improve clinical outcomes for locally advanced lung cancer

BackgroundWe aimed to evaluate the toxicity, loco-regional control (LRC) and overall survival (OS) associated with accelerated intensity-modulated radiotherapy (IMRT) for locally advanced lung cancer.MethodsSeventy-three patients were consecutively treated with IMRT from November 2011 to August 2016. A total dose of 66 Gy was delivered using two different schedules of radiotherapy: simultaneous modulated accelerated radiotherapy (SMART) (30 × 2.2 Gy, across 6 weeks) with or without chemotherapy, or moderate hypofractionated radiotherapy (HRT) (24 × 2.75 Gy, across 4 weeks) in patients unfit to receive concomitant chemotherapy. Data on esophageal and pulmonary toxicities, LRC and OS were prospectively collected.ResultsThe median follow-up duration was 44 months. Severe pneumonitis and esophagitis (grade 3–4) were observed in 7% and 1% of patients respectively, with only one case of grade 4 (pneumonitis). Overall, the 1-year and 2-year LRCs were 76% [95 confidence interval (CI)%: 66–87%] and 62% [95 CI%: 49–77%] respectively. The 1 and 2-year OS rates were 72% [95% CI: 63–83%] and 54% [95 CI%: 43–68%] respectively. None parameters were correlated with LRC or OS. In particular, no difference was observed between patients treated with SMART and H-RT (p = 0.26 and 0.6 respectively), with a 1-year LRC of 74% [95 CI%: 62–86%] for SMART and 91% [95 CI%: 74–100%] for H-RT. No significant differences were observed in the toxicity rates associated with each of the RT schedules.ConclusionsAccelerated IMRT for locally advanced lung cancer is associated with low toxicities and high LRC. Moderate hypofractionated RT, by decreasing the total treatment time, may be promising in improving clinical outcomes.

Randomized controlled study comparing simultaneous modulated accelerated radiotherapy versus simultaneous integrated boost intensity modulated radiotherapy in the treatment of locally advanced head and neck cancer

ObjectivesComparison of two fractionation schedules of intensity modulated radiotherapy (IMRT) for locally advanced head and neck cancer – simultaneous integrated boost (SIB-IMRT) and simultaneous modulated accelerated radiotherapy (SMART) boost in terms of toxicity and survival end-point measures. Patients and methodsSixty patients with locally advanced head and neck cancer were randomized in two treatment arms (SIB-IMRT [control arm] and SMART boost arm [study arm]). In the control arm, patients received 70, 63 and 56 Gy in 35 fractions to clinical target volumes (CTV) 1, 2 and 3, respectively. In the study arm, patients received 60 and 50 Gy to CTV 1 and CTV 3, respectively. Toxicities, progression free survival (PFS) and overall survival (OS) were compared between both arms. ResultsBaseline patient-related characteristics were comparable between the arms except for primary site of tumour. No significant differences were noted in acute toxicities between the arms except for fatigue which was statistically higher for control arm. No significant differences in 2-year late toxicities were observed. The median follow-up duration was 25.5 (range, 1.8–39.9) months. The 2-year PFS was 53.3% and 80.0% (p = 0.028) for control and study arm, respectively. The 2-year OS was 60.0% and 86.7% (p = 0.020) in control and study arms, respectively. Multivariate analysis showed clinical stage and site to be significant predictors for OS and PFS, respectively. ConclusionsThe SMART boost technique can be a feasible alternative fractionation schedule that reduces the overall treatment time, maintaining comparable toxicity and survival compared with SIB-IMRT.

Induction Chemotherapy Plus Simultaneous Modulated Accelerated Radiation Therapy in Non-operative Hypopharyngeal and Supraglottic Laryngeal Squamous Cell Carcinoma: Preliminary Results of a Prospective Phase 2 Study

To evaluate the toxicities and short-term outcome of induction chemotherapy (ICT) plus high biological effective dose (BED) simultaneous modulated accelerated radiotherapy (SMART) in non-operative hypopharyngeal and supraglottic laryngeal squamous cell carcinoma (SCCH/L). Patients diagnosed SCCH/L, aged from 18 to 75, either staged retrospectively from III to IV B, in accordance with the AJCC 2010 criteria,or refused operation were eligible. The patients were treated with 2 cycles of docetaxel-cisplatin based ICT, and 2-3 cycles cisplatin-based concurrent chemotherapy combined SMART.The prescription dose of pGTV was 69 Gy, in 30 fractions, 2.30 Gy per fraction.The BED is equivalent to 70Gy, in 33 fractions, 2.12 Gy per fraction.This study began enrolling patients since February 2013,and was registered with number ChiCTR-ONRC-14004240. Between February 2013 and June 2015, 60 newly diagnosed SCCH/L patients were enrolled. Xerostomia > grade 2 was not noted. The incidences of grade 3 skin reaction, oral mucositis and pharyngo-esophagitis were low, 11.7%(7/60), 3.3% (2/60) and 11.7% (7/60),respectively.Two patients had tracheotomy due to severe larynx toxicity. The main adverse reaction was hoarseness or sore throat, the incidence was 30% (18/60).Biopsy confirmed radiation injury in 3 cases.The 1-and 2-year local control rates(LC), progression free survival (PFS) and overall survival (OS) was 90.0% and 70.5%,90.0% and 70.7%, 90.0% and 71.9%,respectively.Patients with severe pharyngo-esophagitis had poor prognosis,it was independent factor of OS(p=0.03,95%CI 1.104-7.202). The ICT plus SMART regimen of 69Gy/30f in the treatment of SCCH/L demonstrated minor severe toxicities and satisfied short-term outcome.But we should pay attention to choose the appropriate crowd with high BED radiotherapy.

Propensity score matching analysis of a phase II study on simultaneous modulated accelerated radiation therapy using helical tomotherapy for nasopharyngeal carcinomas

BackgroundUsing propensity score matching method (PSM) to evaluate the feasibility and clinical outcomes of simultaneous modulated accelerated radiation therapy (SMART) using helical tomotherapy (HT) in patients with nasopharyngeal carcinoma (NPC).MethodsBetween August 2007 and January 2016, 381 newly diagnosed NPC patients using HT were enrolled in pre-PSM cohort, including 161 cases in a prospective phase II study (P67.5 study, with a prescription dose of 67.5Gy in 30 fractions to the primary tumour and positive lymph nodes) and 220 cases in a retrospective study (P70 study, with a prescription dose of 70Gy in 33 fractions to the primary tumour and positive lymph nodes). Acute and late toxicities were assessed according to the established RTOG/EORTC criteria and Common Terminology Criteria for Adverse Events (CTCAE) V 3.0. Survival rate were assessed with Kaplan-Meier method, log-rank test and Cox regression.ResultsAfter matching, 148 sub-pairs of 296 patients were generated in post-PSM cohort. The incidence of grade 3–4 leukopenia, thrombocytopenia and anemia in the P67.5 group was significantly higher than in the P70 study, but no significant different was found in other acute toxicities or late toxicities between the two groups. The median follow-up was 33 months in the P67.5 and P70 group, ranging 12–54 months and 6–58 months, respectively. No significant differences in 3-year local-regional recurrence free survival (LRRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were observed between the 2 groups. Univariate analysis showed that age, T stage, clinical stage were the main factors effecting survival. Cox proportional hazards model showed that 67.5Gy/30F pattern seemed superior in 3-year OS (HR = 0.476, 95% CI: 0.236-0.957).ConclusionsThrough increasing fraction dose and shortening treatment time, the P67.5 study achieved excellent short-term outcomes and potential clinical benefits, with acceptable acute and late toxicities.Trial registrationThe trial was registered at Chinese Clinical Trial Registry on 5 July 2014 with a registration code of ChiCTRONC-14,004,895.

Radiotherapy of nasopharyngeal cancer using Rapidarc: dosimetric study of military teaching hospital Mohamed V, Morocco

BackgroundThe aim of the present study is to assess efficacy and efficiency of Volumetric-modulated arc therapy (VMAT) technique in treatment of nasopharyngeal cancer in our institution and to report toxicity related to this technique.MethodsBetween June 2013 and January 2015, thirty-two patients with non metastatic nasopharyngeal cancer were curatively treated using VMAT Rapidarc. Dose prescription was performed using two different schedules, it consisted of either simultaneous integrated boost or simultaneous modulated accelerated radiation therapy delivering 70 Gy in 35 fractions and 69.96 in 33 fractions respectively. The choice was leaved at the discretion of the treating physician. The optimization process was performed by Eclipse software version 10.0 (Varian Medical Systems), using PRO algorithm (Progressive resolutive optimisation) version 3. Data was collected from dose-volume histograms for both planning target volumes (PTV) and organs at risk (OAR). We calculated the homogeneity index and the conformity index as well as the number of monitor units MU and the treatment delivery time. We also reported acute and late toxicity related to radiation therapy.ResultsFor the PTV high risk (HR), intermediate risk (PTV IR) and low risk (LR) the D95% was 97.21 ± 1.5, 97.5 ± 3.3 and 97.10 ± 6.86 respectively. Whereas, The D5% was 104.6 ± 2.16, 103.8 ± 2.1 and 100.89 ± 7.26. The CI for PTV HR was 0.98 ± 0.02 and the HI was 0.08 ± 0.02. The mean treatment delivery time was 2.3 ± 0.2, and the mean MU number was 527.6 ± 131.4. Grade 4 toxicity was not reported in any case. Grade 3 xerostomia was observed in only 3(9.4%) patients and no patients developed grade 3 hearing loss.ConclusionOur results confirmed the abilities of VMAT to provide excellent coverage of target volumes while sparing OAR especially the nervous structures and salivary glands.

Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study.

BackgroundThe aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART) delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC).MethodsBetween August 2011 and September 2013, 132 newly diagnosed NPC patients were enrolled for a prospective phase II study. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 67.5 Gy (2.25 Gy/F), 60 Gy (2.0 Gy/F), and 54 Gy (1.8 Gy/F), in 30 fractions, respectively. Acute toxicities were evaluated according to the established RTOG/EORTC criteria. This group of patients was compared with the 190 patients in the retrospective P70 study, who were treated between September 2004 and August 2009 with helical tomotherapy, with a dose of 70-74 Gy/33F/6.5W delivered to pGTVnx and pGTVnd.ResultsThe median follow-up was 23.7 (12–38) months. Acute radiation related side-effects were mainly problems graded as 1 or 2. Only a small number of patients suffered from grade 4 leucopenia (4.5%) or thrombocytopenia (2.3%). The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), local-nodal relapse-free survival (LNRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.7%, 95.5%, 92.2%, 92.7% and 93.2%, at 2 years, respectively, with no significant difference compared with the P70 study.ConclusionsSmart delivered via the helical tomotherapy technique appears to be associated with an acceptable acute toxicity profile and favorable short-term outcomes for patients with NPC. Long-term toxicities and patient outcomes are under investigation.

Simultaneous modulated accelerated radiotherapy in cervical cancer with retroperitoneal lymph node metastasis after radical hysterectomy and pelvic lymphadenectomy.

To compare the dosimetry, toxicity, and efficacy of simultaneous modulated accelerated radiotherapy (SMART) with 3-dimensional conformal radiotherapy (3DCRT) in cervical cancer with retroperitoneal lymph node metastasis after radical hysterectomy and pelvic lymphadenectomy. Total 32 patients who underwent SMART were retrospectively evaluated. Daily fractions of 2.2 to 2.4 Gy and 1.8 to 2 Gy were prescribed and delivered to gross tumor volume and clinical target volume to a total dose of 63.8 and 52.2 Gy, respectively. A 3DCRT plan was designed for the SMART group and planned to deliver the same prescribed dose. The doses of organs at risk (OARs) were compared. Thirty-six patients who received 3DCRT were used to compare the target dose, toxicities, and efficacy with 32 cases who received SMART. The mean doses delivered to gross tumor volume and clinical target volume were significantly higher in the SMART group than in the 3DCRT group (63.8 vs 55.2 Gy [P < 0.01] and 52.5 vs 48.6 Gy [P < 0.01], respectively). For SMART plan, the doses of OARs were significantly lower than that of 3DCRT plans (small intestine: 25.1 vs 30.9 Gy [P < 0.01], bladder: 35.3 vs 46.3 [P < 0.01], and rectum: 31.7 vs 43.7 [P = 0.002], respectively). The patients experienced less acute and late toxicities in the SMART group (acute toxicities: enteroproctitis, P = 0.019; cystitis, P = 0.013; leukopenia, P = 0.025; late toxicities: enteroproctitis, P = 0.007; and cystitis, P = 0.026, respectively). No significant difference was found for 1-year survival (78.7% vs 67.7%, P = 0.222), but SMART group had a higher 2-year survival rate (2-year: 63.1% vs 39.1%, P = 0.029). Simultaneous modulated accelerated radiotherapy plans yielded higher dose to the targets and better sparing of OARs than did 3DCRT in cervical cancer with retroperitoneal lymph node metastasis after radical hysterectomy and pelvic lymphadenectomy. Simultaneous modulated accelerated radiotherapy provided better clinical outcomes than did 3DCRT. Long-term follow-up and studies involving more patients are needed to confirm our results.

Analysis of simultaneous modulated accelerated radiotherapy (SMART) for nasopharyngeal carcinomas

The purpose of this study was to analyze the clinical outcomes of simultaneous modulated accelerated radiotherapy (SMART) in patients with nasopharyngeal carcinoma (NPC). A total of 97 patients who underwent SMART for NPC between August 2005 and November 2011 were evaluated. The prescribed dose was 69.9 Gy/30 fractions at 2.33 Gy/fraction to the primary gross tumor volume (PGTV) including the nasopharynx gross target volume and the positive neck lymph nodes, and 60 Gy/30 fraction at 2.0 Gy/fraction to the PCTV1; 54 Gy/30 fractions at 1.8 Gy/fraction was given to the PCTV2. Among 59 patients with local advanced disease, 31 patients received concurrent chemoradiotherapy (chemo-RT) with a regimen consisting of 135 mg/m2 paclitaxel on Day 1 and 25 mg/m2 cisplatin on Days 1–3. The median follow-up period was 42 months. The local control rate (LCR), distant metastases-free survival (DMFS) and overall survival (OS) rates were 93.3%, 90.3% and 91.6% at 3 years, and 87.6%, 87.9% and 85.7% at 5 years, respectively. There was no significant difference in outcome with respect to these three indicators for Stage III and IV disease treated with/without concurrent chemoradiotherapy (P > 0.05). Acute toxicities included Grade 3 mucositis, skin desquamation, and leucopenia, which occurred in 78 (80.4%), 8 (8.2%), and 45 (46.4%) patients, respectively. No patient had a Grade 3–4 late toxicity. SMART was associated with a favorable outcome for NPC with acceptable toxicity. The local-regional control was excellent but distant metastasis remains the main risk. The combination of SMART and chemotherapy needs to be optimized through further studies to enhance outcomes for locally advanced diseases.

Simultaneous modulated accelerated radiation therapy for esophageal cancer: A feasibility study

To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN ±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.

EP-1156: Low esophageal toxicity during simultaneous modulated accelerated radiotherapy (SMART) in locally advanced NSCLC

EP-1156: Low esophageal toxicity during simultaneous modulated accelerated radiotherapy (SMART) in locally advanced NSCLC

RCMI et voies aérodigestives supérieures : le fractionnement différentiel a-t-il un intérêt ?

For head and neck cancer, intensity-modulated radiation therapy (IMRT) provides benefits in terms of coverage of the target tumour volume and reduction of the dose to organs at risk. Altered fractionation called SMART (simultaneous modulated accelerated radiation therapy) or SIB (simultaneous integrated boost), equivalent to the “concomitant boost” of conventional techniques, provides additional theoretical gain in the therapeutic index and simplifies the practical implementation of the treatment. The impact on tumour control and acute and late toxicities is encouraging but needs to be confirmed by prospective clinical studies with sufficient follow-up. A lot of different protocols have been tested without really bringing out a “gold standard”. However, the current results tend to suggest a SIB/SMART-IMRT moderately accelerated without combined chemotherapy for limited stages (I and II), and SIB-IMRT slightly accelerated with induction and/or concomitant chemotherapy for more advanced stages (III and IV).

Intensity-modulated radiotherapy with simultaneous modulated accelerated boost technique and chemotherapy in patients with nasopharyngeal carcinoma

BackgroundTo present our experience of intensity-modulated radiotherapy (IMRT) with simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC).MethodsSixty eight patients of NPC were treated between April 2006 and December 2011 including 45 males and 23 females with mean age of 46 (range 15–78). Stage distribution was; stage I 3, stage II 7, stage III 26 and stage IV 32. Among 45 (66.2%) evaluated patients for presence of Epstein-Barr virus (EBV), 40 (88.8%) were positive for EBV. Median radiation doses delivered to gross tumor volume (GTV) and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume (CTV) and 50.4 Gy to clinically negative neck. In addition 56 (82.4%) patients with bulky tumors (T4/N2+) received neoadjuvant chemotherapy 2–3 cycles (Cisplatin/Docetaxel or Cisplatin/Epirubicin or Cisplatin/5 Flourouracil). Concurrent chemotherapy with radiation was weekly Cisplatin 40 mg/m2 (40 patients) or Cisplatin 100 mg/m2 (28 patients).ResultsWith a median follow up of 20 months (range 3–43), one patient developed local recurrence, two experienced regional recurrences and distant failure was seen in 3 patients. Estimated 3 year disease free survival (DFS) was 94%. Three year DFS for patients with EBV was 100% as compared to 60% without EBV (p = 0.0009). Three year DFS for patients with undifferentiated histology was 98% as compared to 82% with other histologies (p = 0.02). Acute grade 3 toxicity was seen as 21 (30.9%) having G-III mucositis and 6 (8.8%) with G-III skin reactions. Late toxicity was minimal and loss of taste was seen in 3 patients (7.5%) at time of analysis.ConclusionsIMRT with SMART in combination with chemotherapy is feasible and effective in terms of both the clinical response and safety profile. EBV, histopathology and nodal involvement were found important prognostic factors for locoregional recurrence.

Phase I/II study of induction chemotherapy plus concurrent chemotherapy and SMART-IMRT-based radiotherapy in locoregionally-advanced nasopharyngeal cancer

This study aimed to evaluate the efficacy, toxicity and tolerability of simultaneous modulated accelerated radiation therapy (SMART)-intensity modulated radiotherapy (IMRT) plus cisplatin and 5-fluorouracil (5-FU) chemotherapy for patients with advanced nasopharyngeal cancer (NPC). Forty-five patients with stage II–IV NPC, determined by the American Joint Committee on Cancer system, were treated with prescribed doses of 72 Gy total to the gross tumor volume, 60 Gy to the clinical target volume and metastatic nodal station, and 54 Gy to the clinically-negative neck region. Before radiotherapy, two cycles of cisplatin (30 mg/m2/day on days 1–3) plus 5-FU (400 mg/m2/day on days 1–5) were delivered every three weeks for two cycles. Patients received two cycles of cisplatin (30 mg/m2 day on days 1–3) every three weeks during radiotherapy. In addition, two cycles of cisplatin and 5-FU were given after radiation. All patients completed the prescribed radiotherapy and all scheduled cycles of chemotherapy. Thirty of the 45 patients (66.6%) had a complete response at the end of treatment. Grade 3 mucositis occurred in 4/45 patients (8.8%) and grade 3 dermatitis occurred in 5/45 (11.1%) during radiotherapy. Grade 3 neutropenia occurred in 6/45 (13.3%) during concurrent chemotherapy. There was no treatment-related mortality. After a median follow-up time of 51 months, only three patients’ treatments had failed. Local and distant failure rates were 1.5 and 3.0%, respectively. SMART-IMRT plus cisplatin and 5-FU chemotherapy showed promising activity with manageable toxicity. It is a feasible regimen and improves locoregional disease control.

Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy

The aim of this phase 2 study was to determine the long-term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy. Eighty-one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m(2) /d on Days 1 and 22) was administered. The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow-up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5-year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5-year disease-free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow-up were grade 1-2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted. IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long-term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted.

Outcomes of Postoperative Simultaneous Modulated Accelerated Radiotherapy for Head-and-Neck Squamous Cell Carcinoma

To evaluate the treatment efficacy and toxicity of postoperative simultaneous modulated accelerated radiotherapy (SMART) for patients with head-and-neck squamous cell carcinoma (HNSCC). Between February 2003 and September 2008, 51 patients with histologically confirmed HNSCC received postoperative intensity-modulated radiotherapy (N=33) or helical tomotherapy (N=18) using SMART after curative surgical resection. The sites included were the oral cavity (OC), oropharynx (OP), larynx, and hypopharynx in 23, 20, 5, and 3 patients, respectively. The median follow-up duration of all patients and surviving patients were 32 (range, 5-78 months) and 39 months (range, 9-77 months), respectively. The 3-year overall survival, cause-specific survival, disease-free survival, locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) in all patients were 71%, 77%, 75%, 85%, and 82%, respectively. Although no significant difference in 3-year LRRFS were found between OC (82%) and OP (82%) carcinomas, the 3-year DMFS was worse in cases of OC (66%) carcinoma compared with OP carcinoma (95%; p=0.0414). Acute Grade 3 dermatitis, mucositis, and esophagitis occurred in 10%, 10%, and 2% of patients, respectively. At the last follow-up, Grade 3 xerostomia was documented in 10% of the patients. Young age (≤40 years) (p<0.001) and OC carcinoma primary (p=0.0142) were poor risk factors on univariate analysis for DMFS. Postoperative SMART was observed to be effective and safe in patients with HNSCC.