Introduction Of Intensity-modulated Radiotherapy Research Articles

Dosimetric Comparison of Unmatched Flattening Filter-free and Flattened Beams in Volumetric Arc Therapy Plans for Head-and-neck Cancer.

Conventionally, the fattened beam is being used in radiotherapy for routine clinical cases even after introduction of intensity-modulated radiotherapy with incorporation of multi-leaf collimator system. With the removal of the flattening filter (FF) from the beam's path average energy of the photon gets reduced resulting in reduced scatter, reduction in treatment time, and reduced neutron contamination for high-energy beam and ultimately resulting in treatment plan quality deviations. This study aims to investigate the usefulness of the FF-free (FFF) beam for routine head-and-neck cancer (HNC) cases treated with volumetric arc therapy (VMAT) and dosimetrically compares the result with the FF beam. In this study, 20 patients treated on HalcyonTM (unmatched 6 megavoltage [6MV] FFF beam) medical linear accelerator with VMAT of different HNC selected and for comparison with 6MV FF beam, 20 equivalent treatment plans are created for TruebeamTM configuration and the plans have been evaluated for target coverage, doses to the organ at risk (OAR), and other dose quality indices. Comparable target coverage, doses to OARs except for rest right parotid (P = 0.02) between 6MV FFF beam and 6MV FF beam is observed. Insignificant differences in conformity index, homogeneity index, and gradient index have been observed. Higher monitor unit (MU) (P ≤ 0.001) and lesser beam on time (BOT) (P = 0.003) have been observed in 6MV FFF. 6MV FFF beam provides comparable target coverage and improved dose-sparing effect to most of the OARs. 6MV FFF beam has lesser BOT, but on the other hand number of MUs is higher as compared to 6MV-FF plans.

Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer.

BackgroundLung cancer survival remains poor. The introduction of Intensity-Modulated Radiotherapy (IMRT) allows treatment of more complex tumours as it improves conformity around the tumour and greater normal tissue sparing. However, there is limited evidence assessing the clinical impact of IMRT. In this study, we evaluated whether the introduction of IMRT had an influence on the proportion of patients treated with curative-intent radiotherapy over time, and whether this had an effect on patient survival.Materials and MethodsPatients treated with thoracic radiotherapy at our institute between 2005 and 2020 were retrospectively identified and grouped into three time periods: A) 2005-2008 (pre-IMRT), B) 2009-2012 (selective use of IMRT), and C) 2013-2020 (full access to IMRT). Data on performance status (PS), stage, age, gross tumour volume (GTV), planning target volume (PTV) and survival were collected. The proportion of patients treated with a curative dose between these periods was compared. Multivariable survival models were fitted to evaluate the hazard for patients treated in each time period, adjusting for PS, stage, age and tumour volume.Results12,499 patients were included in the analysis (n=2675 (A), n=3127 (B), and n=6697 (C)). The proportion of patients treated with curative-intent radiotherapy increased between the 3 time periods, from 38.1% to 50.2% to 65.6% (p<0.001). When stage IV patients were excluded, this increased to 40.1% to 58.1% to 82.9% (p<0.001). This trend was seen across all PS and stages. The GTV size increased across the time periods and PTV size decreased. Patients treated with curative-intent during period C had a survival improvement compared to time period A when adjusting for clinical variables (HR=0.725 (0.632-0.831), p<0.001).ConclusionIMRT was associated with to more patients receiving curative-intent radiotherapy. In addition, it facilitated the treatment of larger tumours that historically would have been treated palliatively. Despite treating larger, more complex tumours with curative-intent, a survival benefit was seen for patients treated when full access to IMRT was available (2013-2020). This study highlights the impact of IMRT on thoracic oncology practice, accepting that improved survival may also be attributed to a number of other contributing factors, including improvements in staging, other technological radiotherapy advances and changes to systemic treatment.

Improved Tumor Control Related to Radiotherapy Technological Development for Hypopharyngeal Cancer.

Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P < .001) beginning in the 2000s. The 24-month FFLR using two-dimensional RT (2D-RT), three-dimensional conformal RT (3D-CRT), and intensity-modulated RT (IMRT) was 52%, 55%, and 80%, respectively; 24-month PFS was 39%, 46%, and 73%, respectively; and 24-month OS was 27%, 40%, and 68%, respectively. OS (P = .01), PFS (P = .03), and FFLR (P = 0.02) were improved with IMRT over 2D-RT, and FFLR appeared to be improved over 3D-CRT (P = .06). Controlling for chemotherapy use and other major variables, IMRT produced a strong influence over FFLR (adjusted hazard ratio [HR] = 0.2, 95% confidence interval [CI]: 0.0-1.2, P = .08) and a benefit in OS (adjusted HR = 0.1, 95% CI: 0.0-0.4, P = .005). Across 6 decades, patient and tumor characteristics remained similar whereas use of chemoradiation increased and IMRT was adopted. The introduction of IMRT was associated with improved FFLR, PFS, and OS, and a reduction in acute toxicity as compared to earlier radiation technologies. 4 Laryngoscope, 131:E452-E458, 2021.

New dose constraint reduces radiation-induced fatal pneumonitis in locally advanced non-small cell lung cancer patients treated with intensity-modulated radiotherapy

ABSTRACTBackground. Intensity-modulated radiotherapy (IMRT) in locally advanced non-small cell lung cancer (NSCLC) allows treatment of patients with large tumour volumes, but radiation pneumonitis (RP) remains a dose limiting complication. The incidence of severe RP using three-dimensional (3D) conformal radiotherapy, was previously reported to be 17%, with 2% lethal RP. The aim of this study was to monitor the incidence of RP following the introduction of IMRT.Material and methods. IMRT was delivered using 4–8 beam arrangements and introduced in three phases. In phase I, 12 patients were treated using only one dose constraint (V20), in which the total lung volume receiving 20 Gy was limited to 40%. In phase II, 25 patients were treated with an additional dose constraint of mean lung dose (MLD) ≤ 20 Gy. In phase III, 50 patients were treated with an extra dose constraint (V5) in which the total lung volume receiving a dose of 5 Gy was ≤ 60%. RP was prospectively documented. The results of phase I & II (IMRT-1) were compared to those in phase III (IMRT-2).Results. The median follow-up time was 17 months. The introduction of IMRT was associated with an increase in the incidence of RP in Phase I&II (IMRT-1) to 41%, six of 37 (16%) had grade 5 RP (IMRT-1). Introducing the dose constraint V5, led to a significant reduction in the lung volume receiving doses ≤ 20 Gy from 51 ± 2% to 41 ± 1% (p < 0.0001). Introducing V5 constraint did not decrease the incidence of severe (grade ≥ 3) RP, but significantly decreased the lethal pneumonitis to 4% (two of 50 patients), p = 0.05.Conclusion. Introducing IMRT resulted in an increase in the incidence of severe and fatal RP, however a new dose constraint to the volume of lung receiving low doses reduced the incidence of lethal pneumonitis.

Intensity-modulated radiotherapy vs. parotid-sparing 3D conformal radiotherapy

Intensity-modulated radiotherapy (IMRT) has rapidly become standard of care in the management of locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, our aim was to retrospectively investigate the effect of the introducing IMRT on outcome and treatment-related toxicity compared to parotid-sparing 3D conformal radiotherapy (3DCRT). A total of 245patients with stageIII and IV HNSCC treated with primary radiotherapy between January 2003 and December 2010 were included in this analysis: 135patients were treated with 3DCRT, 110patients with IMRT. Groups were compared for acute and late toxicity, locoregional control (LRC), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analysis and compared using a log-rank test. Acute toxicity was analyzed according to the Common Terminology Criteria for Adverse Events v3.0 and late toxicity was scored using the RTOG/EORTC late toxicity scoring system. Median follow-up was 35months in the IMRT group and 68months in the 3DCRT group. No significant differences were found in 3-year LRC and OS rates between the IMRT group and 3DCRT group. Significantly less acute mucositis ≥ grade3 was observed in the IMRT group (32% vs. 44%, p = 0.03). There was significantly less late xerostomia ≥ grade2 in the IMRT group than in the 3DCRT group (23% vs. 68%, p < 0.001). After 24months, there was less dysphagia ≥ grade2 in the IMRT group although differences failed to reach statistical significance. The introduction of IMRT in the radiotherapeutic management of locally advanced head and neck cancer significantly improved late toxicity without compromising tumor control compared to a parotid-sparing 3D conformal radiotherapy technique.

SU-E-T-390: Monitorization of the Dynamic Multi-Leaf Collimator Performance Using Log Files - a Quality Assurance Tool for Intensity Modulated Radiotherapy.

Commission baseline values of the multi-leaf collimator (MLC) using Varian's dynalog file viewer software (DFV) and establish tolerance levels to use as a periodic quality assurance tool in intensity modulated radiotherapy (IMRT). A sliding window test was created to have all leafs moving at a constant high speed of 2.5cm/s. This test was performed for 100 days at gantry angles of 0°, 90° and 270° during the morning quality checks in an accelerator performing RapidArc treatments with a Millennium 120 MLC. The DFV was used to collect the percentage of counts in bins 1 (0.05mm) to 8 (deviations in steps of 0.5mm) and the root mean square error (RMS). These were analyzed statistically and a baseline value and tolerance levels were established. Results show that the greater percentage of counts is found at bin 4 with an average of 97%. Bins 1 to 3 have less than 1 % and bin 5 presents an average of 1.7%. As for bin 6, the average was below 0.1%. Bins 7 and 8 presented no counts. When comparing the results of the different gantry angles, significant differences are only found in bin 4 and 5, with a better performance for the 0° gantry. As for the RMS error, no difference was found between different carriages or gantry angles and the average value was 0.129. A tolerance level was established for bins that correspond to greater deviations - bins 5 to 8, with an upper limit equivalent to twice the standard deviation of each bin. With the introduction of IMRT, the MLC quality assurance became more extensive and thorough. However a quantitative analysis is often difficult to interpret and time consuming. The purposed method allows the monitorization of the stability and performance of the MLC in a quantitative and easy way.

Concurrent radiochemotherapy in locally-regionally advanced oropharyngeal squamous cell carcinoma: analysis of treatment results and prognostic factors.

BackgroundConcurrent radiochemotherapy is a recommended treatment option for patients with locally advanced squamous cell head and neck carcinomas with recent data showing the most significant absolute overall and event-free survival benefit achieved in patients with oropharyngeal tumours. The aim of this study was to analyse the results of three-dimensional conformal radiotherapy given with concomitant weekly cisplatin in patients with advanced oropharyngeal carcinoma and to identify prognostic factors influencing outcomes of this patients category.MethodsSixty-five patients with stage III or IV squamous cell carcinoma of the oropharynx who underwent concurrent radiochemotherapy between January 2005 and December 2010 were retrospectively analyzed. All patients received radiotherapy to 70 Gy/35 fractions/2 Gy per fraction/5 fractions per week. Concurrent chemotherapy consisted of weekly cisplatin (30 mg/m2) started at the first day of radiotherapy.ResultsMedian age was 57 years (range, 36 to 69 years) and 59 (90.8%) patients were male. Complete composite response was achieved in 47 patients (72.3%). Local and/or regional recurrence was the most frequent treatment failure present in 19 out of 25 patients (76.0%). At a median follow-up of 14 months (range, 5 to 72 months), 2-year local relapse-free, regional relapse-free, locoregional relapse-free, disease-free, and overall survival rates were 48.8%, 57.8%, 41.7%, 33.2% and 49.7%, respectively.On multivariate analysis the only significant factor for inferior regional relapse-free survival was the advanced N stage (p = 0.048). Higher overall stage was independent prognostic factor for poorer local relapse-free survival, locoregional relapse-free survival and disease-free survival (p = 0.022, p = 0.003 and p = 0.003, respectively). Pre-treatment haemoglobin concentration was an independent prognostic factor for local relapse-free survival, regional relapse-free survival, locoregional relapse-free survival, disease-free survival, and overall survival (p = 0.002, p = 0.021, p = 0.001, p = 0.002 and p = 0.002, respectively).ConclusionsPoor treatments results of this study suggested that introduction of intensity-modulated radiotherapy, use of induction chemotherapy followed by concurrent radiochemotherapy, accelerated radiotherapy regimens, and molecular targeted therapies could positively influence treatment outcomes. The incorporation of reversal of anaemia should be also expected to provide further improvement in locoregional control and survival in patients with advanced squamous cell carcinoma of the oropharynx.

Combined-modality treatment improved outcome in sinonasal undifferentiated carcinoma: single-institutional experience of 21 patients and review of the literature

The optimal treatment of sinonasal undifferentiated carcinoma (SNUC) remains unclear. We report our results on the outcome and toxicity of patients with SNUC treated by a combined modality and attempt to define the optimal treatment strategies by reviewing the literature. Between 1996 and 2010, 21 consecutive patients with SNUC were treated by any combination of surgery, chemotherapy and radiotherapy. End points were local control (LC), regional control (RC), disease-free (DFS), cause-specific (CSS) overall survival (OS), and late toxicity. Organ preservation was defined as visual preservation without orbital exenteration. After median follow-up of 54 months, the 5-year actuarial rates of LC, RC, DFS, CSS, and OS were 80, 90, 64, 74, and 74 % respectively. On multivariate analysis, T-stage and multimodality treatment approach correlated significantly with LC. Elective nodal irradiation was given to 42 % of high-risk node-negative patients. None of them developed regional failure. The overall 5-year incidence of grade ≥2 late toxicity was 30 %. Treatment-related blindness was significantly decreased in patients treated with intensity-modulated radiotherapy (IMRT), compared to 2D and 3D-conformal radiotherapy (3DCRT), with organ preservation rates of 86 and 14 % respectively (p = 0.006). We concluded that combined-modality treatment with three, or at least two, modalities resulted in good LC, but with high overall rate of late toxicity. However, the incidence of late toxicity and permanent visual impairment were decreased over time by the introduction of IMRT. Because of the improvement in therapeutic ratio achieved by using IMRT, this highly conformal radiation technique should be the standard of care in patients with SNUC.

Post-treatment late complications of nasopharyngeal carcinoma

Radiotherapy (RT) or concurrent chemoradiation therapy (CCRT) is not only effective at patients' survival rates, but also produces undesirable late complications. The purpose of this study is to investigate the post-treatment late complications in nasopharyngeal carcinoma (NPC) patients, and to analyze the individual impact factors. We enrolled 188 newly diagnosed NPC patients who had received complete treatments and at least 3years' follow-up between March 1984 and March 2010. Late complications were modified from the Toxicity Criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer. Of 188 patients, 132 were male and 56 were female. Eighty-eight patients received CCRT and the other 100 patients received RT alone. The median follow-up duration was 7.34years (range 3.30-26.54). Only 5.3% of patients reported no complication during post-treatment follow-up. The most common major and minor complications were osteoradionecrosis (10.1%) and xerostomia (56.4%), respectively. There was no impact factor for age, underlying disease, and cancer staging. However, there was a negative impact factor for xerostomia and limb numbness in the CCRT group compared with the RT group. Besides, re-radiation for recurrent patients could increase the risk of major complications. Fortunately, these major complications were reduced after the introduction of intensity-modulated radiotherapy in 2003. The improvement of treatment modality decreased the risk of major complications. Physicians should pay more attentions and improve patients' quality of life during follow-up.

Early mesothelioma revisited

Very recently, a randomized controlled trial successfully proved a significant reduction in lung cancer mortality with CT screening [1]. This was an epoch-making report. Although intuition had been telling us that early detection of lung cancer converts directly into reduced mortality, most previous studies have only proven an improved detection rate; they have failed to show any reduction of mortality from lung cancer [2–4]. The success of the present study was obtained by focusing on a high-risk population. Although primary lung cancer had been—as MPM still is—considered a highly incurable disease, its mortality is currently much improved. For example, in the Japanese Lung Cancer Registry, the 5-year survival rate for all surgical cases was 51.9% in 1996 and 69.6% in 2004 [5]. This striking improvement in survival may be multifactorial, but early diagnosis and early treatment are undoubtedly the most important factors. In this registry, 48.1% of the 11663 surgical cases in 2004 were at pathological stage Ia, and the 5-year survival rate of this subgroup reached 85.1% [5]. On the other hand, MPM remains one of the most incurable malignancies, and its median survival time (MST) after diagnosis is approximately 1 year [6–8]. Therapy for MPM (just like other malignancies) has evolved considerably, and is still evolving: adjuvant chemotherapy [9], neoadjuvant chemotherapy [10], the introduction of pemetrexed [11–13], the reduction in mortality/ morbidity after extrapleural pneumonectomy (EPP) [14, 15], the introduction of radical pleurectomy/decortication (P/D) [16–19], adjuvant radiotherapy [20, 21], the introduction of intensity-modulated radiotherapy (IMRT) [22–25], and so on. Trimodality treatment (TMT) with induction chemotherapy followed by extrapleural pneumonectomy (EPP) and postoperative radiation was introduced as an integration of the above developments, and is currently considered the most powerful therapeutic option [10, 26–32]. TMT is only feasible for highly selected patients with early MPM and excellent cardiopulmonary reserve. However, notwithstanding its high cost, its extremely high risk, and its severe deterioration of cardiopulmonary function, MST after TMT still does not reach 20 months in most large studies [29–31, 33], so some researchers are skeptical about aggressive surgery in MPM patients [33, 34]. In the above context, the current therapeutic options are not sufficient to provide acceptable survival in cases with non-early MPM.

Reducing xerostomia through advanced technology

Radiation-related xerostomia has been the most significant and disabling side-effect of radiotherapy for head and neck cancer for more than 50 years. With the PARSPORT trial, reported in The Lancet Oncology,1 the largest and best designed of several randomised trials focusing on xerostomia, radiation oncologists and their partners in physics and dosimetry should take pride that significant progress has been made. Before the introduction of intensity-modulated radiotherapy (IMRT), more than 80% of survivors experienced substantial dry mouth syndrome and associated effects on dental health, swallowing, taste, and quality of life.

Quantification of tumour hypoxia

Tumor cell hypoxia is considered one of the important causes for radiation resistance. The introduction of IMRT(intensity modulated radiotherapy) allows specific boosting of tumor subvolumes that may harbour these radioresistant tumour cells. PET imaging of these subvolumes can be incorporated into treatment planning. However, at this moment microenvironmental changes visualized and quantified by means of PET-imaging need to be validated by high-resolution microscopic techniques. This will allow interpretation of imaging techniques with intermediate resolution (such as PET/CT) in relation to complex cellular signaling in response to anti-cancer treatments.

Research Highlights

Research Highlights

Are We Influencing Outcome in Oropharynx Cancer With Intensity-Modulated Radiotherapy? An Inter-Era Comparison

To analyze the outcome in all oropharynx cancer patients treated at the University of Wisconsin during 1995-2005 and highlight the methodologic challenge in comparing outcome after intensity-modulated radiotherapy (IMRT) with that of historical controls. Outcomes were compared in 195 oropharynx cancer patients after definitive radiotherapy with curative intent in the pre-IMRT era (pre-IMRT, n = 105), after IMRT (IMRT+, n = 52) or after non-IMRT techniques during the IMRT era (IMRT-, n = 38). With a median follow-up of 30.4 months, the 3-year overall survival rate in IMRT+, IMRT-, and pre-IMRT patients was 88.2%, 81.1%, and 67.7%, respectively; and for locoregional control was 96.1%, 78.1%, and 81.1%. Patients from the IMRT era more frequently received concurrent chemotherapy (67% vs. 6%, p < 0.001) and underwent adjuvant neck dissection (52% vs. 29%, p = 0.002). Patients with T3-4 disease and bilateral neck disease were significantly less likely to receive IMRT. Cox regression analysis identified IMRT as a significant prognostic factor (p = 0.04); however, after including T stage in the model, IMRT lost independent significance (p = 0.2). Analysis of a potential effect of IMRT on Grade 3+ mucositis or skin reaction was also hampered by the change in other treatment characteristics. Outcomes in oropharynx cancer have improved at our institution since the introduction of IMRT. However, multiple factors have contributed to this improvement, and presentation of IMRT outcomes without the full context of historical and contemporary controls may yield data that overstate outcome after IMRT.

Clinical implementation of dynamic intensity-modulated radiotherapy: radiographers' perspectives.

The ability of intensity-modulated radiotherapy (IMRT) to sculpt the dose distribution closely around the tumour volume has the potential to have a major impact on radiotherapy clinical practice. However, dynamic IMRT treatment delivery differs from that of conventional treatment because of the constantly moving multileaf collimators (MLCs) and higher monitor units (MUs) required. The implementation of new technology can be affected by the users response. Radiographers' attitudes regarding technology and their perceptions of the clinical implementation of IMRT were explored using a qualitative study based on semi-structured interviews. 16 radiographers were interviewed and data was analysed using a framework analysis to identify themes and categories. The majority of radiographers (12/16) demonstrated positive attitudes regarding technology. The introduction of IMRT was seen to be stimulating and motivating. Negative aspects were associated with increased stress from learning new skills and the additional pressure of the increased workload. Although there were contradictory views regarding the effect of the increased use of technology on the patient-radiographer relationship, technological skills and patient care were not found to be mutually exclusive. Radiographers' perceptions regarding the clinical implementation of IMRT appeared to be influenced by their mainly positive attitudes regarding technology. With the current problems of recruitment and retention of radiographers, full exploitation of modern technology could be used to improve job satisfaction. However, careful integration is required to balance training needs with service demands.