3DCRT Arm Research Articles

Helical Tomotherapy Versus 3-Dimensional Conformal Radiation Therapy in High-Risk Prostate Cancer: A Phase 3 Randomized Controlled Trial

We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer. Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions. RT was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity. Overall,123 patients were randomly assigned to either the 3D-CRT (n = 60) or tomotherapy (n = 63) arms. The median follow-up was 161 months. Overall, the proportion of patients with grade ≥ 2 late rectal toxicity was 8.3% (95% CI, 3.1-19.1; n = 5) in the 3D-CRT arm and 11.1% (95% CI, 5.0-22.2; n = 7) in the tomotherapy arm with no significant between-arm difference (P = .83). There was no significant difference (P = .17) in the proportion of patients with late grade ≥ 2 genitourinary toxicity:10.0% (95% CI, 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI, 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the 2 groups (hazard ratio for the tomotherapy arm: 0.72; 95% CI, 0.46-1.15; P = .17). In this phase 3 trial, the overall incidence of grade ≥ 2 rectal toxicity was low and was not significantly different between the 2 arms. There was no significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates.

Effect of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in locally advanced rectal cancer

Background: Rectal carcinoma is a prevalent clinical condition, and treatment hinges on factors like tumor specifics, staging, grading, and histopathological characteristics. While surgery remains the primary treatment, neoadjuvant chemoradiotherapy, particularly using 3D-CRT, has proven effective in reducing local recurrence rates for locally advanced cases. Alternatively, 2D-RT is considered for neoadjuvant treatment. This study aimed to compare the impact of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in the context of locally advanced rectal cancer. Methods: In this multicentre quasi-experimental study, 60 patients with biopsy-proven adenocarcinoma and clinically confirmed locally advanced rectal cancer, were divided into Group A (receiving oral capecitabine with three-dimensional conformal radiotherapy) and Group B (receiving the same capecitabine dose with 50 Gy two-dimensional radiotherapy). After surgery within 6-12 weeks, outcomes were analysed. Results: After neoadjuvant chemoradiotherapy, clinical complete response rates were 16.7% in Group A and 10.0% in Group B, with a higher pathological complete response in Group A (10.0% vs. 3.3%). Tumor downsizing occurred in 83.3% of Group A and 73.3% of Group B, and sphincter-sparing surgery was achieved in 73.3% of Group A and 56.7% of Group B. Grade 2 toxicities included anemia (10.0% vs. 13.3%), leucopenia (13.3% vs. 20.0%), diarrhoea (10.0% vs. 16.7%), proctitis (13.3% vs. 40.0%), and urinary toxicity (10.0% vs. 20.0%). Grade-1 toxicities were nausea (20.0% vs. 40.0%), vomiting (20.0% vs. 36.7%), mucositis (56.7% vs. 60.0%), hand-foot syndrome (33.3% vs. 40.0%), and urinary toxicity (43.3% vs. 56.67%), with significant proctitis in Group A (p=0.012). Other toxicities showed non-significant p-values (>0.05). Conclusions: Tumour response was not statistically significant between the patients of concurrent 3D-CRT and 2D-RT Arms. But the patients of 3D-CRT arm showed better response arithmetically. Also, there was an observable significant reduction of toxicities (lower gastrointestinal) in the 3D-CRT arm.

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.

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.

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.

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.

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.

Dosimetric analysis and acute toxicity comparison of bone marrow sparing intensity-modulated radiation therapy versus three-dimensional conformal therapy with concurrent chemotherapy for the treatment of cervical carcinoma: A prospective single institutional study

Background: The aim of the study was to compare the dosimetry and acute toxicities of bone marrow sparing intensity-modulated radiation therapy (BMS-IMRT) and three-dimensional conformal radiation techniques (3DCRT) in locally advanced cervical cancer. Materials and Methods: This is a hospital-based prospective randomized study and histologically proven locally advanced cervical carcinoma patients were selected for the analysis. A total of thirty patients were equally allocated in the two treatment arms: BMS-IMRT and 3DCRT. External beam radiation therapy was delivered to a dose of 50 Gy/25# followed by high dose rate brachytherapy along with concurrent chemotherapy. The target volumes and the organs at risks were delineated. The BM comprised pelvic BM (PBM); lumbosacral BM (LSBM); ilium BM (IBM) and Ischium, Pubis and Pelvic femora together constituting lower PBM (LPBM). Results: BMS-IMRT was superior to the 3DCRT arm in reducing the dose to the PBM, small bowel, rectum, and bladder. On comparison of the BM dose volume histogram, the P value was significant (BMS IMRT vs. 3DCRT) in the higher dose range (30 and 40 Gy) for the IBM, LPBM, and whole pelvis BM. However, the difference in the low-dose irradiation (10 and 20 Gy) region was not significant. Furthermore, in the LSBM region, BMS IMRT was superior at all dose levels with no significant P value. Acute toxicities were higher in the 3DCRT arm. Conclusion: Thus, BMS-IMRT resulted in significant reduction of dose to the PBM. This can help in reducing the hematologic toxicities associated with pelvic radiation.

Early Clinical Outcomes and Dosimetric Evaluation in Post Mastectomy Radiotherapy in Locally Advanced Breast Cancer: A Phase II Open Label Randomized Study between 3DCRT and VMAT

Post mastectomy Radiation (PMRT) is indicated as adjuvant treatment in the multimodality management of Locally Advanced Breast Cancer (LABC). Three-Dimensional Conformal Radiation (3DCRT) for PMRT is used with tangential fields for better target coverage and sparing of organs at risk (OAR). In comparison, VMAT has the potential to improve the coverage and decrease the OAR doses. We prospectively conducted a phase II randomized study comparing 3DCRT (Arm A) and VMAT (Arm B) in PMRT with regional nodal irradiation (RNI) to evaluate dosimetric and clinical differences between the two modalities. Women aged ≥ 18 years with locally advanced breast cancer undergoing MRM were recruited in the study. Forty patients were accrued after Institutional Ethics Committee approval. Contouring was done as per the standard RTOG guidelines. For 3DCRT, Planning was done with single isocenter technique. Two tangential fields with field in field were used for PTV-CW and AP-PA fields with higher AP weightage were used to cover PTV-RNI. For VMAT, two small partial arcs were used. The dose prescribed was 50 Gy in 25 fractions over 5 weeks. Contouring and planning was done on MONACO treatment planning system. Dosimetric analysis was done and compared between the arms. Clinical acute toxicity, late toxicity was noted with RTOG acute toxicity criteria. Quality of life (QOL) was assessed with EORTC BR 23 questionnaire. Statistical analysis was done with SPSS v 21 with chi square test and p-value < 0.05 was considered as significant. Between Jan 2018 to March 2019, forty patients were accrued in the study and twenty patients were randomized to each arm. All patients received planned allocated treatment and were eligible for analysis. PTV CW coverage was similar in both the arms. PTV RNI V95 coverage were better in VMAT arm (97.8%) than 3DCRT arm (94.5%) (p = <0.001). The ipsilateral lung V5 and V20 was 51.6% and 24.7% for VMAT and 47.1% and 27.8% for 3DCRT (p = 0.0185 and p = 0.167). The thyroid V45 was 51.3% for 3DCRT and 42% for VMAT arm (p = 0.018)]. The heart Dmean for 3DCRT and VMAT was 4.3Gy and 6.5Gy (p = 0.0372). There was no significant difference in skin, subcutaneous, lymphedema or lung toxicity between the two arms at 1, 3, and 6 months. There was no difference in global health status and QOL between two arms at 1, 3, and 6 months. No loco-regional recurrence was noted at 6 months. VMAT provides better coverage to lymph nodes with potential to decrease ipsilateral lung dose. The clinical acute toxicity, late toxicity and QOL was similar with VMAT and 3DCRT. A large prospective trial and longer follow-up is needed to confirm the findings.

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.

Patient Perceptions in a Nonblinded Randomized Trial of Radiation Therapy Technologies: A Novel Survey Study Exploring Therapeutic Misconception

Therapeutic misconception is the tendency for a clinical trial participant to overlook the scientific objective of a clinical trial and instead believe that an experimental intervention is intended for personal therapeutic benefit. We sought to evaluate this tendency in the setting of a clinical trial of a new radiation therapy technology. Patients with left-sided, node positive breast cancer enrolled in a randomized clinical trial evaluating intensity modulated radiation therapy with deep inspiration breath hold (IMRT-DIBH) versus 3-dimensional conformal radiation therapy (3DCRT). Patients who enrolled completed surveys at baseline, after randomization, and upon completion of radiation therapy to evaluate expectations, satisfaction, and experiences. Forty women participated in the survey study, with 20 in each arm. Most participants endorsed the perception that participation in the trial might result in better treatment than the current standard treatment (77%) and more medical attention than being off trial (54%). At baseline, most women (74%) believed that a new treatment technology is superior than an established one. Before randomization, 43% of participants believed IMRT-DIBH would be more effective than standard treatment with 3DCRT, none believed that 3DCRT would be more effective, 23% believed that they would be the same, and 34% did not know. None believed that IMRT-DIBH would cause worse long-term side effects, whereas 37% thought that 3DCRT would. Most (71%) reported that they would choose to be treated with IMRT-DIBH; none would have elected 3DCRT if given a choice. Nearly half (44%) in the 3DCRT arm wished that they had been assigned to the IMRT-DIBH arm; none in the IMRT-DIBH arm expressed a wish for crossover. Most participants reported the perception that trial participation would result in better treatment and more medical attention than off trial, hallmarks of therapeutic misconception. Our observations provide empirical evidence of a fixed belief in the superiority of new technology and highlight the importance of adjusting expectations through informed consent to mitigate therapeutic misconception.

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.

Dosimetric comparison and clinical correlation between conventional four field radiotherapy versus three-dimensional conformal radiotherapy in cancer cervix

Introduction: With sectional imaging, wide variations are reported in pelvic anatomy of individual patients raising concerns over adequate coverage of target volume with conventional radiotherapy based on standard bony landmarks. Three-dimensional conformal radiotherapy (3DCRT) is reported to decrease normal tissue toxicity, along with decrease in chances of geographic miss. Present study is done for dosimetric comparison of Planning Target Volume (PTV) and Organs at Risk (OAR) in cancer cervix patients treated with conventional and conformal radiotherapy along with clinical correlation in terms of side effects and tumor response. Materials and Methods: Fifty patients of cancer cervix underwent planning contrast enhanced CT scan. Target volumes & OAR were contoured. Patients were randomized into conventional & conformal arms. Conventional fields were planned using standard bony landmarks. CT based radiotherapy planning was done for 3DCRT arm. Field sizes &dose volume histogram (DVH) were recorded & compared for target coverage & OAR sparing in both arms. All patients received concurrent chemotherapy followed by brachytherapy. Results: Field sizes used for the 3DCRT plans were significantly larger than those used for the conventional plans (p= 0.000). Optimal PTV coverage was significantly improved using 3DCRT as compared to conventional radiotherapy (p= 0.0001). Dose homogeneity in both arms were almost similar (p= 0.292), while conformity index was better in 3DCRT which was statistically significant between the groups (p= 0.000). Mean dose to the Planning Target Volume was increased significantly in the CT based plan when compared with the standard four field plan (p= 0.0001).Difference in doses to the organs at risk (urinary bladder, and small bowel)and their side effects were statistically significant across both groups. There was no difference in tumor response. Conclusion: The present study showed significantly better target volume coverage & dose homogeneity with 3DCRT which may translate into better local control & survival but longer follow up is required to validate it.

Bone density and pain response following intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for vertebral metastases - secondary results of a randomized trial

BackgroundThis was a prespecified secondary analysis of a randomized trial that analyzed bone density and pain response following fractionated intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) for palliative management of spinal metastases.Methods/materialsSixty patients were enrolled in the single-institutional randomized exploratory trial, randomly assigned to receive IMRT or 3DCRT (30 Gy in 10 fractions). Along with pain response (measured by the Visual Analog Scale (VAS) and Chow criteria), quantitative bone density was evaluated at baseline, 3, and 6 months in both irradiated and unirradiated spinal bodies, along with rates of pathologic fractures and vertebral compression fractures.ResultsRelative to baseline, bone density increased at 3 and 6 months following IMRT by a median of 24.8% and 33.8%, respectively (p < 0.01 and p = 0.048). These figures in the 3DCRT cohort were 18.5% and 48.4%, respectively (p < 0.01 for both). There were no statistical differences in bone density between IMRT and 3DCRT at 3 (p = 0.723) or 6 months (p = 0.341). Subgroup analysis of osteolytic and osteoblastic metastases showed no differences between groups; however, mixed metastases showed an increase in bone density over baseline in the IMRT (but not 3DCRT) arm. The 3-month rate of the pathological fractures was 15.0% in the IMRT arm vs. 10.5% in the 3DCRT arm. There were no differences in pathological fractures at 3 (p = 0.676) and 6 (p = 1.000) months. The IMRT arm showed improved VAS scores at 3 (p = 0.037) but not 6 months (p = 0.430). Using Chow criteria, pain response was similar at both 3 (p = 0.395) and 6 (p = 0.732) months.ConclusionsThis the first prospective investigation evaluating the impact of IMRT vs. 3DCRT on bone density. Along with pain response and pathologic fracture rates, significant rises in bone density after 3 and 6 months were similar in both cohorts. Future randomized investigations with larger sample sizes are recommended.Trial registrationNCT, NCT02832830. Registered 14 July 2016

Local response and pathologic fractures following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy for spinal metastases - a randomized controlled trial

BackgroundThis was a prespecified secondary analysis of a randomized trial, which analyzed bone density following stereotactic body radiotherapy (SBRT) versus conventional three-dimensional conformal radiotherapy (3DCRT) as part of palliative management of painful spinal metastases.MethodsFifty-five patients were enrolled in this single-institutional randomized exploratory trial (NCT02358720). Participants were randomly assigned to receive SBRT (single-fraction 24 Gy) or 3DCRT (30 Gy/10 fractions). Quantitative bone density was evaluated at baseline, 3 and 6 months in both irradiated and unirradiated spinal bodies, along with rates of pathologic fractures and vertebral compression fractures.ResultsAs compared to baseline, bone density became significantly higher at 3 and 6 months following SBRT by a median of 33.8% and 72.1%, respectively (p < 0.01 for both). These figures in the 3DCRT cohort were 32.9% and 41.2%, respectively (p < 0.01 for both). There were no statistical differences in bone density between SBRT and 3DCRT at 3 (p = 0.629) or 6 months (p = 0.327). Subgroup analysis of osteolytic metastases showed an increase in bone density relative to baseline in the SBRT (but not 3DCRT) arm. Bone density in unaffected vertebrae did not show substantial changes in either group. The 3-month incidence of new pathological fractures was 8.7% in the SBRT arm vs. 4.3% in the 3DCRT arm.ConclusionsDespite high ablative doses in the SBRT arm, the significant increase in bone density after 3 and 6 months was similar to that of 3DCRT. Our trial demonstrated a moderate rate of subsequent pathological fracture after SBRT. Future randomized investigations with larger sample sizes are recommended.Trial registrationwww.clinicaltrials.gov: NCT02358720 on 9nd of February 2015.

Three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy in carcinoma cervix

Background: Cervical cancer is the most common gynecological cancer among Indian women. 3D-CRT treatment is associated with more acute and late toxicities, because of close proximity of bladder and rectum to the cervix. The newer technique like IMRT is associated with less toxicities. Our study is to compare 3D-CRT and IMRT in terms of dosimetric parameters, toxicities and clinical outcomes. Methods: From February 2015 to July 2016 total 40 newly diagnosed locally advanced cervical carcinoma patients were treated with concurrent chemo radiotherapy with weekly cisplatin. Those patients were randomized to arm A - 3D-CRT and arm B - IMRT. Results: The dosimetric parameters of the bladder, rectum, bowel bag, and pelvic bone marrow were significantly decreased in the IMRT arm as compared to 3DCRT arm except for V30, V50 of bowel bag and V50 of pelvic bone marrow. The acute and late toxicities were similar among both arms. All the patients were assessed for treatment response at 6 weeks after completion of the treatment. All achieved complete clinical response. Out of 40 patients only one had brain metastasis after a median follow up of 18 months. Conclusions: Though IMRT showed dosimetric reduction compared to 3D-CRT but it did not showed any clinical benefit. At present scenario in developing countries like India where the cancer centers are over loaded with the carcinoma cervix cases can be treated with the 3D-CRT technique without compromising clinical outcomes.

Choice of appropriate beam model and gantry rotational angle for low-dose gradient-based craniospinal irradiation using volumetric-modulated arc therapy

AbstractObjectivesWe aimed to assess the impact of advanced multileaf collimator (MLC) models and flattening filter-free (3F) beam in volumetric-modulated arc therapy (VMAT)-based craniospinal irradiation (CSI).MethodsCT scans of five medulloblastoma patients who previously received CSI at our hospital were used for the present study. Patients were planned for a prescription dose of 35 Gy to craniospinal axis. A three-dimensional conformal radiotherapy (3DCRT) plan and a VMAT plan using 1 cm MLC leaf width were generated as the gold standard (reference arm). Test VMAT plans were generated using Agility MLC model (MLC leaf width 5 mm) for various combinations of flattened beam (F) and 3F beam for treating the brain and spine planning target volume (PTV). Organs at risks (OARs) were analysed for dose 5, 50, 75 and 90% volumes, mean dose and maximum dose.ResultsAll 3DCRT plans and VMAT plans were aimed to cover 95% of PTV by at least 95% prescription dose. VMAT demonstrated lesser dose spillage than 3DCRT to body volume minus PTV (NTID: non tumor integral dose) for a dose threshold above 7·5 Gy. For the low-dose range (1–7 Gy), variation between the dose coverage between all VMAT plans (for either spine or brain PTV) was &lt;1%. Intra-VMAT plan dose variation for all OAR’s for all tested parameters was &lt;1 Gy. Average monitor unit (MU) difference among different VMAT plans ranged between 1·52 and 2·13 when normalised to 3DCRT MU. For VMAT plans, flat beam with 1 cm MLC showed the highest MU, whereas Agility MLC with 3F beam had the least MU values for intra-VMAT plans. No statistical significance variation (p) was observed in between reference arm and test arm plans except for mean dose and V107% for PTV spine. When compared between reference arm 3DCRT and test arm VMAT plans. For OAR’s, no statistical difference was observed between reference and test arm VMAT plans.ConclusionsReference arm plans and test arm plans exhibit no statistically significant difference. However, as compared with 3DCRT, VMAT plans are more conformal and produce lesser dose to OAR at the cost of higher delivered MU. 3F beams or finer width MLC’s (width &lt;5 mm) have no advantage over the conventional 1 cm MLC and flat beam except that 3F beams have a shorter beam delivery time. This study demonstrate a significantly lesser spillage dose to NTID/body that of the reported literature, which is attributed to limited rotational arc length used for VMAT plans.