3D-CRT Group Research Articles

Ultra-hypofractionated whole breast adjuvant radiotherapy in the real-world setting: single experience with 271 elderly/frail patients treated with 3D and IMRT technique.

PurposeThe purpose of the study was to evaluate the toxicity, local control, overall and disease-free survival of elderly breast cancer (BC) patients treated with adjuvant once-weekly ultra-hypofractionated radiotherapy (RT) either with intensity-modulated RT (IMRT) or 3D conformal RT (3DCRT).MethodsFrom July 2011 to July 2018, BC patients receiving 5.7 Gy once a week for 5 weeks to the whole breast after breast-conserving surgery were considered for the study. Inclusion criteria were: T1–T3 invasive BC, no or limited axillary involvement, age ≥ 65 years or women with commuting difficulties or disabling diseases.ResultsA total of 271 patients were included in the study. Median age was 76 (46–86) years. Most of BC were T1 (77%), while the remaining were T2 (22.2%) and T3 (0.4%). Axillary status was negative in 68.3% of the patients. The only severe acute toxicity (G3) at the end of RT was erythema (0.4%), registered in the 3DCRT group; no G3 edema or epitheliolysis was recorded. With 18 months of median follow-up, severe early–late toxicity (G3) was reported in terms of fibrosis and breast retraction, both with an incidence of 1.4%, mostly in the 3DCRT group. Oncological outcomes at a median follow-up of 2.9 years reported 249/271 (91.9%) patients alive and free from any event and 5 (1.8%) isolated locoregional recurrences. At 3 years, disease-free survival and overall survival were 94.9% and 97.8%, respectively. Breast volume > 500 cm3 was reported as predictive for moderate–severe (≥ G2) acute toxicity.ConclusionsWeekly ultra-hypofractionated whole breast RT seems feasible and effective. Toxicity was mild, local control was acceptable, and overall survival was 97.8% at 3 years. Rates of severe toxicity were reduced with the IMRT technique.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00432-021-03907-w.

Short-term effectiveness and safety of CT-guided radioactive iodine-125 seed implantation for treatment of adrenal metastases.

PurposeTo evaluate short-term effectiveness and safety of computed tomography (CT)-guided radioactive iodine-125 (125I) seed implantation (CTRISI) for treating adrenal metastases.Material and methodsA total of 50 consecutive patients with adrenal metastases were enrolled retrospectively. Among them, 18 patients received CTRISI, and 18 received 3D-conformal radiotherapy (3D-CRT) treatment. The remaining 14 patients without any treatments served as a control group. Follow-up CT was performed at 6 weeks, 3 months, and 6 months after treatment. Tumor responses and complications were evaluated.ResultsAt 6 weeks, control rate in control group (complete response [CR] + partial response [PR]) was 0, and in the CTRISI group (CR + PR, 84.41%), it was significantly higher than that in the 3D-CRT group (CR + PR, 44.44%). Local control rates with CTRISI at 3 and 6 months were 68.42% and 57.89%, respectively. No severe complications were observed after CTRISI.ConclusionsCTRISI is an effective and safe method for short-term treatment of adrenal metastases. Our findings suggest that CTRISI can safely and effectively be used for adrenal metastases patients as short-term treatment. Further survival studies with longer follow-up are warranted to validate our results.

COMPARISON OF TOXICITY PROFILES AMONG HEAD & NECK CANCER PATIENTS UNDERGOING 3D CRT, IMRT & IGRT MODES OF RADIOTHERAPY

Introduction: Radiotherapy is the one of the main modes of treating oral cancer and in recent days radiation delivery and beam shaping is evolving with novel methods. Some of the methods of radiation delivery include Three dimensional conformal radiotherapy(3D CRT), Intensity Modulated Radiotherapy ( IMRT), Image Guided Radiotherapy ( IGRT), stereotactic body radiotherapy and proton beam therapy to name a few. However these techniques are always associated with some pitfalls such as mucositis, skin reactions, dysphagia and xerostomia which occur in both acute and chronic manner. Hence there is a continuous necessity to optimize dose distribution to reduce the toxicities and have a positive impact on the quality of life of the patient. Aim: To assess and compare the toxicity proles occurring due to radiotherapy in head and neck cancer patients undergoing 3D CRT, IMRT and IGRTmodes. Materials and Methods: A total of 60 patients with a Kornofsky Performance Scale (KPS) more than 70 were included in the study. Of the 60 patients included in the study 20 were in the 3D CRT group, 20 were in the IMRT group and 20 were in the IGRT group. The patients were assessed for grade of mucositis and skin reactions in an acute and chronic manner. Results: The results showed that 3D CRT group demonstrated signicantly more acute and chronic toxicities in relation to mucositis and skin reactions when compared to IMRT and IGRT. However on comparing the toxicities between IMRT and IGRT groups there were insignicant differences. Conclusion: In our study, IMRT and IGRT were associated with a signicantly lower incidence of toxicity in relation to mucositis and skin reactions and hence they are more tissue sparing and improves the quality of life of the patient.

Potential Benefits of Volumetric Modulated Arc Therapy to Reduce the Incidence of Grade 2 Radiation Pneumonitis in Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer Patients

<h3>Purpose/Objective(s)</h3> Although the use of volumetric modulated arc therapy (VMAT) is widespread, there are few reports on the impact of using VMAT on radiation pneumonitis (RP) in radiotherapy for locally advanced non-small cell lung cancer (NSCLC) patients especially for Asians. The administration of durvalumab after radical chemoradiotherapy has been shown to improve the outcome of locally advanced NSCLC; however, it cannot be used when grade 2 or higher radiation pneumonitis occurs. Therefore, it is extremely important to identify the predictive factors of grade 2 RP. The purpose of this study was to identify the factors that caused grade 2 RP and evaluate the impact of using VMAT on the incidence of grade 2 RP in Japanese population whose risk of RP is higher than other areas. <h3>Materials/Methods</h3> We retrospectively evaluated 124 patients who underwent radical radiotherapy for locally advanced NSCLC at our hospital from 2008 to 2019. RP was evaluated using the common terminology criteria for adverse events version 5.0. In order to analyze predictive factors of grade 2 RP, the mean lung dose and V5 Gy–V70 Gy were analyzed as the lung DVH parameters. The other predictive factors for grade 2 RP examined in this study were age, gender, performance status, vital capacity (VC), forced expiratory volume in one second (FEV1.0), lung volume, Brinkman index, presence of interstitial lung disease, presence of pulmonary emphysema, CRP, KL-6, tumor site (upper/middle vs lower lobe), planning target volume (PTV), total dose (≥ 70 Gy vs < 70 Gy). Fisher's exact test and logistic regression analysis was used to compare the incidence of grade 2 RP between the two groups for univariate analysis (UVA) and multivariate analysis (MVA), respectively. <i>P</i> values < 0.05 were considered statistically significant. Predictive performance of the predictor as a continuous variable was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC). <h3>Results</h3> Eighty-four patients underwent 3D-CRT (3D-CRT group), and 40 patients underwent VMAT (VMAT group). Of the 124 cases, grade 2 or higher RP was observed in 51 cases (41.1%). The incidence of grade 2 or higher RP was significantly lower in the VMAT group compared with 3D-CRT group (25.0% vs. 48.8%, <i>P</i> = 0.0185). As for predictive factors of grade 2 RP, all lung DVH parameters were related to grade 2 RP. Among these factors, V30 which had the highest AUC value (0.787) was used as a representative value of lung DVH, and examined together with the other prognostic factors of RP in MVA. Both the UVA and MVA showed that the treatment methods (3D-CRT, <i>P</i> = 0.0097 in MVA), tumor site (lower lobe, <i>P</i> = 0.0011 in MVA), total dose (≥ 70 Gy, <i>P</i> = 0.0008 in MVA), and V_30Gy (≥ 19%, <i>P</i> < 0.0001 in MVA) were associated with grade 2 or higher RP. <h3>Conclusion</h3> We identified the predictive factors for grade 2 or higher RP in radiotherapy for locally advanced NSCLC patients. It was suggested that the use of VMAT could reduce the incidence of grade 2 RP.

Potential benefits of volumetric modulated arc therapy to reduce the incidence of ≥ grade 2 radiation pneumonitis in radiotherapy for locally advanced non-small cell lung cancer patients.

The use of volumetric modulated arc therapy is gradually widespread for locally advanced non-small cell lung cancer. The purpose of this study was to identify the factors that caused ≥ grade 2 radiation pneumonitis and evaluate the impact of using volumetric modulated arc therapy on the incidence of ≥ grade 2 radiation pneumonitis by comparing three-dimensional conformal radiation therapy. We retrospectively evaluated 124 patients who underwent radical radiotherapy for locally advanced non-small cell lung cancer in our institution between 2008 and 2019. The following variables were analysed to detect the factors that affected ≥ grade 2 radiation pneumonitis; age, sex, the presence of interstitial lung disease, pulmonary emphysema, tumour location, stage, PTV/lung volume, lung V20Gy, total dose, concurrent chemoradiotherapy, adjuvant immune checkpoint inhibitor, radiotherapy method. Radiation pneumonitis was evaluated using the common terminology criteria for adverse events (version 5.0). A total of 84 patients underwent three-dimensional conformal radiation therapy (3D-CRT group) and 40 patients underwent volumetric modulated arc therapy (VMAT group). The cumulative incidence of ≥ grade 2 radiation pneumonitis at 12months was significantly lower in the VMAT group than in the 3D-CRT group (25% vs. 49.1%). The use of volumetric modulated arc therapy was a significant factor for ≥ grade 2 radiation pneumonitis (HR:0.32, 95% CI: 0.15-0.65, P=0.0017) in addition to lung V20Gy (≥ 24%, HR:5.72 (95% CI: 2.87-11.4), P<0.0001) and total dose (≥ 70Gy, HR:2.64 (95% CI: 1.39-5.03), P=0.0031) even after adjustment by multivariate analysis. We identified factors associated with ≥ grade 2 radiation pneumonitis in radiotherapy for patients with locally advanced non-small cell lung cancer. Volumetric modulated arc therapy has potential benefits to reduce the risk of ≥ grade 2 radiation pneumonitis.

Comparison Between Dose-Escalated Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy for Salvage Radiation Therapy After Prostatectomy

PurposeTo compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy. Methods and MaterialsA total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first. ResultsThe median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively. ConclusionsDose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.

Predictors of heart and lung dose in left-sided breast cancer treated with VMAT relative to 3D-CRT: A retrospective study.

BackgroundBefore generating radiotherapy plans for breast cancer patients, the choice of plan techniques (three-dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT)) should be made. This study investigated the performance of two geometric indices in aiding the choice of 3D-CRT and VMAT plans in women undergoing left-sided whole breast radiotherapy.Materials and methods119 patients, previously treated with left-sided breast radiotherapy (61 3D-CRT treatments and 58 VMAT treatments) from a single institution, were retrospectively studied. Two geometric indices, which were cardiac junction (CJ) index and pulmonary junction (PJ) index, were defined and the relationship between these indices and dose of organs at risk (OARs) were evaluated. Two-tailed Student’s t-test was performed to compare patient characteristics between 3D-CRT and VMAT. Linear regressions were calculated to investigate the association between geometric indices and absorbed dose of heart and left lung, including mean dose of heart (MHD), V5, V30 of heart, and mean dose of left lung (MLLD), V5, V10, V20, V30, V40 of left lung.ResultsThe CJ index was strongly correlated with the MHD in 3D-CRT group and VMAT group. The linear regression formulas were MHD = 4826.59 ×CJ Index+310.48 (R = 0.857, F = 163.77, P = 0.000) in 3D-CRT plans and MHD = 1789.29×CJ Index+437.50 (R = 0.45, F = 14.23, P = 0.000) in VMAT plans. The intersection of the two formulas was CJ index = 4.2% and MHD = 512.33 cGy. The PJ index demonstrated a strongly positive correlation with MLLD in 3D-CRT group and VMAT group as well. The linear regression formulas were MLLD = 2879.54×PJ Index+999.79 (R = 0.697, F = 55.86, P = 0.000) in 3D-CRT plans and MLLD = 1411.79×PJ Index+1091.88 (R = 0.676, F = 47.11, P = 0.000) in VMAT plans, the intersection of the two formulas was PJ index = 6.3% and MLLD = 1180.46 cGy.ConclusionsCJ index and PJ index could be used as a practical tool to select 3D-CRT or VMAT before generating plans. We recommend that VMAT plan is preferable when CJ index is greater than 4.2% and/or PJ index is greater than 14.6%, while 3D-CRT plan is the first choice in the opposite.

Outcome and safety analysis of endometrial cancer patients treated with postoperative 3D-conformal radiotherapy or intensity modulated radiotherapy

Background We sought to analyze the toxicity rates and the treatment outcomes in endometrial cancer (EC) patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). Material and methods The clinical data of 646 EC patients treated with postoperative adjuvant 3DCRT (265 patients, 41%) or with IMRT (381 patients, 59%) between April 2007 and August 2019 were retrospectively analyzed. The primary endpoints were treatment-related acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary endpoints were LC and overall survival (OS) and disease-free survival (DFS). Results Median follow-up time was 37 months. The rates for acute GI and GU toxicities of any grade for the entire group were 55.6% and 46.8%, respectively. Acute grade ≥2 GI toxicity was significantly less in patients treated with IMRT compared to those treated with 3DCRT (11.0% vs. 19.2%, p=.004). However, no significant difference grade ≥2 GU toxicities was observed between the 3DCRT and IMRT groups (15.1% vs. 11.0%; p=.15). Acute grade ≥2 GI and GU toxicities were higher in patients receiving systemic chemotherapy, while paraaortic field irradiation increases only the risk of acute grade ≥2 GI toxicity. Estimated 3-year late grade ≥3 GI toxicity rates in the 3DCRT- and IMRT-treated patients were 4.6% and 1.9% (p= .03), respectively. The patients treated with adjuvant ChT had higher rates of late serious GI complications than those without adjuvant ChT. No significant difference in terms of survival and disease control was observed between the 3DCRT and IMRT treatment groups. No significant factor for LC was found in the multivariate analysis. Conclusion In this multicentric study involving one of largest patient population, we found that IMRT-treated EC patients showed comparable clinical outcomes but with a lower incidence of GI toxicities compared with those treated with 3DCRT.

Quality of Life: A Prospective Randomized Trial of Palliative Volumetric Arc Therapy Versus 3-Dimensional Conventional Radiation Therapy

Volumetric arc therapy (VMAT) is a radiation therapy (RT) technique that spares normal tissues from high and intermediate RT doses but increases the volume of tissues receiving low doses of RT compared with 3-dimensional conformal RT (3DCRT). We hypothesized that palliative VMAT would reduce the detriment to patient quality of life (QOL) compared with palliative 3DCRT. This phase 2 trial randomized patients to palliative RT using VMAT or 3DCRT to 1 painful site of metastatic disease in the trunk. Treating physicians could choose 8 Gy in 1 fraction or 20 Gy in 5 fractions to stratify randomization. The primary endpoint was the change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30) global health status QOL subscale at 1 week after RT. Repeated measures analysis of variance was used to assess the relationship of patient QOL over time with other factors. From July 2014 to November 2017, 37 patients who underwent 3DCRT and 32 patients who underwent VMAT were randomized into the study. Median overall survival was 9 months. Overall pain responses to RT were equivalent (P = .53) between the techniques. Patient compliance in returning QOL questionnaires was 94%, 81%, and 69% at baseline, 1 week after RT, and 1 month after RT, respectively. At 1 week after RT, change in global QOL was not significantly (P = .31) different between VMAT versus 3DCRT. At 4 weeks after RT, VMAT induced significantly (P = .049) less global QOL deterioration than 3DCRT did. Patients who underwent VMAT maintained better physical (P = .012), role (P = .041), and social (P = .025) functioning, but they reported more diarrhea symptoms (P = .017) than in the 3DCRT group. Palliative VMAT and 3DCRT did not differ in their ability to control pain; however, palliative VMAT induced fewer QOL detriments than 3DCRT did at 4 weeks after RT.

Intensity-modulated Radiation Therapy (IMRT) May Reduce Diarrhea With Similar Treatment Efficacy Even In Japanese Treatment Strategy For Cervical Cancers

The RTOG 1203 trial showed that IMRT after hysterectomy could reduce acute radiation enteritis (ARE) compared to 3-dimensional conformal radiotherapy (3DCRT). However, it should be investigated whether IMRT could reduce ARE in radical radiotherapy for cervical cancers, considering the inter- and intra-fractional motions of the uterus (5-15 mm) and larger target volume. In Japan, treatment strategy for cervical cancers differs from that of other countries. The intestine is shielded during whole-pelvic irradiation (WPI) and brachytherapy starts earlier. Thus, even in 3DCRT, the ARE incidence can be lower than in other countries. We applied radical IMRT for cervical cancers using tomotherapy and investigated whether the IMRT protocol could reduce ARE and other toxicities. We reviewed patients with cervical cancers treated at 3 institutions that employed the same protocol. In the protocol, patients with UICC 8th stage IB-IVA cervical cancers received radical WPI ± paraaortic irradiation with 45-50.4 Gy delivered at a daily fraction of 1.8 Gy five times a week. Platinum-containing chemotherapy was delivered to ≥ stage III or tumors with ≥ 4 cm in the maximum diameter. After 20-30 Gy of WPI depending on the stage, the rectum, bladder and intestine were shielded and intracavitary brachytherapy (2-4 times at a point A dose of 5-6 Gy) was carried out. In IMRT, a block structure was contoured instead of the center shielding in 3DCRT. The block structure median dose was reduced to ≤ 0.9 Gy/fr. From 2007 to 2011, 3DCRT was used. From 2012, the IMRT protocol was introduced. We compared the IMRT and 3DCRT groups. All patients treated with the protocols were analyzed except patients with: 1) previous history of hysterectomy or radiotherapy and 2) small cell cancer. ARE was defined as the increase in stool of 4–6 times per day over the baseline. In total, 169 patients were treated according to the protocols. Of them, IMRT was delivered to 93 (median age, 63 years) and 3DCRT to 76 (61 years). Chemotherapy was administered to 73 in the IMRT group and 50 in the 3DCRT group (p = 0.08). Lymph node metastases were seen in 44 in the IMRT group and 26 in the 3DCRT group (p = 0.12). The 3-year overall survival and locoregional recurrence rates after IMRT were 84% and 17%, respectively. In the 3DCRT group, these rates were 70% and 20%, respectively. No difference was seen between the 2 groups (p > 0.2). ARE occurred less frequently in the IMRT group than in the 3DCRT group (17/93 vs 24/76, p < 0.05). Grade 3 toxicities were observed in 5 in the IMRT group (rectal bleeding 2, sigmoid colon stenosis 1, bladder tamponade 2) and in 3 in the 3DCRT group (rectal bleeding 1, small intestinal perforation 2) (p = 0.73). There was no ≥ grade 4 toxicity in both groups. Even in the Japanese treatment strategy for cervical cancers, use of IMRT may reduce ARE with similar treatment efficacy.

Impact of Total Radiation Dose on the Treatment Outcomes in Radiotherapy and Concomitant Superselective Intra-arterial High Dose Cisplatin for Locally Advanced Maxillary Sinus Cancer

The purpose of this study is to analyze the relationship between the total radiation dose and the treatment outcomes in radiotherapy and concomitant superselective intra-arterial high dose cisplatin (RADPLAT) for locally advanced maxillary sinus cancer. We have evaluated 54 patients with locally advanced maxillary sinus cancer, who were treated with RADPLAT from March 2004 to February 2019. There were 45 males and 9 females. The median age was 68 years (range 38 to 87 years). T stage was T2 in 2 case, T3 in 10 cases, T4a in 31 cases, and T4b in 11 cases. All patients had no nodal involvement. There were 53 patients who had squamous cell carcinomas, and one with undifferentiated carcinoma. Thirty-four patients received three-dimensional conformal radiotherapy (3DCRT) until 2015, and 20 patients received intensity modulated radiotherapy (IMRT) using volumetric modulated arc therapy since 2016. Median prescribed dose to the local lesion was 66 Gy (range 50 to 66 Gy) in 3DCRT group and 66 Gy (range 60 to 70 Gy) in IMRT group. All patients were irradiated at 2 Gy/fraction. All patients did not receive either prophylactic neck irradiation or volume reduction surgery before RADPLAT. Superselective intra-arterial infusions of high-dose cisplatin (100-120 mg/m2) was performed with median 6 cycles per week (range 1 to 10 cycles) in combination with simultaneous intra-venous infusions of sodium thiosulfate to neutralize cisplatin toxicity. Superselective intra-arterial infusions were performed during or before radiotherapy in all patients. The median follow-up period was 30.3 months (range 2.9 to 193 months). The 3-year local control rate and overall survival rate in all patients were 70.7%, and 86.2%, respectively. The 3-year local control rate were 88.5% in IMRT group, which had a slightly better control rate than 3DCRT group (64.0%) (p = 0.149). However, the patients who were treated with 70 Gy of IMRT (n = 14) tended to have excellent local control rate (91.7%) than patients treated with 66 Gy of IMRT or 3DCRT (72.1%, n = 27) and 60 Gy or lower of 3DCRT (49.2%, n = 13). There was no difference in total dose of cisplatin between the three groups. The 3-year overall survival rate was 100 % in patients treated 70 Gy, 90.0% in patients with 66 Gy, and 82.0% in patients with 60 Gy or lower (p = 0.655). There were no treatment-related deaths. Acute grade 3 mucositis developed in 5 patients in IMRT group and 9 patients in 3DCRT group. No late grade 3 or higher eye disorders except for cataract developed in IMRT group, while blindness occurred in 4 patients in 3DCRT group. The patients who had received 70 Gy using IMRT showed excellent local control rate without increasing adverse events. The total dose may have an impact on local control rate and survival rate in radiotherapy with concomitant superselective intra-arterial high dose cisplatin.

Volumetric Modulated Arc Therapy Versus Three-Dimensional Conformal Radiotherapy for Breast Cancer Patients Treated with Regional Nodal Irradiation

Locally advanced breast cancer is often treated with adjuvant radiotherapy to the chest wall or breast and the regional nodes following surgery. Intensity-modulated radiotherapy (IMRT) can improve target coverage and spare organ at risk, but the efficacy and safety of IMRT for locally advanced breast cancer have not been clarified. We aimed to compare the dosimetric parameters and clinical outcomes between 3D-CRT and volumetric modulated arc therapy (VMAT) for breast cancer. The hypothesis is that VMAT has better target coverage without increasing toxicities. Breast cancer patients who received adjuvant radiotherapy with regional nodes irradiation between July 2016 and December 2019 were included. Patients with a right-sided disease were treated with three-dimensional conformal radiotherapy (3D-CRT), whereas patients with a left-sided disease were treated with VMAT to reduce heart dose. Patients who received bilateral radiotherapy were excluded. Radiotherapy was delivered to the chest wall or breast, and supraclavicular region with or without internal mammary nodes. A dose of 50 Gy in 25 fractions was prescribed to the reference point for 3D-CRT, and to cover 75% of the PTV for VMAT. Single full or two partial arcs with 6MV were used for VMAT. Clinical outcome and dosimetric data were collected retrospectively from medical records. Toxicities were assessed by CTCAE ver.4.0. A total of 74 consecutive patients were included in this study. Thirty-five left-sided breast cancer patients received VMAT, and 39 right-sided breast cancer patients received 3D-CRT. The median follow-up was 591 days. The median age was 50 years. Grade 2 or higher acute dermatitis were observed in 10 patients (29%) with VMAT versus 17 patients (44%) with 3D-CRT (P = 0.18). Grade 3 acute dermatitis occurred in one patient in the 3D-CRT group. Grade 2 radiation pneumonitis occurred in one patient in each group (P = 1.0). Acute radiation esophagitis occurred in 25 patients only in the VMAT group. CTV coverage (CTV V47.5Gy, D95%, D75%) was significantly better for VMAT (86%, 42 Gy, 49 Gy) compared to 3D-CRT (72%, 29 Gy, 46 Gy) (all P < 0.01). Total lung V20 Gy was lower for VMAT versus 3D-CRT (11Gy versus 13 Gy, P < 0.01), whereas total lung V5 Gy and mean dose were higher for VMAT (34 Gy and 7.8 Gy) compared to 3D-CRT (22 Gy and 6.9 Gy) (P < 0.01, 0.01). Because of the laterality, the dose to the heart and esophagus was higher in the VMAT group (P < 0.01, 0.01). Five patients experienced recurrence (two distant metastases in the VMAT group and two distant and one local and distant metastases in the 3D-CRT group). VMAT for breast radiotherapy with regional nodal irradiation had better target coverage and lower lung V20 Gy at the expense of a small increase in the lung mean dose and V5 Gy. VMAT can be safely administered with similar toxicity to 3D-CRT.

Patient-Reported Outcomes in Prospective Cohort of Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer Undergoing Radiotherapy

Among patients with pancreatic cancer, radiotherapy has a role in offering patients local and overall control but data on patient reported outcomes remains scarce. We sought to quantify the patient reported outcomes (PROs) of pancreatic cancer patients receiving radiotherapy (RT) in order to improve patient-physician communication and shared decision making. As part of an IRB-approved study, we prospectively collected PRO data for 57 patients (28 male, 29 female, median age of 68 years [range, 41-83]) with non-metastatic pancreatic cancer who were treated with neoadjuvant chemotherapy (50% FOLFIRINOX, 42% gemcitabine and nab-paclitaxel, 8% other) and RT. Patients received stereotactic body radiation therapy (SBRT) (median dose: 36Gy, 5 fractions for all, n = 13), volumetric modulated arc therapy (VMAT) (median dose: 50.4Gy, 10-28 fractions, n = 20), intensity-modulated radiation therapy (IMRT) (median dose: 62Gy, 10-28 fractions, n = 13), or 3-dimensional conformal radiation treatment (3D-CRT) (median dose: 30Gy, 10-28 fractions, n = 13). All patients were seen by a multidisciplinary care team. PROs were collected using the validated MD Anderson Symptom Inventory for gastrointestinal cancer (MDASI-GI) questionnaire before the start of RT and after completion of RT. We used descriptive statistics to summarize the patients’ characteristics and MDASI-GI scores. We then performed subgroup analyses on the different radiation modalities and used the paired t-test to compare mean between pre-, and post-RT MDASI-GI scores. Median follow up time was 14.0 months and median overall survival was 24.4 months. No significant differences between pre-, and post-RT were found for the composite MDASI-GI score (mean difference: 0.04, 95% CI [-0.23 – 0.32], p = 0.76). Furthermore, there was no significant differences between pre-, and post- therapy for each radiation modality used. The 5 most-severe MDASI-GI items were fatigue, mouth dryness, numbness, taste disturbance, and decreased appetite. Compared to baseline, no increase in the proportion of patients reporting moderate to severe MDASI-GI items was noted in the IMRT group. In the 3D-CRT group, there was no increase in the proportion of patients reporting moderate to severe MDASI-GI items except for appetite (10% increase). Similarly, no change was noted in the SBRT and VMAT groups except for numbness (16% increase) and mouth dryness (8% increase) respectively. Different RT modalities do not seem to affect PROs in a clinically significant way for patients with pancreatic cancer. This may be related to modern medical management and newer radiation technologies. Future studies will investigate additional time points and correlate PRO data with outcomes.

Transitioning from conformal radiotherapy to intensity-modulated radiotherapy after radical prostatectomy: Clinical benefit, oncologic outcomes and incidence of gastrointestinal and urinary toxicities.

The purpose of this study was to review genitourinary (GU) and gastrointestinal (GI) toxicity associated with high-dose radiotherapy (RT) delivered with 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) or volumetric arc therapy (VMAT) following radical prostatectomy (RP). RP is a therapeutic option for the management of prostate cancer (PrCa). When assessing postoperative RT techniques for PrCa, the published literature focuses on patients treated with 2-dimensional conventional methods without reflecting the implementation of 3D-CRT, IMRT, or VMAT. A total of 83 patients were included in this analysis; 30 patients received 3D-CRT, and 53 patients received IMRT/VMAT. Acute and late symptoms of the GU and lower GI tract were retrospectively graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer radiation toxicity grading systems. The relapse failure-free rate and overall survival were also evaluated. The rate of acute GU toxicity was 9.4% vs. 13.3% for the IMRT/VMAT and 3D-CRT groups (p = 0.583). The 5-year actuarial rates of late GI toxicity for IMRT/VMAT and 3D-CRT treatments were 1.9% and 6.7%, respectively. The rate of late GU toxicity for the IMRT/VMAT and 3D-CRT treatment groups was 7.5% and 16.6%, respectively (p = 0.199). We found no association between acute or late toxicity and the RT technique in univariate and multivariate analyses. Postprostatectomy IMRT/VMAT and 3D-CRT achieved similar morbidity and cancer control outcomes. The clinical benefit of highly conformal techniques in this setting is unclear although formal analysis is needed.

Comparison between Intensity-Modulated Radiotherapy and Three-Dimensional Conformal Radiotherapy for Their Effectiveness in Esophageal Cancer Treatment: A Retrospective Single Institution Study

Although a large number of influential studies that have been conducted worldwide on locally advanced esophageal cancer (EC) have employed the treatment modality of three-dimensional conformal radiotherapy (3D-CRT), an advanced as well as highly conformal technology known as intensity-modulated radiotherapy (IMRT) has attracted increasing attention from the radiotherapy research community. This is because of the clear advantages of IMRT, including decrease in radiation dose that reaches critical cardiopulmonary organs. These two treatment modalities need to be investigated with regard to their effect on local control rate and patient survival. In addition, related clinical factors also need to be explored. Data from a total of 431 patients with locally advanced EC, who underwent radiation therapy between January 1, 2010 and December 31, 2013, were included in the present study. Two hundred and ninety-three patients received 3D-CRT, while 138 patients received IMRT. We constructed propensity score matches to make the two groups be comparable (136 patients in 3D-CRT group and 138 patients in IMRT group. Kaplan–Meier analysis was conducted to evaluate the endpoint of overall survival (OS). A Cox proportional hazards model was employed to analyze the relationship between the associated factors and the outcomes via univariate and multivariate approaches. The mean follow-up period was 36.2 months, and the median follow-up period was 23 months. For the IMRT group, the median OS was 31 months, and the 1-, 3-, and 5-year OS rates were 70.3%, 50.0%, and 42.8%, respectively, while for the 3D-CRT group, the median OS was 22 months, and the 1-, 3-, and 5-year OS rates were 63.2%, 41.0%, and 35.4%, respectively (p < 0.05). The univariate analysis revealed that quit drinking, chemotherapy, and concurrent chemotherapy were significant risk factors for the prognosis of EC (p < 0.05), as well as the radiation therapy technique used (p=0.052). The multivariate analysis indicated that chemotherapy and quit drinking were independent predictive factors for OS. OS is found to be significantly better in the IMRT group, compared with that of the 3D-CRT group. Even though these outcomes need further validation, IMRT should be considered preferentially as a therapeutic option for EC, in combination with chemotherapy and persuading patients to quit drinking.

A prospective, comparative analysis of acute toxicity profile between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in locally advanced head and neck cancer patients

IntroductionThe advances of modern radiotherapy have emerged with the development of conformal radiotherapy techniques, such as the three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). We prospectively compared acute toxicities and treatment-compliance between IMRT and 3DCRT in patients with locally advanced head and neck carcinoma. Method80 patients were enrolled in this comparative prospective non-randomized study. Inclusion criteria were patients with locally advanced carcinoma of hypopharynx, oropharynx and larynx. 40 patients were treated with IMRT and 40 patients with 3DCRT to dose of 70 Gy in 35 fractions, along with concurrent cisplatin weekly chemotherapy. All patients were assessed weekly during chemoradiotherapy treatment and after 3 months of the treatment. Results15 patients (38.4%) versus 8 patients (20.51%) developed grade 3 mucositis in the 3DCRT and IMRT group respectively (p= <0.001). At three months post chemo-radiotherapy treatment, 17 patients (43.6%) versus 7 patients (17.9%) had grade 2 dysphagia in 3DCRT and IMRT group respectively (p = 0.029). At three months post radiotherapy, grade 3 xerostomia was seen in 3 patients (7.6%) in 3DCRT group versus no patient (0%) in IMRT group (p = 0.006). IMRT group had lower incidence of grade 3 dermatitis (p = 0.043), weight loss of the patients during the treatment (p = 0.126), lesser requirement of nasogastric intubation (p = 0.003) and better treatment-compliance (p = 0.336) compared to 3DCRT. ConclusionIMRT reduced the incidence of severe mucositis, dysphagia, xerostomia, weight-loss of the patients, requirements for nasogastric tube and it improved the treatment-compliance compared to 3DCRT in locally advanced head neck cancer patients treated by chemo-radiotherapy.

Intensity-modulated radiotherapy for stage I glottic cancer: a short-term outcomes compared with three-dimensional conformal radiotherapy.

PurposeTo investigate the differences in treatment outcomes between two radiation techniques, intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT).Materials and MethodsWe retrospectively analyzed 160 (IMRT = 23, 3DCRT = 137) patients with stage I glottic cancer treated from January 2005 through December 2016. The IMRT was performed with TomoTherapy (16 patients), volumetric-modulated arc therapy (6 patients), and step-and-shoot technique (1 patient), respectively. The 3DCRT was performed with bilateral parallel opposing fields. The median follow-up duration was 30 months (range, 31 to 42 months) in the IMRT group and 65 months (range, 20 to 143 months) in the 3DCRT group.ResultsThe 5-year overall survival and 3-year local control rates of the 160 patients were 95.7% and 91.4%, respectively. There was no significant difference in 3-year local control rates between the IMRT and 3DCRT groups (94.4% vs. 91.0%; p = 0.587). Thirteen of 137 patients in the 3DCRT group had recurrences. In the IMRT group, one patient had a recurrence at the true vocal cord. Patients treated with IMRT had less grade 2 skin reaction than the 3DCRT group, but this had no statistical significance (4.3% vs. 21.2%; p = 0.080).ConclusionIMRT had comparable outcomes with 3DCRT, and a trend of less acute skin reaction in stage I glottic cancer patients

IMRT Reduces Acute Toxicity in Patients Treated With Preoperative Chemoradiation for Gastric Cancer

PurposePreoperative chemoradiation is being currently evaluated in 2 randomized international trials. However, chemoradiation for gastric cancer can be associated with relatively high rates of acute toxicity. We compared rates of toxicity, toxicity-related events, and oncologic outcomes in patients treated with intensity modulated radiation therapy (IMRT) and those treated with 3-dimensional conformal radiation therapy (3DCRT). Methods and MaterialsWe retrospectively reviewed records of 202 patients with consecutive gastric cancer treated with preoperative intent radiation therapy at our institution from 1998 to 2018. Patients with gastroesophageal junction involvement and those with metastatic disease were excluded. Eighty-two patients received 3DCRT, and 120 patients received IMRT. The median radiation dose was 45 Gy, and 99% received concurrent chemotherapy. ResultsThere were no significant differences between the 3DCRT and IMRT groups regarding sex, race, histology, tumor location, histology, or nodal stage. The rate of grade 3 to 4 acute toxicity was significantly lower in patients treated with IMRT compared with 3DCRT (49% vs 70%, P = .004). The composite rate of toxicity-related events (hospitalization, feeding tube use, intravenous rehydration, or radiation therapy breaks) was also significantly lower in patients treated with IMRT compared with 3DCRT (56% vs 85%, P <.001). In addition, 68% of patients who received IMRT and 73% of patients who received 3DCRT underwent subsequent surgical resection (P = .245). Among patients who underwent surgery, the 3-year overall survival rates were not significantly different between those treated with IMRT and 3DCRT (71% vs 69%, P = .786). Patients receiving IMRT had a significantly higher absolute nadir lymphocyte count compared with patients receiving 3DCRT (median, 0.21 vs 0.16 K/UL; P = .047). ConclusionsOur study suggests that IMRT might significantly reduce rates of grade 3 to 4 acute toxicity and toxicity-related events compared with 3DCRT, with no significant difference in oncologic outcomes. IMRT is an appropriate and possibly preferable radiation modality in patients treated with preoperative chemoradiation for gastric cancer.

Efficacy of combined modality therapy with sorafenib following hepatic arterial injection chemotherapy and three-dimensional conformal radiotherapy for advanced hepatocellular carcinoma with major vascular invasion.

The prognosis of hepatocellular carcinoma (HCC) patients exhibiting macroscopic vascular invasion (MVI) is poor, and the most appropriate treatment approach remains unclear. The current study aimed to investigate the efficacy and safety of sorafenib treatment following chemoradiotherapy for advanced HCC exhibiting MVI. A newly reported regimen, including 5-fluorouracil and cisplatin therapy (NewFP), plus three-dimensional conformal radiotherapy (3D-CRT) for MVI was used as the initial treatment. Additionally, sorafenib, as a secondary treatment, was administered after NewFP plus 3D-CRT for MVI. The present retrospective study enrolled patients with unresectable advanced HCC that was treated with NewFP plus 3D-CRT for MVI between January 2009 and December 2017. In total, 32 HCC patients with MVI were registered. Of these 32 patients, 18 were treated with NewFP plus 3D-CRT for MVI (NewFP + 3D-CRT group) and 14 were treated with sorafenib following NewFP plus 3D-CRT for MVI (sorafenib after NewFP + 3D-CRT group). The study endpoints were overall survival, overall response rate and disease control rate. Clinical factors influencing overall survival were identified using univariate and multivariate analyses. The median survival time in the NewFP + 3D-CRT group and sorafenib following NewFP + 3D-CRT group was 6.7 and 49.2 months, respectively (P=0.0003). For patients with advanced HCC exhibiting MVI, the initial treatment with NewFP plus 3D-CRT for MVI was well tolerated. The administration of sorafenib as the secondary treatment following NewFP plus 3D-CRT for MVI was associated with a significantly higher overall response rate, disease control rate and increased overall survival as compared with the NewFP plus 3D-CRT treatment.

IMRT Reduces Acute Toxicity in Patients Treated with Preoperative Chemoradiation for Gastric Cancer

Two large randomized trials are currently investigating preoperative chemoradiation for localized gastric adenocarcinoma. However, radiation therapy (RT) can be associated with relatively high rates of acute toxicity. Newer techniques, such as intensity modulated RT (IMRT), could reduce toxicity by reducing radiation dose to normal structures. Our goal was to compare rates of toxicity, toxicity-related events, and oncologic outcomes in patients treated with IMRT compared to 3D conformal RT (3DCRT). The records of 202 gastric cancer patients treated with preoperative intent RT at our institution from 1998-2018 were retrospectively reviewed. Demographic data, treatment details, acute and late toxicities (CTCAE 4.0), progression and survival data were recorded. Patients who had stage IV disease were excluded. Statistical analysis included descriptive statistics, Cox regression analysis, and Kaplan-Meier survival. 54% were male, and the median age was 63. 82 patients received 3DCRT and 120 patients received IMRT. The median radiation dose was 45Gy (IQR: 45-45 Gy). 78% of patients in the 3DCRT group and 95% of patients in the IMRT group received neoadjuvant chemotherapy prior to RT (p=0.001). 99% of patients in both groups received concurrent chemotherapy. There were no significant differences between the 3DCRT and IMRT groups with respect to gender, race, histology, tumor, or nodal stage. The rate of grade 3-4 acute toxicity was significantly lower in patients treated with IMRT compared to those treated with 3DCRT (53% vs. 73%, p=0.004). The composite rate of toxicity-related events (hospitalization, feeding tube, IV rehydration or RT breaks) was also significantly lower in patients treated with IMRT compared to 3DCRT (56% vs. 85%, p<0.001). 73% of patients who received 3DCRT and 68% of patients who received IMRT underwent subsequent surgical resection (p=0.245). Among patients who underwent surgical resection, there was no significant difference in the rate of positive margins between those who received 3DCRT and those who received IMRT (7% vs 15%, p=0.13). Among patients who underwent surgical resection, the 3-year OS and PFS rates were not significantly different in patients receiving 3DCRT compared to IMRT (OS 73% vs. 73%, p=0.93, PFS 65% vs. 64%, p=0.68). Among patients who did not undergo surgical resection, the 3-year OS and PFS rates were also not significantly different in patients receiving 3DCRT compared to IMRT (OS 27% vs. 28%, p=0.93; PFS 19% vs. 14%, p=0.69). Our study indicates a reduction in the rates of grade 3-4 acute toxicity and toxicity-associated events in patients treated with IMRT compared to 3DCRT, with no significant difference in oncologic outcomes. These findings suggest that IMRT should be considered as the preferred radiation modality in patients treated with preoperative chemoradiation for gastric cancer.