IMRT Group Research Articles

Lymphopenia Induced by Different Neoadjuvant Chemo-Radiotherapy Schedules in Patients with Rectal Cancer: Bone Marrow as an Organ at Risk.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008

Background and purposeHypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. Materials and methodsIn 2012–2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. ResultsThe analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3–9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632–36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001–0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999–1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. ConclusionThe study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Comparison of radiotherapy techniques in patients with thymic epithelial tumor who underwent postoperative radiotherapy.

This retrospective study aimed to compare clinical outcomes and dosimetric parameters between radiation therapy (RT) techniques in patients with thymic epithelial tumor (TET). From January 2016 to December 2020, 101 patients with TET received adjuvant RT (median, 52.8 Gy; range, 48.4 to 66.0). Three different RT techniques were compared: three-dimensional conformal RT (3D-CRT; n = 59, 58.4%), intensity-modulated RT (IMRT; n = 23, 22.8%), and proton beam therapy (PBT; n = 19, 18.8%). The median age of the patients and the follow-up period were 55 years (range, 28 to 79) and 43.4 months (range, 7.7 to 77.2). Patients in the PBT group were of the youngest age (mean age, 45.4 years), while those in IMRT group had the largest clinical target volume (mean volume, 149.6 mL). Patients in the PBT group had a lower mean lung dose (4.4 Gy vs. 7.6 Gy vs. 10.9 Gy, respectively; p < 0.001), lower mean heart dose (5.4 Gy vs. 10.0 Gy vs. 13.1 Gy, respectively; p = 0.003), and lower mean esophageal dose than patients in the 3D-CRT and IMRT groups (6.3 Gy vs. 9.8 Gy vs. 13.5 Gy, respectively; p = 0.011). Twenty patients (19.8%) showed disease recurrence, and seven patients (6.9%) died. The differences in the survival rates between RT groups were not statistically significant. In patients with TET who underwent adjuvant RT, PBT resulted in a lower dose of exposure to adjacent organs at risk. Survival outcomes for patients in PBT group were not significantly different from those in other groups.

Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy

Background and purposeConcurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. Materials and methodsProspectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients. Results271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0–4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9–12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16–0.79, P = 0.01). ConclusionIMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.

Evaluating the Effects of Bone Marrow Sparing Radiotherapy on Acute Hematologic Toxicity for Patients with Locoregionally Advanced Cervical Cancer: A Prospective Phase II Randomized Controlled Trial

Bone marrow sparing intensity modulated radiotherapy (BMS-IMRT) can reduce the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients receiving concurrent chemoradiotherapy (CCRT), but the norm has been controversial. The purpose of the study was to evaluate the effects of bone marrow (BM) V40 <25% on decreasing the incidence of acute HT in a prospective clinical trial. A total of 242 LACC patients were recruited from May 2021 to May 2022, who were evenly randomized into BMS-IMRT group and standard IMRT group according to a computer-generated random number list. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. For patients in BMS-IMRT group, the outer contour of pelvic bone, lumbar spine and left and right femur heads were additionally delineated as a surrogate for BM, and V40 <25% was prescribed. Blood counts were tested weekly, of which nadirs during external beam radiotherapy (EBRT) were graded to assess acute HT as primary observation index. Second observation index were dosimetric parameters of EBRT plan from the dose volume histograms (DVHs). Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. Baseline demographic, disease and treatment characteristics were all balanced between BMS-IMRT group and standard IMRT group. BMS-IMRT was associated with a lower incidence of grade ≥2 and grade ≥3 acute HT, leukopenia and neutropenia (72.70% vs 90.90%, P <0.001*; 16.50% vs 65.30%, P <0.001*; 66.10% vs 85.10%, P = 0.001*; 13.20% vs 54.50%, P <0.001*; 37.20% vs 66.10%, P <0.001*; 10.70% vs 43.80%, P <0.001*). Plan target volume (PTV) for all patients satisfied the clinical requirement of V(100%) ≥95%, and conformity and homogeneity were both comparable between 2 groups. BMS also decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femur head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P <0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. BM V40 <25% can reduce the risks of acute HT for LACC patients receiving CCRT while the dose delivery of target volume and other normal tissues were not compromised. With great practicality and applicability, BM V40 <25% is a promising strategy, making BMS-IMRT widespread especially in the area where application of image guided radiotherapy (IGRT) such as 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET)/CT is not popularized. Chinese clinical trial registry (ChiCTR2200066485).

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial

Most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on quality of life. We aimed to investigate if dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) reduced radiation dose to the dysphagia and aspiration related structures and improved swallowing function compared with standard IMRT. DARS was a parallel-group, phase 3, multicentre, randomised, controlled trial done in 22 radiotherapy centres in Ireland and the UK. Participants were aged 18 years and older, had T1-4, N0-3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. Participants were centrally randomly assigned (1:1) using a minimisation algorithm (balancing factors: centre, chemotherapy use, tumour type, American Joint Committee on Cancer tumour stage) to receive DO-IMRT or standard IMRT. Participants and speech language therapists were masked to treatment allocation. Radiotherapy was given in 30 fractions over 6 weeks. Dose was 65 Gy to primary and nodal tumour and 54 Gy to remaining pharyngeal subsite and nodal areas at risk of microscopic disease. For DO-IMRT, the volume of the superior and middle pharyngeal constrictor muscle or inferior pharyngeal constrictor muscle lying outside the high-dose target volume had a mandatory 50 Gy mean dose constraint. The primary endpoint was MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after radiotherapy, analysed in the modified intention-to-treat population that included only patients who completed a 12-month assessment; safety was assessed in all randomly assigned patients who received at least one fraction of radiotherapy. The study is registered with the ISRCTN registry, ISRCTN25458988, and is complete. From June 24, 2016, to April 27, 2018, 118 patients were registered, 112 of whom were randomly assigned (56 to each treatment group). 22 (20%) participants were female and 90 (80%) were male; median age was 57 years (IQR 52-62). Median follow-up was 39·5 months (IQR 37·8-50·0). Patients in the DO-IMRT group had significantly higher MDADI composite scores at 12 months than patients in the standard IMRT group (mean score 77·7 [SD 16·1] vs 70·6 [17·3]; mean difference 7·2 [95% CI 0·4-13·9]; p=0·037). 25 serious adverse events (16 serious adverse events assessed as unrelated to study treatment [nine in the DO-IMRT group and seven in the standard IMRT group] and nine serious adverse reactions [two vs seven]) were reported in 23 patients. The most common grade 3-4 late adverse events were hearing impairment (nine [16%] of 55 in the DO-IMRT group vs seven [13%] of 55 in the standard IMRT group), dry mouth (three [5%] vs eight [15%]), and dysphagia (three [5%] vs eight [15%]). There were no treatment-related deaths. Our findings suggest that DO-IMRT improves patient-reported swallowing function compared with standard IMRT. DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers. Cancer Research UK.

Yoğunluk Ayarlı veya 3 Boyutlu Konformal Radyasyon Tedavisi Kullanılarak Definitif Kemoradyoterapi İle Tedavi Edilen Servikal Özofagus Kanserinin Sağkalım Sonuçları: Tek Merkez Deneyimi

Abstract&#x0D; Objective: The aim of this study is to report the survival and treatment results of patients with cervical esophageal cancer treated with definitive chemoradiotherapy, whose incidence is very low in the population and there is not enough information about treatment and toxicity results in the literature. &#x0D; Material and Method: Between 2013 and 2022, 10 patients (six males and four females) with cervical esophageal cancer treated with definitive chemoradiotherapy were included. Among these patients, seven had stage II disease, one stage III, and 2 stage IVA. All patients received radiotherapy at a median dose of 50.4 Gy and concurrent weekly chemotherapy.&#x0D; Results: The median follow-up period was 18 months. The two-year and 5-year overall survival rates were 42.2% and 21.1%, respectively. The two-year and 5-year disease-free survival rates were 45.7% and 22.9%, respectively. Disease progression was noted in 3 out of 10 patients (30%). Three patients were still alive during analyze. Percutaneous enteral gastrostomy was performed in 3 of 10 patients. These requirement occured in 1 due to local progression, and in the remaining 2 patients due to the side effect of RT. &#x0D; Conclusions: Overall survival rates were low, as similar findings appear in the literature. It was remarkable that the need for a percutaneous enteral gastrostomy was not observed in the IMRT group. All patients with complete remission were in stage 2.

Clinical study of acute toxicity of pelvic bone marrow-sparing intensity-modulated radiotherapy for cervical cancer.

To compare the dose volume of the target area and the toxicity of pelvic bone marrow-sparing intensity-modulated radiotherapy (PBMS-IMRT) with routine IMRT in patients undergoing radiochemotherapy for cervical cancer. Forty patients with indications for adjuvant radiochemotherapy after cervical cancer surgery were selected and randomly divided into IMRT (n = 20) and PBMS-IMRT (n = 20) groups to observe and record the toxicity and its severity in the blood, gastrointestinal tract, and genitourinary system. There was no significant difference in the target area conformity index (CI) or homogeneity index (HI) between the two groups (p > 0.05). The pelvic bone V10-V50 in the PBMS-IMRT group were lower than those in the IMRT group (p < 0.05), and there was lower hematological toxicity (p < 0.05) and fewer delays or interruptions in chemotherapy and/or radiotherapy (p < 0.05) in the PBMS-IMRT group. The toxicity to the gastrointestinal and genitourinary systems in the two groups was not significantly different (p > 0.05). PBMS-IMRT significantly reduced the dose volume of the pelvic bone marrow, thereby reducing the incidence of bone marrow suppression. However, it had no significant impact on the gastrointestinal or genitourinary systems.

A Prospective Study of Differences in the Incidence of Radiation Pneumonitis in Elderly Patients between Volumetric Arc Modulated Therapy and Step-and-Shoot Intensity-Modulated Radiation Therapy

<h3>Purpose/Objective(s)</h3> Studies have shown that the incidence of radiation pneumonitis in elderly patients with thoracic tumor radiotherapy is high, and there is a significant correlation with smoking, pulmonary dysfunction, combined chemotherapy, radiation dose and radiation site. VMAT is considered a large-scale low-dose radiation therapy modality, while Step and Shot's IMRT is a small-scale low-dose radiation therapy modality. To test whether these two radiotherapy modalities have different incidences of radiation pneumonitis in elderly lung cancer patients, we conducted this prospective randomized controlled study. <h3>Materials/Methods</h3> A total of 50 elderly patients with non-small cell lung cancer (NSCLC) diagnosed from January 2019 to January 2020 were included and randomly divided into the VMAT group and the IMRT group according to the ratio of 1:1. We collected all irradiated lung volumes from 5 to 75 Gy at the interval of 5 Gy. The occurrence of radiation pneumonitis within six months after treatment was followed up. Fisher's exact test was used to analyze the incidence of radiation pneumonitis between the two groups. In addition, linear regression was used to analyze the fitting situation of radiation pneumonitis in the two groups with an interval of 5 Gy. <h3>Results</h3> The average age was 69 yrs, lung volume was 3310±837 ml, radiation dose was 68.8±8.3 Gy. The I to V levels of radiation pneumonitis were 12, 10, 2, 1, 0 in VMAT and 10, 12, 3, 0,0 in IMRT, respectively, P=0.610 with Fisher`s exact test. Judging from the coefficient of determination (R2) of the fitted model, no matter which grouping, the dose and the inflammatory ratio were linearly correlated and negatively correlated. From the distribution of the scatter plot, the fitting degree of IMRT is higher, and the scatter points are more concentrated on both sides of the curve, while VMAT is more diffuse. The IMRT fitting model is Y=42.19-3.14x, and the VMAT fitting model is Y=36.48-2.91x. The β coefficient (3.14) of the former is greater than that of the latter (2.91), indicating that with the increase of radiation dose, The inflammatory ratio decreased more rapidly. <h3>Conclusion</h3> In this small prospective pilot experiment, we did not directly find a difference in the incidence of radiation pneumonitis between the two radiation therapy modalities. However, in further analysis of the dose distribution in the lungs, we found that the trend of pneumonia incidences in the IMRT group was lower than that in the VMAT group as the dose increased. This study warrants further conduct in elderly patients to demonstrate which radiotherapy modality is more appropriate.

The Impact of an Incidental Dose on Axillary Tumor Control and Toxicity in Localized Breast Cancer: A Retrospective Analysis.

Simple SummaryThe incidental axillary dose varies according to the whole breast irradiation technique. However, this dose has not been shown to be a prognostic factor for locoregional recurrence. The objectives of our retrospective study are to dosimetrically evaluate the incidental axillary dose according to the different irradiation techniques and the risk factors of axillary recurrence. We confirmed that the irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of high tangential beams and the mean dose delivered at level II.Purpose: The dosimetric analysis of the incidental axillary dose delivered to axillary lymph node levels I–III by different techniques of whole breast irradiation and the analysis of prognostic factors of axillary recurrence of breast cancer. Methods: We perform a retrospective analysis that includes 171 patients with localized breast carcinoma irradiated at Centre Paul Strauss. To be included in the study, patients had to have a histological confirmation of breast cancer diagnosis, surgical treatment without axillary lymph node dissection (ALND), whole breast irradiation without axillary irradiation by a specific field, and a treatment plan available. Results: Three patients had lymph node recurrence. There was no significant correlation between the maximal or mean dose delivered at the three axillary levels and the risk of axillary lymph node recurrence. There was no significant correlation between the irradiation technique and the risk of axillary lymph node recurrence. Two patients, both in the HT group, had lymphoedema. There was significantly more lymphoedema in the HT group than in the ST and IMRT groups (p < 0.048). The mean dose in level II was significantly higher in the group of patients with lymphoedema (3.45 Gy (1.08; 9.62) vs. 23.4 Gy (23.1; 23.6)) (p < 0.02). Conclusion: The irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of HT and the mean dose delivered at level II.

Diffusion-Weighted Magnetic Resonance Imaging-Guided Dose Painting in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy: A Randomized, Controlled Clinical Trial

We hypothesized that diffusion-weighted magnetic resonance imaging (DWI)-guided dose-painting intensity modulated radiation therapy (DP-IMRT) is associated with improved local tumor control and survival in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized study was to compare the efficacy and toxicity of DWI-guided DP-IMRT to conventional magnetic resonance imaging (MRI)-based IMRT in locoregional advanced NPC. A total of 260 patients with stage III-IVa NPC disease were randomly assigned in a 1:1 ratio to receive induction chemotherapy followed by chemoradiotherapy by DWI-guided DP-IMRT (group A, n=130) or conventional MRI-based IMRT (group B, n=130) in this prospective clinical trial. In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean) according to MRI before induction chemotherapy. The dose to GTVnx-DWI was escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group B, planning gross tumor volumeof nasopharynx was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR1800015779). A total of 260 patients were included in the trial (130 patients in group A and 130 in group B). Complete response rates after chemoradiotherapy were 99.2% (129 of 130) and 93.8% (122 of 130) in groups A and B, respectively (P=.042). At a median follow-up of 25 months, DWI-guided DP-IMRT was associated with improved 2-year disease-free survival (DFS; 93.6% [95% confidence interval {CI}, 88.1%-99.1%] vs 87.5% [95% CI, 81.4%-93.6%], P=.015), local recurrence-free survival (100% [95% CI, not applicable {NA}] vs 91.3% [95% CI, 85.4%-97.2%]), locoregional recurrence-free survival (LRRFS; 95.8% [95% CI, NA] vs 91.3% [95% CI, 85.4%-97.2%]), distant metastasis-free survival (DMFS; 97.8% [95% CI, NA] vs 90.9% [95% CI, 85.8%-96.0%]), and overall survival (100% [95% CI, NA] vs 94.5% [95% CI, 89.2%-99.8%]). Zero and 3 patients had local-only recurrences in group A and B, respectively. The most common site of first failure in each arm was distant organ failure. No statistically significant differences in acute and late toxic effects were observed. Multivariate analyses showed that DP (DWI-guided DP-IMRT vs conventional MRI-based IMRT without DP) was associated with DFS, local recurrence-free survival, LRRFS, and distant metastasis-free survival. Epstein-Barr virus DNA level was associated with DFS and LRRFS. DWI-guided DP-IMRT plus chemotherapy is associated with a disease-free survival benefit compared with conventional MRI-based IMRT among patients with locoregionally advanced NPC without increasing acute toxic effects.

Hematologic Toxicity Comparison of Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy in Anal Cancer Patients

<h3>Purpose/Objective(s)</h3> IMPT has been shown to decrease the pelvic bone marrow (PBM) dose compared to IMRT in anal cancer dosimetric studies, however it is unknown whether IMPT reduces hematologic toxicity. By converting discrete adverse event (AEs) data into a continuous variable (0-5), the Toxicity Index (TI) is a novel method of accounting for all AEs within a class and multiple events with the same grade (Rogatko et al. Clin Cancer Res 2004). We hypothesize that the hematologic TI (Hem TI) is a feasible method for evaluating all AEs within the hematologic class during chemoradiation for anal cancer and that IMPT results in a decrease in Hem TI compared to IMRT. <h3>Materials/Methods</h3> Patients enrolled on a prospective feasibility trial assessing the use of IMPT for anal cancer were compared to contemporaneous patients treated with IMRT. All patients received concurrent chemotherapy (83% 5-Fluorouracil/Mitomycin C). Radiation dose was prescribed according to RTOG 0529 in both groups. All hematologic events (CTCAE version 5.0 anemia, lymphopenia, thrombocytopenia, neutropenia, and leukopenia) during treatment were used to calculate the Hem TI for each patient. PBM was defined as all bone from L5/S1 interspace through the ischial tuberosity including the bilateral femoral heads. Demographics, PBM dosimetric parameters, and the Hem TI were compared between groups using the Wilcoxon rank-sum test and Fisher's exact test. A multivariable, probabilistic index model (PIM) was used to evaluate predictors of Hem TI in the setting of demographic and treatment (IMPT vs IMRT) variables. <h3>Results</h3> Forty-eight patients treated with definitive chemoradiation for anal cancer between 2015 and 2021 at a single institution were included in this analysis (IMRT = 34, IMPT = 14). Table 1 displays demographic, hematologic toxicity and PBM dose comparisons between the IMRT and IMPT groups. The Hem TI was not decreased in patients receiving IMPT despite reduction in all PBM metrics. Based on the PIM model, the probability that a randomly selected patient in the IMPT group has a higher Hem TI compared to a similar patient in the IMRT group is 82% (<i>P</i> < 0.05). <h3>Conclusion</h3> Hem TI is a feasible method for reporting the totality of hematologic events in anal cancer treatment. IMPT patients had lower PBM dose metrics but this was not associated with lower hematologic toxicity when compared to IMRT. Preferential treatment of the active bone marrow-rich lumbosacral space with standard PA fields used during IMPT will be evaluated further as a potential explanation of these findings.

Quality of Life After Simultaneously Integrated Boost With Intensity-Modulated vs. Conventional Radiotherapy Followed by Sequential Boost for Adjuvant Treatment of Breast Cancer: 2-Year Results of the Multicenter Randomized IMRT-MC2 Trial

We recently published 2-year results of the prospective, randomized IMRT-MC2 trial, showing non-inferior local control and cosmesis in breast cancer patients after conventionally fractionated intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB), compared to 3D-conformal radiotherapy with sequential boost (3D-CRT-seqB). The present study reports on 2-year quality of life results.Five hundred two patients were enrolled to analyze non-inferiority of IMRT-SIB (50.4 Gy in 1.8 Gy fractions with a 64.4 Gy SIB to the tumor bed in 2.3 Gy fractions) to 3D-CRT-seqB (50.4 Gy in 1.8 Gy fractions, followed by a sequential boost of 16 Gy in 2 Gy fractions). For quality of life (QoL) assessment, patients completed the QLQ-C30 (15 items) and QLQ-BR23 (8 items) questionnaires at baseline and 6 weeks and 2 years after radiotherapy. Comparisons between treatment groups were made at 6 weeks and 2 years after radiotherapy, using Mann-Whitney U-test. The Friedmann test was used to compare QoL at different time points during follow-up (baseline, 6 weeks and 2 years after radiotherapy) and to detect significant changes of QoL over all time points.After six weeks and two years, 237 and 212 QoL questionnaires (94 % and 84 %) were available in the IMRT group, 231 and 210 (93 % and 84 %) in the control group, respectively. The only significant difference of QoL scores between the IMRT-SIB and the 3-D-CRT-seqB group was seen 6 weeks after radiotherapy for pain (22.3 points for IMRT vs. 27.0 points for 3D-CRT-seqB; P = 0.033; r = 0.102) and for arm symptoms (18.1 points for IMRT vs. 23.6 points for 3D-CRT-seqB; P = 0.013; r = 0.118), both favoring IMRT. Looking at changes after two years compared to baseline, both arms showed significant improvement in global score (IMRT: P = 0.009, r = 0.021; 3D-CRT: P = 0.001, r = 0.028) with slight deterioration on the role (IMRT: P = 0.008, r = 0.021; 3-D-CRT: P = 0.001, r = 0.038) and social functioning (IMRT: P = 0.013, r = 0.021; 3D-CRT: P = 0.001, r = 0.033) as well as the future perspectives scale (IMRT: P = 0.003, r = 0.026; 3D-CRT: P = 0.0034, r = 0.020).This is the first randomized phase III trial demonstrating that simultaneously integrated boost irradiation was associated with slightly superior quality of life compared to conventional sequential boost irradiation. These findings further support the widely clinical implementation of SIB in adjuvant breast cancer treatment. NCT01322854.

Acute Toxicity Following Ipsilateral Head and Neck Radiation Therapy: Proton vs. Intensity-Modulated Photon Radiotherapy

Given its unique properties, proton beam radiation therapy has the ability to reduce dose to at-risk organs. Proton's Bragg peak gives sharp distal dose fall off, which results in little or no dose beyond this region. As such, ipsilateral head and neck radiation with protons can spare the contralateral side to a greater extent than photon-based radiation, potentially causing reduced acute toxicity.Eighty-six patients (59 protons and 27 intensity modulated radiation therapy [IMRT]) who received primary or adjuvant ipsilateral head and neck radiation were retrospectively reviewed. Patients received radiation to one side and this must have included at least the parotid region in the treatment field. Primary disease site was major salivary gland in 40, cutaneous in 23, tonsil in 19 and other in 4 patients. Passive scatter proton therapy was delivered with 1-3 fields daily. Median dose delivered was 66 cobalt gray equivalent with protons and 60 gray with IMRT.No grade 4 or greater acute mucositis was present in either group. Median acute mucositis was grade 1 for protons and 2 for IMRT. Grade 0, 1, 2 or 3 acute mucositis toxicity was present in 28 (47%), 11 (19%), 17 (29%) and 3 patients (5%) respectively with proton treatment and present in 7 (26%), 3 (11%), 12 (44%) and 5 patients (19%) respectively with IMRT (P = 0.053). Percutaneous endoscopic gastrostomy (PEG) tube was placed during radiation treatment for 1 patient (2%) with protons and 4 patients (15%) for IMRT (P = 0.032). Two patients in the proton group had a PEG tube placed prior to starting radiation and one patient in the IMRT group refused PEG tube placement despite treating physician recommendation. No grade 4 or greater acute radiation dermatitis was experienced by patients in either group. Median acute radiation dermatitis was grade 2 for protons and 2 for IMRT. Grade 0, 1, 2 or 3 toxicity was present in 0 (0%), 7 (12%), 47 (80%) and 4 patients (7%) respectively with proton treatment and present in 0 (0%), 5 (19%), 20 (74%) and 2 patients (7%) respectively with IMRT (P = 0.718). The majority of patients in both treatment groups completed treatment with ≤ 5 days of missed fractions (86.4% with protons, 85.1% with IMRT). Median number of missed treatment days was 2 in both groups.Ipsilateral radiation therapy is well tolerated with IMRT and proton based radiation therapy. Fewer patients underwent PEG tube placement in the proton cohort, however these results should be further validated with prospective patient-toxicity centered studies.

Positron Emission Tomography-Guided Bone Marrow-Sparing Radiation Therapy for Locoregionally Advanced Cervix Cancer: Final Results From the INTERTECC Phase II/III Trial

PurposeTo test effects of positron emission tomography (PET)–based bone marrow–sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. Methods and MaterialsIn an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS. ResultsIn total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P = .048) and in the combined cohort (13% vs 35%, χ2P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group. ConclusionsPET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

Effect of Pelvic Bone Marrow Sparing Intensity Modulated Radiation Therapy on Acute Hematologic Toxicity in Rectal Cancer Patients Undergoing Chemo-Radiotherapy.

BackgroundWhile chemo-radiotherapy improves local control in patients with locally advanced rectal cancer, it can also increase acute hematological toxicity (HT), which leads to poor outcomes. Patients receiving bone marrow radiation have been shown to develop acute HT. However, the safety and efficacy of bone marrow sparing is undetermined. The aim of our study was to explore the feasible dosimetric constraints for pelvic bone marrow (PBM) that can be widely used in rectal cancer patients undergoing chemo-radiotherapy.Methods112 rectal cancer patients were selected and divided into the PBM sparing IMRT group (60 cases) and the non-PBM sparing IMRT group (52 cases). All patients underwent pelvic radiotherapy with concurrent capecitabine-based chemotherapy. The PBM dosimetric constraints in the PBM sparing IMRT group were set to:V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%. An independent sample t test was applied for the dose-volume parameters, and Chi-squared analysis was applied for clinical parameters and adverse events.ResultsThe radiation dose to PBM (V5~V45, Dmean, P<0.05), PBM sub-regions (V10~V35, Dmean, P<0.05) and both femoral heads (V5~V40, Dmean, P<0.05) decreased significantly in the PBM sparing IMRT group compared with that of the non-PBM sparing IMRT group (P<0.05). There was no significant difference in any dose-volume parameters of the bladder and small bowel in either groups, and none in the planning target volume (PTV) dose homogeneity and conformity (P>0.05). For acute HT observation, the incidence of grade 3 acute HT (χ2 = 7.094, P=0.008) was significantly reduced in patients treated with PBM sparing IMRT compared with patients treated with non-PBM sparing IMRT. There was no statistical difference in the incidence of vomiting, diarrhea, fatigue, anorexia, nausea, hand-foot syndrome, cystitis, perianal pain and perianal dermatitis in patients of both groups (P >0.05).ConclusionsApplying PBM dosimetric constraints (V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%) can significantly reduce the radiation dose to PBM. The patients treated with PBM sparing IMRT had a lower incidence of acute HT compared with those treated with non-PBM sparing IMRT. Applying the PBM dosimetric constraints proposed by our study can benefits the patients with rectal cancer undergoing capecitabine-based chemo-radiotherapy.

Outcomes of salvage radiation for recurrent world health organization grade II meningiomas: a retrospective cohort study.

The optimal modality of radiation-intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS)-in patients with recurrent WHO grade II meningiomas is not well-established. The purpose of this study was to compare progression-free survival (PFS) in patients undergoing salvage IMRT vs SRS. We compared PFS in those with and without history of prior radiation. Forty-two patients with 71 tumor recurrences treated with IMRT or SRS were retrospectively reviewed. Thirty-two salvage treatments were performed on recurrent tumors never treated with prior radiation ('radiation-naïve' cohort), whereas 39 salvage treatments were performed on recurrent tumors previously treated with radiation ('re-treatment cohort'). In the 'radiation-naïve' cohort, 3-year PFS for IMRT and SRS was 68.8% and 60.7%, respectively (p = 0.61). The median tumor volume for patients treated with IMRT was significantly larger than for patients treated with SRS (5.7 vs 2.2 cm3; p = 0.04). The 3-year PFS for salvage IMRT or SRS in the 're-treatment' cohort was 45.4% vs 65.8% in the 'radiation-naïve' cohort (p = 0.008). When analyzing the outcome of multiple re-treatments, median PFS was 47 months for 1st or 2nd salvage radiation (IMRT or SRS) compared to 16 months for the 3rd or greater salvage radiation treatment (p = 0.003). For salvage radiation of recurrent grade II tumors that are 'radiation-naïve', comparable 3-year PFS rates were found between IMRT and SRS, despite the IMRT group having significantly larger tumors. Salvage radiation overall was less successful in the 're-treatment' cohort compared with the 'radiation-naïve' cohort. Additionally, the effectiveness of radiation significantly declines with successive salvage radiation treatments.

Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial

To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D98% (31.1 vs 30.8 Gy, P < .0001), PTV D2% (37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V50% (24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V90% (9.1% vs 10.4%, P = .0003) and V80% (13.2% vs 15.7%, P = .0003). Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

Outcomes after radiation therapy for T2N0/stage II glottic squamous cell carcinoma.

We report outcomes for patients with T2N0M0 glottic squamous cell carcinoma (SCC) treated with radiation therapy (RT). Patients who received definitive RT for T2 glottic SCC from 2000 through 2013 were retrospectively reviewed. One hundred and thirteen patients were analyzed (median follow-up time 91 months; 85 patients received three-dimensional conformal radiotherapy [3D-CRT] and 28 received intensity-modulated radiation therapy [IMRT]). Fractionation was conventional (58%) or altered (42%); 20 patients (18%) received concurrent chemotherapy. Five-year local control was 83% for the 3D-CRT vs 81% for the IMRT group (P = .76). The ultimate locoregional control at 5 years was 100% for IMRT vs 91% for 3D-CRT (P = .1). The 5-year overall survival (OS) was 78% for 3D-CRT vs 81% for IMRT (P = .83). On multivariate analysis, younger age was the only independent predictor of improved OS (P = .0002). Oncologic and survival outcomes were excellent for patients with T2N0 glottic cancer. Patients treated with IMRT and 3D-CRT had no statistically significant differences in all investigated endpoints.