Intensity-modulated Radiotherapy Arm Research Articles

Impact of Radiation on Dysphagia-Related Structures: A Dosimetric and Clinical Comparative Analysis of Three-Dimensional Conformal Radiotherapy (3D-CRT) and Intensity-Modulated Radiation Therapy (IMRT) Techniques in Patients With Head and Neck Cancer.

Introduction Head and neck squamous cell carcinoma (HNSCC)is a significant health concern in India, with around one million new cases annually. The prevalence of HNSCC is notably high in Asia, especially in India, due to habitslike tobacco chewing, betel nut usage, and alcohol consumption. Treatment typically involves a combination of surgery, radiation, chemotherapy, and biological therapy, aiming for tumor control while preserving function and quality of life. However, survivors often face long-term side effectslike difficulty swallowing, leading to complicationssuch as aspiration pneumonia. Intensity-modulated radiotherapy (IMRT) has shown promise in improving outcomes by sparing critical swallowing structures. Efforts to minimize radiation-related dysphagia are crucial for enhancing patients' quality of life post-treatment. Our study focuses on examining dosimetric parameters associated with dysphagia aspiration, alongside evaluating dysphagia grades in both treatment groups using the RTOGscale. Material and methods Patients with histologically confirmed non-metastatic head and neck carcinomas were included in our study in November 2018-April 2020. A total of 56 patients were taken into our study with 28 in each arm. They underwent radical radiotherapy (RT) with a total dose of 66-70 Gy, with or without concurrent chemotherapy, meeting specific inclusion criteria and excluding those receiving reirradiation or with distant metastasis. Patients were divided into two groups: Group I received three-dimensional conformal radiotherapy (3D-CRT), and Group II received IMRT. Treatment planning involved immobilization, CT imaging, delineation of target volumes and organs at risk, and contouring of swallowing structures. Dose-volume histogram parameters (mean dose, maximum dose, V30, V70, V80, D50, and D80) were used to assess mean dose to swallowing structures outside the planning target volume (PTV), with a mean dose constraint of 50 Gy. Dysphagia was evaluated using the RTOGcriteria at baseline, during treatment, and six months post-treatment. Statistical analysis was performed using SPSS, with significance set at p < 0.05. Results In our study, the mean age at presentation differed slightly between the IMRT and 3D-CRT arms: 58 years versus 55 years, respectively. A higher proportion of patients in both arms experienced symptoms for three to six months, with 53.6% in 3D-CRT and 42.9% in IMRT. Stage distribution varied, with IV being most common in 3D-CRT and stage II in IMRT. Approximately 56% of patients in both groups had a history of smoking. Significant differences were observed in spinal cord dose between 3DCRT and IMRT techniques (p < 0.001). Similarly, a significant difference was found in the mean dose received by dysphagia aspiration-related structures (DARSs) between the 3D-CRT and IMRT arms (p = 0.04). Patients in the IMRT arm exhibited superior dysphagia grades compared to those in the 3D-CRT arm, with statistical significance observed in the third month (p = 0.008) and sixth month (p = 0.048). Conclusion Our study found a notable decrease in the mean DARS dose and reduced dysphagia severity at three and six months in the IMRT group compared to the 3D-CRT group. However, due to the diverse study population, establishing a definitive correlation between the DARS dose and dysphagia severity was challenging. Future large-scale studies are needed to validate these findings for improved preservation of DARS structures.

Comparison of Acute Gastrointestinal Toxicity of Intensity-Modulated Radiotherapy Versus Three-Dimensional Conformal Radiotherapy in Patients of Carcinoma Cervix.

Introduction Cervical cancer is the most common gynaecological malignancy worldwide, with a higher prevalence in middle- and low-income countries. Chemoradiotherapy, followed by intracavitary brachytherapy, is the treatment of choice in locally advanced cervical cancer. The most common acute side effect of external beam radiotherapy (EBRT) is bowel toxicity in the form of diarrhoea and abdominal cramps. The treatment techniques of EBRT were revolutionised with the advent of intensity modulation. This study aims to prospectively analyse whether the dosimetric advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3DCRT) is translated clinically into a decrease in acute toxicity. Method Twenty-four patients were randomised into two groups: the 3DCRT and the IMRT. Acute gastrointestinal (GI) toxicity was assessed during treatment using radiation therapy oncology group grading. The factors under consideration were age, stage of the disease, treatment technique, chemotherapy, and the intention of therapy (radical or adjuvant). The mean bowel bag dose of the two techniques was analysed. Result Among the factors under consideration, it was found that the treatment technique was the only factor that had a significant association with acute bowel toxicity in both univariate (p = 0.036) and multivariate analyses (p = 0.028). The mean V25 (the volume receiving 25 Gy), V45, and V50 of the bowel bag in the IMRT arm were significantly less than the 3DCRT arm. Grades 2 and 3 acute bowel toxicities were also higher in the 3DCRT arm. Conclusion The treatment technique is essential to determining acute GI toxicity during pelvic radiotherapy. With IMRT, the dose to the bowel bag and, in turn, the acute bowel toxicity can be reduced.

Intensity-Modulated Radiation Therapy Alone Versus Intensity-Modulated Radiation Therapy and Brachytherapy for Early-Stage Oropharyngeal Cancers: Results From a Randomized Controlled Trial

The objective of this study was to compare clinical outcomes of intensity-modulated radiation therapy (IMRT) alone versus IMRT + brachytherapy (BT) in patients with T1-T2N0M0 oropharyngeal squamous cell cancers (OPSCC). This open-label randomized controlled trial was conducted at Tata Memorial Hospital, Mumbai, India. Patients with stage I and II OPSCC were considered for IMRT to a dose of 50 Gy/25 fractions/5 weeks in phase I followed by randomization (1:1) to further treatment with IMRT (20 Gy/10 fractions/2 weeks) or BT (192Ir high dose rate, 21 Gy/7 fractions/2 fractions per day). The primary endpoint of the trial was the reduction in xerostomia at 6 months evaluated using 99mTc salivary scintigraphy. Severe salivary toxicity (xerostomia) was defined as posttreatment salivary excretion fraction ratio <45%. Secondary endpoints were local control, disease-free survival, and overall survival. Between November 2010 and February 2020, 90 patients were randomized to IMRT (n = 46) alone or IMRT + BT (n = 44). Eleven patients (8 residual/recurrent disease, 2 lost to follow-up, 1 second primary) in the IMRT arm and 9 patients (8 residual/recurrence, 1 lost to follow-up) in the BT arm were not evaluable at 6 months for the primary endpoint. At 6 months, xerostomia rates using salivary scintigraphy were 14% (5/35: 95% CI, 5%-30%) in the BT arm while it was seen in 44% (14/32: 95% CI, 26%-62%) in the IMRT arm (P = .008). Physician-rated Radiation Therapy Oncology Group grade ≥2 xerostomia at any time point was observed in 30% of patients (9/30) in the IMRT arm and 6.7% (2/30) in the BT arm (P = .02). At a median follow-up of 42.5 months, the 3-year local control in the IMRT arm was 56.4% (95% CI, 43%-73%) while it was 66.2% (95% CI, 53%-82%) in the BT arm (P = .24). The addition of BT to IMRT for T1-T2N0M0 OPSCC results in a significant reduction in xerostomia. This strongly supports the addition of BT to IMRT in suitable cases.

Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer

Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022. The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning). The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival. A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms. This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates. ClinicalTrials.gov Identifier: NCT01874587.

A Prospective Cohort Study Analyzing Radiation-Induced Xerostomia and Quality of Life of Head and Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy Techniques at a Tertiary Cancer Center in Eastern India.

Introduction Cancer of the head and neck is one of the most common cancers in India. Radiotherapy (RT) plays a vital role in the management of head and neck cancer both as a curative and adjuvant modality. Xerostomia is the most common acute and late toxicity. Therefore, this study aimed to analyzeradiation-induced xerostomia and the quality of life of patients treated with intensity-modulated radiotherapy (IMRT) and three-dimensional (3D) conformal radiotherapy (3DCRT). Objectives We aimto evaluate radiation-induced acute xerostomia both subjectively and objectively at three-monthand one-year post-radiotherapy follow-up period in patients who received radiotherapy in conformal technique (IMRT) to the head and neck region and compare it with those who received the 3DCRT technique. We also aim to assess the recovery of salivary flowin the third month post-radiotherapy by measuring the parotid scintigraphy excretion fraction. Materials and methods Forty patients with head and neck squamous cell carcinoma (SCC) were randomly assigned to the IMRT and 3DCRT arms. Xerostomia during radiation and at three-monthand one-year post-radiotherapy follow-up was assessed subjectively using the xerostomia-related quality of life (XeQOL)questionnaire and objectively by measuring the salivary flow rate and parotid scintigraphy. Results The result is analyzed using an independent t-test, Mann-Whitney U test, and Fisher's exact test. The analysis showed that patients treated with radiation by IMRT showed better XeQOL scores (43.40±2.326 in IMRT and 52.10±2.573 in 3DCRT, p<0.001) and Eating Assessment Tool-10 (EAT-10) score (27.65±2.796 in IMRT and 33.80±1.936 in 3DCRT, p<0.001) compared to those treated with 3DCRT. Analysis of the excretion fraction (EF%) of parotid scintigraphy depicted improvement in EF% for both right and left parotids in the IMRT arm with statisticalsignificance (for right parotid, 25.22±12.98 in IMRT and 19.60±10.17 in 3DCRT, p=0.136, and for left parotid, 28.03±12.51 in IMRT and 15.35±11.49 in 3DCRT, p=0.0019). The mean rate of flow (ROF) of saliva showed a declining trend during the end of radiotherapy treatment compared to baseline, but the mean ROF of saliva was better in IMRT compared to 3DCRT, and the difference was statistically significant. The ROF of saliva starts improving during the one-year post-radiotherapy follow-up period. Pearson's chi-square test was used to analyzethe correlation between mean parotid dose with EF% of parotid scintigraphy,and it showed a negative correlation, which is statistically significant for both 3DCRT and IMRT arms. Conclusion Xerostomia can be reduced by precision radiotherapies such as the parotid-sparing IMRT technique in head and neck cancer patients, hence improving the quality of life.

Angle of concavity in planning target volume can be adopted as selection criteria for intensity-modulated radiation therapy or three-dimensional conformal radiotherapy technique in brain tumors.

With innovation of medical imaging, radiotherapy attempts to conform the high dose region to the planning target volume (PTV). The present work aimed to assess the angle of concavity in PTV can be adopted as selection criteria for intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT) technique in Brain tumors. Thirty previously irradiated patients with brain tumors were replanned with both 3DCRT and IMRT technique. Angle of concavity (dip) in the PTV near the organs at risk was measured in the contoured structure set images of each patient. These cases were divided into three groups where angles were 0°, >120° and <120°. Dose of 60 Gy/30# was fixed. In Group 1, the IMRT plan had better TV95% as compared to 3DCRT respectively with significant P value (P = 0.002). Mean of conformity index (CI) and Homogeneity Index (HI) were comparable. For Group 2 (angle >120°), the IMRT plan had better TV95% as compared to 3DCRT respectively with a significant P value (P = 0.021). HI and CI were not significant. For Group 3 (<120°), IMRT plan had better TV95% as compared to 3DCRT respectively with a significant P value (P = 0.001). HI and CI were better in IMRT arm with significant P value. The results from this study showed that the angle of concavity can be considered as an additional objective tool for selection criteria whether tumor can be treated with IMRT or 3DCRT. Tumors where angle of concavity was <120°, HI and CI provided more uniformity and conformity of dose distribution inside PTV with significant P values.

Quality of Life Analysis of a Phase II Randomized Controlled Trial Comparing 3D-Conformal Radiotherapy (3D-CRT) and Intensity Modulated Radiotherapy (IMRT) in Locally Advanced Rectal Cancer (TRI-LARC)

<h3>Purpose/Objective(s)</h3> The aim of the study was to compare the use of 3D-CRT and IMRT in pre-operative long course chemo-radiotherapy for locally advanced rectal cancer. We herein evaluate the impact of the two treatment modalities on quality of life (QOL), a secondary objective of the study. <h3>Materials/Methods</h3> 94 patients with rectal adenocarcinoma were enrolled in a prospective randomized phase II trial across three institutions between 2014 and 2020. Eligible patients had stage T3-4, N(any) or circumferential resection margin at risk with no evidence of metastatic disease. All patients were prescribed 50.4Gy in 28 fractions with concomitant 5-fluorouracil or capecitabine. Patients were randomly assigned (1:1) to 3D-CRT and IMRT planning techniques. QOL was assessed using the EORTC QLQ C30 and QLQ CR29 questionnaires at baseline, during the final week of radiotherapy and at six and twelve months after radiotherapy. A paired sample t test was used to compare differences in QOL from baseline to each follow-up. One-way between-group analyses of covariance (ANCOVA) were conducted to compare the effect of the trial arms on each QOL score. <h3>Results</h3> At a median follow-up of 14 months, the trial was terminated early due to failure to establish efficacy in the primary outcome, acute gastrointestinal toxicity. The median age was 59 years and 72/94 (77%) were male. 86/94 (91%) patients completed the baseline and at least one other QOL assessments. QOL data at one year was available in 55/94(58%). At baseline, there was no difference in QOL scores between trial arms. Overall, emotional functioning had improved at six months but physical, cognitive, role and social functioning had declined. At six months, there was a significant improvement in constipation, blood and mucous in stool, bloating, urinary frequency, buttock pain and anxiety scores compared to baseline. There was a significant deterioration in dyspnea, fatigue, nausea/vomiting, taste, hair loss, erectile dysfunction, body image and global health scores from baseline to 6-month follow-up. After adjusting for pre-intervention score, the IMRT arm had better physical functioning (p=0.038) and role functioning (p=0.014) during the final week of radiotherapy compared to the 3DCRT arm. The end of radiotherapy embarrassment score, for those without a stoma, was significantly worse in the IMRT arm (p=0.032). There was no other significant difference in QOL scores between the two arms, at either the final week of radiotherapy or at 6 months, after adjustment for pre-intervention scores. The limitations of the study include its early termination, the potential for type 1 error and the possible influence of other factors on QOL data such as chemotherapy and postoperative complications. <h3>Conclusion</h3> There are limited QOL benefits of IMRT compared to 3D-CRT in the neoadjuvant setting for rectal cancer.

Acute Gastrointestinal Toxicity Results from a Multi-Institution, Phase 2, Randomized Controlled Trial Comparing 3D-Conformal Radiotherapy (3DCRT) Versus Intensity Modulated Radiotherapy (IMRT) for Locally-Advanced Rectal Cancer (TRI-LARC).

<h3>Purpose/Objective(s)</h3> The primary aim of this trial was to compare the incidence of grade 2 or above acute gastrointestinal (GI) toxicity for patients undergoing 3DCRT versus IMRT in the preoperative setting for locally-advanced rectal cancer. Secondary objectives included quality of life and other acute and late toxicity. <h3>Materials/Methods</h3> The trial was designed to have 80% power to detect a difference between a hypothesized 37% acute toxicity rate in the 3DCRT arm (Bosset et al, 2006) and 20% in the IMRT arm, with a sample size of 120 per arm, and a 0.05 two-sided level of significance. Eligible participants were adults aged 18 or over scheduled to receive pre-operative pelvic chemo-radiotherapy for histologically-confirmed rectal adenocarcinoma. Exclusion criteria included prior pelvic radiotherapy, inflammatory bowel disease, hip replacements, and previous bowel surgery. Prescription dose was 50.4 Gray in 28 fractions over 5.5 weeks with concurrent 5-fluorouracil or capecitabine chemotherapy. Participants were centrally randomized 1:1 to receive 3DCRT or IMRT. Each individual radiotherapy volume and plan was reviewed centrally to ensure compliance with the trial's RTQA specifications. Toxicity was graded and reported according to CTCAE version 4.0 (National Institutes of Health National Cancer Institute). Acute toxicity was assessed weekly during radiotherapy, and at 2- and 4-weeks post-treatment. <h3>Results</h3> 94 patients were enrolled. 77% were male and median age was 59.4. Two participants from the 3DCRT arm did not complete radiotherapy as planned and were excluded from analysis. 25 (56%) of participants from the 3dCRT arm and 23 (49%) from the IMRT arm experienced acute grade 2 or above GI toxicity (p=.670). Rates for grade 3 GI toxicity were 8 (18%) and 5 (11%) for 3dCRT and IMRT, respectively (p=.494). Grade 3 GI events included diarrhea (n=11), nausea (n=2), intestinal obstruction (n=1), oral mucositis (n=1), and rectal pain (n=1). The study closed early due to absence of evidence of a difference between arms at the interim analysis. <h3>Conclusion</h3> No significant difference in rates of acute GI toxicity with IMRT versus 3DCRT for locally advanced rectal cancer was seen. Although IMRT can reduce dose to organs at risk, it appears to be similarly safe in terms of acute GI toxicity to deliver this treatment with 3DCRT.

Months and Severity Score (MOSES) in a Phase III trial (PARCER): A new comprehensive method for reporting adverse events in oncology clinical trials

SummaryBackgroundAdverse event reporting in oncology trials lacks temporal description. We propose a toxicity summarizing method that incorporates time.MethodsPatients recruited in a phase III trial (NCT01279135) that compared three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for late toxicity in cervical cancer were included. Adverse events were reported using Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and quality of life (QOL) with EORTC QLQ-C30 and CX24. A total of six symptoms with a related QOL question (diarrhoea, abdominal pain, anorexia, urinary incontinence, frequency and fatigue) were included. Month and severity score [MOSES= ∑ (CTCAE grade x proportionate time)] was calculated. Cumulative-MOSES (C-MOSES) was calculated by summating these 6 individual MOSES. QoL was categorized as "substantially symptomatic" or “not”. Receiver operator curve analysis was performed to determine the MOSES cut off that predicts for substantial QOL symptoms. CTCAE and MOSES were tested for accurately categorizing QOL impact.FindingsIn the construction dataset, 201/300 patients had symptoms. MOSES > 0.20 had higher accuracy than CTCAE for predicting impact on QOL related to diarrhoea (85% vs. 69%), anorexia (61% vs 51%), abdominal pain (71% vs. 57%), urinary incontinence (72% vs. 61%) and frequency (62% vs. 59%). C-MOSES > 0·70 correlated with reduction in role functioning and global QOL. While no difference was seen in CTCAE grade ≥1 Gastrointestinal (GI) toxicity between 3DCRT or IMRT arm, 3DCRT had higher C-MOSES than IMRT (HR=0.64;95% CI 0.41–0.99, p = 0.04).InterpretationMOSES has higher accuracy than CTCAE in categorizing symptom specific and functional QOL. These results require further external validation.FundingNone.

Delineation of Oral Mucosa as a Pseudo-Organ-at-Risk May Lead to a Decrease in the Incidence of Oral Mucositis: A Dosimetric Analysis of Intensity-Modulated Radiation Therapy Plans in Head and Neck Cancers.

IntroductionOral mucositis is a common and potentially serious complication of radiation in head and neck cancer treatment. Severe mucositis causes pain, difficulty in chewing and swallowing that can cause treatment breaks and can cause treatment failures leading to local recurrence or a decrease in overall survival. The contouring of the planning target volume (PTV) and organ at risk (OAR) leaves some undefined regions on computed tomography imaging. The treatment planning system uses these regions as dumping sites for the dose in order to achieve the optimum plan. The present study was done to assess the dose going to these unspecified regions termed as pseudo-OARs and whether delineation of these structures and prescribing a dose constraint will reduce the dose to the oral mucosa without compromising the quality of the treatment plan.MethodsTwenty patients of head and neck cancer were selected and were randomly placed in two arms. One was intensity-modulated radiation therapy (IMRT) arm I, which included the initial plans with which the patients were treated where the pseudo-OAR was not delineated and hence was not considered in the planning process. After giving treatment, the pseudo-OAR was delineated to see the dose dumped into the area outside the PTV. The other was IMRT arm II, where another virtual plan of the same patients of arm I was made wherein the delineation of the pseudo-OAR was done before planning and dose constraint prescribed. The pseudo-OAR consisted of anterior oral mucosa, part of mandible and maxilla, which was adjacent to the PTV in oropharynx and contralateral buccal mucosa patients. The dose constraint given to the pseudo-OAR was Dmean ≤30 Gy. Statistical significance was calculated by using a paired t-test. A p-value of <0.05 was considered as statistically significant.ResultsThe dosimetric parameters of PTV were comparable in both the IMRT arms. The pre-specified objective was fulfilled with both the study arms. The dose homogeneity and conformity was also similar. The dosimetric parameters of other OARs were within the prescribed dose constraints. The Dmean value of the pseudo-OAR in arm I was 31.28 Gy ± 3.55 Gy and 7.87 Gy ± 9.11 Gy in arm II and the p-value was significant (p=0.001), whereas the Dmax in arm I was 61.82 Gy ± 5.91 Gy and 61.23 Gy ± 5.54 Gy in arm II (p=0.6). The dose to the pseudo-OAR in IMRT arm II was reduced drastically by 75%, which was statistically significant.ConclusionThe delineation of oral mucosa as a pseudo-OAR should routinely be done. The dose constraints need to be optimized by clinical studies, which might probably decrease the incidence and severity of oral mucositis.

A Prospective Randomized Study of Intensity-Modulated Radiation Therapy Versus Three-Dimensional Conformal Radiation Therapy With Concurrent Chemotherapy in Locally Advanced Carcinoma Cervix.

Background: External Beam Radiotherapy is the treatment of choice of locally advanced carcinoma cervix (LACC). The two techniques, three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT), have been compared previously in terms of outcomes and toxicities. IMRT has still not shown any benefit over 3DCRT in terms of local control and survival. Hence, the present study was conducted to compare local control and toxicities among both techniques.Material & Methods: Fifty-four patients of LACC (FIGO IB2-IVA) were randomized to receive 50 Gray in 25 fractions by either 3DCRT or IMRT with concurrent cisplatin-based chemotherapy followed by brachytherapy. Plans were compared for planning target volume (PTV) coverage, dose to organs at risk (OAR), homogeneity index (HI), and conformity index (CI). Patients were assessed for acute toxicity and local control for three months.Results: Out of 54 patients, 27 received treatment by 3DCRT and 27 by IMRT technique. Dosimetric evaluation for PTV coverage was similar in both arms. D15, D35, and D50 (dose to 15%, 35%, and 50% volume, respectively) for bladder were significantly reduced in the IMRT arm. Dosimetry for rectum and bowel bag was similar in both. There was a significantly decreased dose to femoral heads in the IMRT arm. Patients in the 3DCRT arm had significant grade 1 and 2 anemia and neutropenia compared to the IMRT arm. Local control for three months was similar in both the arms.Conclusion: IMRT is associated with decreased acute hematological toxicity compared to 3DCRT with similar local control. Long-term follow-up is needed to assess any difference in long-term toxicity and survival between the two arms.

Qualitative and dosimetric assessment of radiation-induced xerostomia in patients with oral cancers treated with 3DCRT versus IMRT: A prospective observational study

Background: Xerostomia is an important complication in patients with head-and-neck cancer treated with radiotherapy. It is caused by the radiation dose to the salivary glands situated in the lateral facial and submandibular regions, which are commonly included in or are close to the target volume.Objectives: Our primary objective was to evaluate xerostomia in patients treated with three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT). We also aimed to identify the risk factors for the development of xerostomia and the treatment-related and dosimetric parameters associated with xerostomia in patients with oral cancers receiving radiotherapy.Materials and Methods: We enrolled 100 patients with oral cancers between Sept 2015 and Apr 2018 who were planned for adjuvant radiotherapy. Patients were treated with unilateral portals in 3DCRT or IMRT. Xerostomia was assessed using the Wake Forest National Cancer Institute Community Oncology Research Program Research Base (WF NCORP RB) # 97115 Questionnaire at baseline, treatment completion, and at 1, 4, and 7 months following the completion of radiotherapy. Detailed salivary gland dosimetric parameters including the minimum (Dmin), maximum (Dmax), and mean dose (Dmean) and other dose and volume parameters (e.g., D25, D50, D75, and V10–V60) were assessed through cumulative dose volume histograms (DVH). Multivariate analysis was performed to determine the factors associated with the development of xerostomia and assess the correlation with dosimetric parameters.Results: At a median follow-up of 20 (95% confidence interval [CI], 8–32) months, the V20, V25, V30, V40, V45, V50, V60, Dmin, and Dmean received by the ipsilateral parotid gland were significantly lower in patients treated with IMRT compared to those treated with 3DCRT (P < 0.001). After the completion of radiotherapy, the mean xerostomia scores at each follow-up were significantly lower in the patients who had received IMRT, compared to 3DCRT. At 7 months of completion of treatment, the mean score of xerostomia in the 3DCRT arm was 44.4, compared to 33.8 in the IMRT arm (P = 0.023). On multivariate analysis, Dmin, V30, V40, V45, V60, history of substance abuse, advanced age, and lower body weight were found to be associated with higher chances of xerostomia.Conclusion: Compared to 3DCRT, IMRT results in lower rates of xerostomia based on dosimetric as well as subjective analysis.

Comparison of Dosimetric Parameters of Three- Dimensional Conformal Radiotherapy and Intensity- Modulated Radiotherapy in Breast Cancer Patients Undergoing Adjuvant Radiotherapy after Modified Radical Mastectomy

Introduction Adjuvant radiotherapy has an important role in preventing locoregional recurrences. But radiation-induced late sequelae have become an important area of concern. The ideal postmastectomy radiotherapy technique is an area of controversy. The present study was designed to compare two widely practiced conformal techniques, three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT), in terms of dosimetry. Material and Methods A total of 50 postmodified radical mastectomy patients were selected and were randomized to treatment either by 3DCRT or IMRT technique. Two opposing tangential beams were used in 3DCRT plans whereas five to seven tangential beams were used for IMRT plans. The prescribed dose was 50 Gy in 25 fractions over 5 weeks. The dosimetric parameters were compared for planning target volume (PTV), lungs, heart, and left ventricle, opposite breast and esophagus. Results The dosimetric parameters of PTV in terms of D95%, D90%, D50%, and Dmean showed no significant difference among both techniques. The IMRT technique had significantly better mean values of Dnear-min/D98% (45.56 vs. 37.92 Gy; p = 0.01) and Dnear-max/D2% (51.47 vs. 53.65 Gy; p &lt; 0.001). Also, conformity index (1.07 vs. 1.29; p = 0.004) and homogeneity index (0.22 vs. 0.46; p = 0.003) were significantly better in IMRT arm. The dosimetric parameters of ipsilateral lung were significantly higher in IMRT arm in terms of mean dose (19.92 vs. 14.69 Gy; p &lt; 0.001) and low/medium dose regions (V5, V10, V13, V15, V20; p &lt; 0.05). However, high-dose regions (V40) were significantly higher in 3DCRT arm (15.57 vs. 19.89 Gy; p = 0.02). In contralateral lung also, mean dose was significantly higher in IMRT technique (3.63 vs. 0.53 Gy; p &lt; 0.0001) along with low-dose regions (V5, V10, V13, V15; p &lt; 0.05) while V20 was comparable between both the arms. In left-sided patients, the heart dose favored 3DCRT technique in terms of mean dose (17.33 vs. 8.51 Gy; p = 0.003), low/medium dose regions (V5, V10, V20; p &lt; 0.05), and doses to partial/whole volumes (D33, D67, D100). But the high-dose regions (V25, V30, V40) were comparable between both the arms. The dosimetry of left ventricle also showed significantly lesser values of mean dose and V5 in 3DCRT technique (p &lt; 0.0001). The opposite breast also showed higher mean dose with IMRT technique (2.60 vs. 1.47 Gy; p = 0.009) along with higher V5 (11.60 vs. 3.83 Gy; p = 0.001). The dosimetric parameters of esophagus showed higher mean dose in IMRT technique (10.04 vs. 3.24 Gy; p &lt; 0.0001) but the high-dose regions V35 and V50 were comparable between both the arms. Conclusion A clear advantage could not be demonstrated with any of the techniques. The IMRT technique led to more conformal and homogenous dose distribution with reduction in high-dose regions in ipsilateral lung while the 3DCRT technique showed lesser mean dose to organs at risk (OARs). The exposure of large volumes of OARs to low doses in IMRT technique may translate to increased long-term radiation-induced complications. The shortcomings of 3DCRT technique can be overcome by using multiple subfields within tangential fields.

Durability of the parotid-sparing effect of intensity-modulated radiotherapy (IMRT) in early stage nasopharyngeal carcinoma: A 15-year follow-up of a randomized prospective study of IMRT versus two-dimensional radiotherapy.

The durability of improved xerostomia with intensity-modulated radiotherapy (IMRT) in patients with early stage nasopharyngeal carcinoma (NPC) is uncertain. We conducted a long-term prospective assessment of participants treated with IMRT or two-dimensional radiotherapy (2DRT) in a prior randomized study. Parent study participants (IMRT, n = 28; 2DRT, n = 28) who were free of second malignancy or recurrence were eligible. Long-term radiotherapy-related toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Long-term patient-reported outcomes were assessed by the six-item xerostomia (XQ) and two European Organisation for Research and Treatment of Cancer (EORTC) questionnaires (QLQ-C30, QLQ-H&N35). Overall survival (OS), locoregional relapse-free survival (LRFS), distant relapse-free survival (DRFS), and the rate of symptomatic late complications (SLCs) were estimated for the entire cohort (n = 56). Totally, 21 (IMRT, n = 10; 2DRT, n = 11) patients gave consent and were assessed for an overall median follow-up of 15.5 years. There was significantly less RTOG ≥grade 2 xerostomia with IMRT versus 2DRT (20% vs. 90%; p = 0.001), but no significant difference in XQ scores. Patients in the IMRT arm reported lower mean scores for the "dry mouth" domain of EORTC QLQ-H&N35 (p = 0.02) and showed trends toward better 15-year OS (81.5% vs. 53.8%, p = 0.06), LRFS (70.6% vs. 53.8%, p = 0.38), and DRFS (81.5% vs. 53.8%, p = 0.07). SLCs were more frequent in the 2DRT arm. The parotid-sparing effect of IMRT in NPC treatment is durable, with significantly less physician- and patient-scored xerostomia at 15 years. IMRT results in better long-term survival and fewer SLCs.

Impact of Pelvic Intensity-modulated Radiotherapy (IMRT) on Lymph Node Coverage and Dose to Critical Organs, Compare to Three-Dimensional Conformal Radiation Therapy (3D-CRT), in Localized High-Risk Prostate Cancer

Men with high risk prostate cancer (HR-PrCa) are typically treated with combined androgen deprivation therapy and curative radiotherapy (RT) consisting of pelvic nodal and prostate/seminal vesicle (PrSV) irradiation followed by PrSV boost RT. 3D-CRT or IMRT are used for the treatment of pelvic nodes. A phase II randomized study examining the effect of RT technique on patient Quality of Life (QoL) was completed in our institution. Here, we report an early analysis of the dosimetric impact of 3D-CRT versus IMRT in patients participating in this study. A total of 105 men with HR-PrCa were randomized at 1:1 ratio to receive either pelvic 3D-CRT (standard 4-field conformal technique) or multi-beam IMRT, consisting of 4500cGy in 25 fractions to planning target volume (PTV) 1, followed by boost RT to PTV2 of 2496cGy in 13 fractions. The latter was delivered using a 7-field IMRT in all patients. Organs at risk (OAR) and clinical target volumes (CTV) were delineated on CT simulation images. The lymph node target included the common, internal, external iliac, obturator and pre-sacral lymph nodes in accordance with RTOG guidelines. CTV1 consisted of nodal CTV plus PrSV. CTV2 was minimized to PrSV. The PTV consisted of an expansion of 7 mm beyond CTV. For consistency, in comparison between the two techniques, IMRT fields were modified to results to similar superior border coverage as 3D-CRT, at the level of L5-S1. Bladder and rectum were contoured as solid organs. To take inter-fractional bowel motion into account, bowel was delineated as whole pelvic and abdominal cavity excluding bones, muscle, and other OAR. Pelvic RT with 3DCRT missed significant percentage of pelvic nodal volume. PTV1 D95% showed mean difference of -4.96, 95% CI (-6.41, -1.74); p = 0.0013 and D99% showed mean difference of -11.56, 95% CI (-14.96, -8.17); p< 0.00001 in favor of IMRT. There was significant difference in PTV1 heterogeneity index (D2%-D95%/D50%) (Mean diff = 0.22, 95%CI (0.14, 0.29); P<0.00001). IMRT decreased dose to OAR. Rectum V30 was 97% in 3DCRT compare to 93.41% in IMRT arm with absolute difference of 3.81% (95% CI (1.52, 6.11); P = 0.0014). Bladder V40 and V50 were significantly reduced (V40: 84 % vs 62% for 3DCRT vs IMRT, absolute difference of 22% (95%, CI (15.55, 28.2); P<0.0001); V50 absolute reduction of 18% with IMRT (95%, CI (11.53, 24.48); P<0.0001). Similarly, IMRT reduced total body/bone irradiation significantly. This randomized study of 3D-CRT versus pelvic IMRT is an appropriate setting to investigate the dosimetric impact of pelvic IMRT and help define its potential benefits on patient QoL. This early analysis suggests that utilization of IMRT for pelvic RT could offer dosimetric advantages by improve lymph node coverage and reducing RT dose to OAR. The results are in agreement with an improved bowel-related QoL observed in this study. On-going analysis examines correlations between dosimetric and patient QoL data.

Postoperative radiotherapy with intensity-modulated radiation therapy versus 3-dimensional conformal radiotherapy in early breast cancer: A randomized clinical trial of KROG 15-03

PurposeTo investigate the safety and efficacy of intensity-modulated radiation therapy (IMRT) for early breast cancer compared with 3-dimensional conformal radiotherapy (3D-CRT) in a prospective and randomized trial. Methods and materialsFrom March 2015 to February 2018, 693 patients with pT1-2N0M0 early breast cancer who underwent breast-conserving surgery were enrolled and randomly assigned into IMRT and 3D-CRT. The primary endpoint was 3-year locoregional recurrence-free survival (LRRFS). The secondary endpoints were recurrence-free survival, overall survival, acute toxicity, target coverage index, irradiation dose to organs at risk, and fatigue inventory. The radiation dose for the 3D-CRT arm was 59.4 Gy in 33 fractions for 6.5 weeks. It was 57.4 Gy in 28 fractions with simultaneous integrated boost for 5.5 weeks for the IMRT arm. ResultsOf 693 patients, 349 and 344 patients received 3D-CRT and IMRT, respectively. There was no significant difference in LRRFS between the two arms. Conformity index of planning target volume was significantly superior in the IMRT arm than the 3D-CRT arm (p < 0.001). The mean lung dose and V5-V50 for the ipsilateral lung were significantly lower in the IMRT arm than the 3D-CRT arm (all p < 0.05). The incidence of grade 2 or higher dermatitis was significantly lower in the IMRT arm (p = 0.009). ConclusionCompared to 3D-CRT, IMRT showed similar results in locoregional tumor control but superior results in planning target volume coverage. When IMRT is used in breast cancer, the irradiation dose to an ipsilateral lung and skin toxicity can be reduced.

Endoscopic Surgery Compared with Intensity-Modulated Radiotherapy in Resectable Locally Recurrent Nasopharyngeal Carcinoma: A Multicenter, Open-Label, Randomized Controlled Trial

Background: The role of salvage endoscopic surgery compared with intensity-modulated radiotherapy (IMRT) in the primary treatment of patients with resectable locally recurrent nasopharyngeal carcinoma (lrNPC) who had received prior radiotherapy is a matter of debate. Methods: In this multicenter, open-label, randomized controlled trial, patients with lrNPC were enrolled from 3 hospitals in southern China. The key inclusion criteria were patients pathologically diagnosed with undifferentiated or differentiated, nonkeratinizing lrNPC with tumors confined to the nasopharyngeal cavity (rT1), the postnaris or nasal septum (rT2a), the superficial parapharyngeal space (rT2b), or the base wall of the sphenoid sinus (rT3) (according to the 6 th edition American Joint Committee on Cancer (AJCC) classification). Eligible patients were randomly assigned in a 1:1 ratio to receive either endoscopic nasopharyngectomy (ENPG) or IMRT. The primary endpoint was overall survival (OS). The secondary endpoints were disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and safety. This trial was prospectively registered at the Chinese Clinical Trial Registry, number ChiCTR-TRC-11001573. Findings: Between September 30, 2011, and January 16, 2017, 200 eligible patients were randomly assigned to receive ENPG (n= 100) or IMRT (n= 100). At a median follow-up of 56.0 (95% confidence interval [CI] 51.4 - 60.6) months, the 3-year OS was 85.8% in the ENPG arm and 68.0% in the IMRT arm (hazard ratio [HR] 0.47; 95% CI, 0.29 to 0.76; P = 0.002). The DFS, LRRFS, and DMFS at 3 years for the ENPG arm and IMRT arm were 76.5% and 56.5% (HR 0.54; 95% CI, 0.36-0.81; P = 0.003), 89.8% and 79.4% (HR 0.49; 95% CI, 0.25-0.96; P = 0.033) and 94.4% and 91.4% (HR 0.87; 95% CI, 0.35-2.20; P = 0.774), respectively. The incidence of grade ≥3 radiation-related adverse events was 13.1% in the ENPG group and 36.6% in the IMRT group. Interpretation: Endoscopic surgery significantly improved OS compared with IMRT in patients with resectable lrNPC. Trial Registration: This trial was prospectively registered at the Chinese Clinical Trial Registry, number ChiCTR-TRC-11001573. Funding Statement: Sun Yat-sen University Clinical Research 5010 Program (2010004), National Natural Science Foundation of China (NSFC) grants (81900918, 81870696, 81670902), Guangdong Natural Science Foundation of China grants (2018B030312008, 2018A030313667), Guangzhou Science and Technology Project of China grant (201704020098, 201605030003), Sun Yat-sen University Young Teacher Cultivation Program (19ykpy68). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The institutional ethics review board approved the trial protocol. The trial was performed in accordance with the Declaration of Helsinki, and the results are reported according to the CONSORT statement. All participants provided written informed consent.

Intensity-modulated radiation therapy versus three-dimensional conformal radiotherapy in head and neck squamous cell carcinoma: long-term and mature outcomes of a prospective randomized trial

PurposeTo compare long-term disease-related outcomes and late radiation morbidity between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in head and neck squamous cell carcinoma (HNSCC) in the setting of a prospective randomized controlled trial.MethodsPreviously untreated patients with early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx (T1-T3, N0-N2b, M0) planned for comprehensive irradiation of primary site and bilateral neck nodes were randomly assigned to either IMRT or 3D-CRT after written informed consent. Patients were treated with 6MV photons to a total dose of 70Gy/35 fractions over 7 weeks (3D-CRT) or 66Gy/30 fractions over 6 weeks (IMRT). A sample size of 60 patients was estimated to demonstrate 35% absolute difference in the incidence of ≥grade 2 acute xerostomia between the two arms. All time-to-event outcomes were calculated from date of randomization until the defined event using the Kaplan-Meier method.ResultsAt a median follow-up of 140 months for surviving patients, 10-year Kaplan-Meier estimates of loco-regional control (LRC); progression-free survival (PFS); and overall survival (OS) with 95% confidence interval (95%CI) were 73.6% (95%CI: 61.2–86%); 45.2% (95%CI: 32–58.4%); and 50.3% (95%CI: 37.1–63.5%) respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRC [79.2% (95%CI: 62.2–96.2%) vs 68.7% (95%CI: 51.1–86.3%), p = 0.39]; PFS [41.3% (95%CI: 22.3–60.3%) vs 48.6% (95%CI: 30.6–66.6%), p = 0.59]; or OS [44.9% (95%CI: 25.7–64.1%) vs 55.0% (95%CI: 37–73%), p = 0.49]. Significantly lesser proportion of patients in the IMRT arm experienced ≥grade 2 late xerostomia and subcutaneous fibrosis at all time-points. However, at longer follow-up, fewer patients remained evaluable for late radiation toxicity reducing statistical power and precision.ConclusionsIMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC.

Concurrent cisplatin and dose escalation with intensity-modulated radiotherapy (IMRT) versus conventional radiotherapy for locally advanced head and neck squamous cell carcinomas (HNSCC): GORTEC 2004-01 randomized phase III trial

BackgroundConcurrent 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. MethodsPatients 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). Results188 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. ConclusionDose-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.

Retrospective analysis of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy of postoperative treatment for biliary tract cancer

PurposeThis study was conducted to compare the outcome of three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for the postoperative treatment of biliary tract cancer.Materials and MethodsFrom February 2008 to June 2016, 57 patients of biliary tract cancer treated with curative surgery followed by postoperative 3D-CRT (n = 27) or IMRT (n = 30) were retrospectively enrolled.ResultsMedian follow-up time was 23.6 months (range, 5.2 to 97.6 months) for all patients and 38.4 months (range, 27.0 to 89.2 months) for survivors. Two-year recurrence-free survival is higher in IMRT arm than 3D-CRT arm with a marginal significance (25.9% vs. 47.4%; p = 0.088). Locoregional recurrence-free survival (64.3% vs. 81.7%; p = 0.122) and distant metastasis-free survival (40.3% vs. 55.8%; p = 0.234) at two years did not show any statistical difference between two radiation modalities. In the multivariate analysis, extrahepatic cholangiocarcinoma, poorly-differentiated histologic grade, and higher stage were significant poor prognostic factors for survival. Severe treatment-related toxicity was not significantly different between two arms.conclusionsIMRT showed comparable results with 3D-CRT in terms of recurrence, and survival, and radiotherapy toxicity for the postoperative treatment of biliary tract cancer.