Start Of RT Research Articles

Dentist Involvement in the Treatment of Radiation-Induced Oral Mucositis-A Pilot Cross-Sectional Study.

Objectives: Oral mucositis (OM) occurs in more than 95% of patients irradiated in the head and neck area. This paper aims to determine the occurrence and characteristics of OM in patients with head and neck cancer (HNC), as well as the involvement of dentists/oral medicine specialists in treating such patients. Methods: This study was conducted at the Department of Otorhinolaryngology and Department of Oral Medicine, University Hospital Center Zagreb, from April to August 2022, on patients irradiated in the head and neck area. A unique OM questionnaire was created on the incidence, characteristics, oral care, and involvement of dentists in the overall care. Results: Thirty patients filled out the questionnaire. Of the 22 patients who had developed OM, 14 had grade-three OM. Ten patients were treated for OM in line with the instructions of an oral medicine specialist, eight based on the instructions of a specialist responsible for monitoring of the underlying disease, and four were not treated at all. Sixteen patients had not been referred to a dentist before the start of RT. Conclusions: These results showed insufficient care and treatment of OM, as well as insufficient involvement of dentists in the oncology team.

Biomechanical imaging biomarker during chemoradiotherapy predicts treatment response in head and neck squamous cell carcinoma

Objective. For response-adapted adaptive radiotherapy (R-ART), promising biomarkers are needed to predict post-radiotherapy (post-RT) responses using routine clinical information obtained during RT. In this study, a patient-specific biomechanical model (BM) of the head and neck squamous cell carcinoma (HNSCC) was proposed using the pre-RT maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose (FDG) and tumor structural changes during RT as evaluated using computed tomography (CT). In addition, we evaluated the predictive performance of BM-driven imaging biomarkers for the treatment response of patients with HNSCC who underwent concurrent chemoradiotherapy (CCRT). Approach. Patients with histologically confirmed HNSCC treated with definitive CCRT were enrolled in this study. All patients underwent CT two times as follows: before the start of RT (pre-RT) and 3 weeks after the start of RT (mid-RT). Among these patients, 67 patients who underwent positron emission tomography/CT during the pre-RT period were included in the final analysis. The locoregional control (LC), progression-free survival (PFS), and overall survival (OS) prediction performances of whole tumor stress change (TS) between pre- and mid-RT computed using BM were assessed using univariate, multivariate, and Kaplan–Meier survival curve analyses, respectively. Furthermore, performance was compared with the pre and post-RT SUVmax, tumor volume reduction rate (TVRR) during RT, and other clinical prognostic factors. Main results. For both univariate, multivariate, and survival curve analyses, the significant prognostic factors were as follows (p < 0.05): TS and TVRR for LC; TS and pre-RT FDG-SUVmax for PFS; and TS only for OS. In addition, for 2 year LC, PFS, and OS prediction, TS showed a comparable predictive performance to post-RT FDG-SUVmax. Significance. BM-driven TS is an effective prognostic factor for tumor treatment response after CCRT. The proposed method can be a feasible functional imaging biomarker that can be acquired during RT using only routine clinical data and may provide useful information for decision-making during R-ART.

Dental Extractions Before Radiation Therapy and the Risk of Osteoradionecrosis in Patients With Head and Neck Cancer

Patients with head and neck cancer undergo extraction of teeth with poor prognoses to minimize post-radiation therapy (RT) extractions, which are known to cause osteoradionecrosis (ORN). However, many patients are required to start RT before the extraction sites are completely healed. The role of pre-RT extractions in the development of ORN has been disputed in literature. To determine whether the timing of pre-RT dental extractions is associated with ORN development in patients with head and neck cancer. This retrospective cohort study was conducted at a single institution (Princess Margaret Cancer Centre, Toronto, Canada) between January 1, 2011, and January 1, 2018, and included 879 patients with head and neck cancer who underwent pre-RT dental extractions before curative RT of 45 Gy or greater. Patient demographic information and clinical characteristics (eg, primary cancer site, nodal involvement, chemotherapy, smoking status, dental pathology) were considered. Data analyses were performed from July to December 2022. Timing (number of days) from dental extractions to RT start date and pre-RT extractions categorized as healed, minor bone spicules (MBS), or ORN. The study population consisted of 879 patients with a median (range) age of 62 (20-96) years, with 685 men (78%) and 194 women (22%). Of these, 847 (96.3%) healed from pre-RT dental extractions, 16 (1.8%) developed MBS, and 16 (1.8%) developed ORN. The median (range) time in number of days from pre-RT extraction(s) to start of RT was 9 (0-98) days in the healed cohort, 6 (3-23) days in the MBS cohort, and 6 (0-12) days in the ORN cohort. There was a large difference in the timing of pre-RT extractions between the healed and the MBS cohorts (mean 11.9 vs 7.4 days to radiation; difference 4.4; 95% CI, 1.5-7.3), and the healed and the ORN cohorts (mean 11.9 vs 7.1 days; difference 4.8 days; 95% CI, 2.6-7.1). The findings of this retrospective cohort study suggest that there was an important association between the timing of pre-RT dental extractions and ORN when extractions occurred within 7 days of the RT start date. Despite this, ORN after pre-RT extractions is relatively rare. These findings indicate that patients with head and neck cancer who are to undergo RT should not delay treatment for extractions when it might compromise oncologic control.

Pre-Treatment Trends in Child-Pugh Score as an Indicator of Post-Treatment Survival in Patients Receiving Liver SBRT for HCC

We sought to understand the value of Child-Pugh (CP) score trends prior to undergoing stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma in patients with advanced cirrhosis, as an indicator of post-treatment morbidity and mortality. We hypothesize that an uptrend in CP score prior to RT increases risk of post-treatment cirrhosis progression, or death. We retrospectively reviewed all patients who underwent definitive SBRT for HCC between 2014-2022 in our health system. Most patients were referred for treatment in the 2nd or 3rd line setting, allowing us to determine CP score at multiple points before SBRT. Response to treatment was evaluated with RECIST or mRECIST criteria. Acute treatment toxicities were assessed by CTCAE v5. OS was assessed using the Kaplan-Meier method, and differences between groups were evaluated using log-rank test. A total of 61 patients were identified, 26 had an immediate pre-SBRT CP score of A5, 11 with A6, 10 with B7, 4 with B8, 4 with B9, 5 with C10, and 1 with C11. Median prescribed dose was 40Gy in 5fx. Median OS of all patients was 24 months. When stratified by CP category, median OS for CP A was not reached (NR) at time of analysis, CP B had a median OS of 14.8mo, and CP C with 1.9mo (p < 0.01). Local control rate at 6mo was 87.5%. 5 patients (8.3%) had CTCAE grade 2 acute toxicity. 10 patients had CP score progression of 2pts or more within 6mo after treatment, and 7 patients had a cause of death attributed to end stage liver disease. Median time interval between HCC diagnosis and start of RT was 338 days. In this time interval, patients with a CP score increase of 2 pts or more prior to starting RT had a median OS of 362 days, compared to NR for patients without increase (p = 0.02). When excluding the CP A group, patients with 2 pt increase had median OS of 362 days vs 445 days (p = 0.34). Again excluding the CP A group, patients with a 1 pt increase had median OS of 362 days vs NR (p = 0.23). Of 9 patients who had a pre-RT CP score increase of 2 pts or more, 7 experienced continued CP progression after treatment. In this multi-institutional retrospective analysis, we found 24 patients with advanced CP B/C cirrhosis who underwent SBRT, none of whom received orthotopic liver transplant. While CP C patients did relatively poorly, we find that some patients with CP B cirrhosis may tolerate SBRT well with good oncologic effect. When taking pre-treatment CP score increase into consideration, we saw a trend but no statistical significance indicating that a pre-SBRT increase in CP score may be associated with worse OS after treatment among CP B/C patients. We conclude that there may be a subset of patients with advanced cirrhosis who, if well selected, are appropriate candidates for SBRT. We suggest a novel use of the CP score and pre-RT trends as an additional clinical tool to aid in decision making when selecting patients. We also suggest that patients with marked up-trending scores pre-treatment have a high likelihood of continued cirrhosis progression after treatment.

A Novel CT-Based Radiomic Analysis for the Prediction of Overall Survival in Rectal Cancer Patients Treated with Short Course RT Total Neoadjuvant Therapy

Radiomics is a method based on the extraction of features from medical images, enriching the construction of predictive models for aiding patient management. The purpose of this study is to develop a model based on radiomic features for the overall survival (OS) in rectal cancer patients treated with total neoadjuvant therapy (TNT). Prediction of neoadjuvant rectal (NAR) score was also preliminarily evaluated. A retrospective cohort including patients treated with TNT at a single center between 2017-2021 was identified. TNT consisted of short course pelvic radiotherapy (25 Gy in 5 fractions) followed by FOLFOX or XELOX. A single CTV included mesorectum and nodal regions. Two endpoints were used: OS at 3 years (from the start of RT) and NAR score binary classification. A cut-off of 8.4 was used for NAR based on a previous local study. CTV radiomic features were extracted from simulation CTs using Pyradiomics v3. Features were extracted from the unfiltered images as well as from a set of eight filtered images. Radiomic features consist of 7 classes: shape, first order statistics, glcm, gldm, glrlm, glszm and ngtdm. 1967 initial features were extracted. Features with 0 standard deviation were removed as well as highly correlated ones (0.99 Pearson Coefficient). Dimension reduction using PCA was applied to each feature class, preserving 95% of the explained variance. Supervised algorithms were evaluated using a 10-fold cross-validation technique. Demographic and clinical features were also considered (age, sex, cT stage and N positivity) RESULTS: Eighty-two patients were included (37 females). Median age was 61.5 years (IQR 53-70). Clinical staging was comprised of 5 cT2 patients, 57 cT3 and 20 cT4, with 69 cN+. 3y-OS was 72%, with a median follow-up of 43.7 months (IQR 35.3-48.6). For the 3y-OS endpoint two prediction models were developed. First, a reference model (KNN classifying algorithm) based on demographic and clinical features only resulting in an AUC of 0.659 (SD 0.029). The second model (CART classifying algorithm) included demographic, clinical and radiomic features resulting in an AUC of 0.744 (SD 0.032). For the binary NAR classification model, a subset of 77 patients was used. Twenty-three presented a NAR<8.4 and 54 a NAR≥8.4. The CART algorithm presented the best performance with an AUC of 0.808 (SD 0.037) considering demographic, clinical and radiomic features. Radiomic models were developed for 3y-OS prediction and binary NAR classification. The addition of radiomic features to clinical and demographic information improved the predictive capability of the 3y-OS model. Radiomic prediction of NAR makes it a promising tool for the identification of potential short course RT TNT responders.

Differential Response in Quantitative MRI Parameters Detected in Head and Neck Cancer Patients Treated with Concurrent Immunotherapy during Hypo-Fractionated MR-gRT

Recently, multiple clinical trials have demonstrated success of PD-1/PD-L1-targeted immune checkpoint inhibition (ICI) in recurrent and metastatic head and neck cancer (HNC). However, three large clinical trials combining PD-1/PD-L1-targeted ICI with RT or chemo-RT (CRT) in the definitive management of HNC have shown no benefit of combination therapy with ICI over RT or CRT alone. Our overarching hypotheses are: i) hypo-fractionation may ultimately better synergize with ICI compared to conventional RT regimens, and ii) immunologic changes in the tumor microenvironment may be detectable using quantitative MRI (qMRI) parameters collected during RT. Seven patients treated with hypo-fractionated MR-guided RT of 50 Gy in 15 fractions (DEHART, NCT04477759) were included in the study. Four patients (Group 1) were treated with concurrent atezolizumab (a monoclonal antibody) and three patients (Group 2) were treated with RT alone. Daily DWI, T1 mapping, and T2 mapping sequences were acquired on a 1.5T MR-Linac in the idle time during adaptive plan generation. Median ADC, T1, T2, and Dslow (derived from b-values 150 and 550 s/mm2) values were extracted from physician-defined GTV and manually constructed posterior paraspinal muscle contours, the latter serving as a control. Wilcoxon signed rank tests were conducted using pre/post treatment data for each qMRI parameter. GTV ADC, Dslow, T2, and T1 increased for both patient groups over the course of treatment with significant differences in ADC, Dslow, and T2 detected between fractions 1 and 15 for all patients studied (p = 0.0156, p = 0.0156, and p = 0.0469, respectively). No significant differences were detected in control qMRI parameters pre/post treatment. No significant differences in ADC, Dslow, and T2 were detected between groups' fractions 1 and 15 in these small cohorts. However, interestingly, we observed a differential change in the increase of median GTV T2 and Dslow values during fractions 10-12 in Group 1 compared to Group 2, suggesting this time interval may prime the anti-tumor immune response. Combining hypo-fractionated RT with ICI leads to a differential response in quantitative MRI (qMRI) parameters in HNC patients. These results suggest that qMRI parameter changes ten days following the start of RT may reflect a critical juncture in the anti-tumoral immune response when ICI is combined with hypo-fractionated RT.

A Single-Institution Experience of Acute Neuropathic Lumbosacral Pain in Patients Treated with Short Course Hypofractionated Radiotherapy in Locally Advanced Rectal Cancer

There has been increased interest in the use of short course hypofractionated radiotherapy as part of a total neoadjuvant treatment (TNT) approach in the management of rectal cancer since publication of the RAPIDO trial. However, the literature on short course radiation for rectal cancer has not reported significant acute toxicities in the weeks immediately following the completion of treatment. Anecdotally, a subset of patients has experienced acute neuropathic pain characterized in a lumbosacral distribution. This study investigates acute lumbosacral toxicity for patients receiving hypofractionated short course radiation as part of their definitive treatment for rectal cancer. We retrospectively analyzed 75 patients with locally advanced rectal adenocarcinoma treated with hypofractionated short course radiation (25 Gy in 5 fractions) at our institution between 2016 and 2022. Acute toxicity caused by radiation was defined as that occurring from the start of radiation treatment to either 30 days post radiation completion, the start of chemotherapy, or date of surgery, whichever occurred first. Among 75 patients treated with hypofractionated short course preoperative radiation with definitive intent, we identified 10 patients (13.3%) who experienced significant lumbosacral neuropathic pain and initiated a report to their medical providers during the acute toxicity time frame. Commonly, this was described as an achy pain in the bilateral buttocks radiating down to the knees or posterior claves. Patients rated this pain between moderate to extreme and management included steroids after failure of improvement with conservative measures, gabapentin, and conservative treatment with NSAIDs and Tylenol. Average time to onset of acute lumbosacral neuropathic pain was 3.7 days (SD 2.05) from start of RT. We have identified a previously underappreciated acute toxicity of neuropathic lumbosacral pain in short course hypofractionated radiation therapy, which may be due to a lumbosacral plexus toxicity. Further analysis will seek to identify predictive factors such as comorbidities and dose to the lumbosacral plexus, and to determine whether there is a correlation between these observed acute toxicities and long-term outcomes.

Multi-Institutional Phase I Feasibility Trial of Vertebral Body Sparing CSI for Pediatric Brain Tumors

Craniospinal irradiation (CSI) is an essential part of curative treatment for several pediatric brain tumors. Proton CSI allows for sparing of the organs anterior to the vertebral bodies (VBs), but this technique still includes the entire VB in the target for growing children. providing no advantage in marrow sparing or adverse effects on growth. Advances in proton therapy including Proton Beam Scanning (PBS) allow for delivery of proton CSI with substantial vertebral body sparing (VBS). We sought to determine the feasibility of VBS CSI using PBS based on the effects on tumor control and growth, and the occurrence of grade III/IV hematologic toxicity. Clinical and treatment characteristics were recorded for 20 pediatric patients with medulloblastoma (n = 14) or germ cell tumor (GCT) (n = 6) who received proton VBS CSI without concurrent chemotherapy or with concurrent single-agent vincristine in a multi-institutional clinical trial. The following standard variables were extracted for each patient: age, histology, radiation dose, chemotherapy regimen, and growth hormone replacement status. Complete blood counts (CBC) with differential and data on height/weight were recorded at baseline pre-RT, weekly during RT, and after completion of cancer treatment. Hematologic toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (CTCAE v4). Median age of 13 male and 7 female patients receiving proton VBS CSI was 10 years (range: 5.1 - 15.1). All GCT patients (n = 6, 30%) received pre-RT chemo. Median CSI dose was 23.4 Gy (range: 21.0 - 37.8), and total dose to tumor bed was 54 Gy in 18 patients (90%) while 2 patients with pure germinoma received a total dose of 36 and 37.5 Gy, respectively. 11 patients (55%) did not receive concurrent vincristine. At a median follow up of 26.4 months (range: 12.5 - 56.3) from the start of RT, no patients relapsed. 17 patients (85%) developed grade ≥3 hematologic toxicity including grade 3 lymphopenia (n = 16), leukopenia (n = 9), neutropenia (n = 8), anemia (n = 1), and grade 4 neutropenia (n = 1). The patient who developed grade 4 neutropenia had low white blood counts prior to RT. 14 patients (70%) received post-RT chemo. No patients required platelet transfusion during RT. Those findings are similar to historical controls. 4 patients started growth hormone replacement therapy after RT. No patients developed spine deformities after the completion of treatment. Proton VBS CSI is a feasible and well tolerated treatment for children with brain tumors. Longer follow up is needed to assess for late effects on tumor control. It is too early to assess for height in this cohort but for the patients that had longer follow up, normal height was achieved.

HYPOCx-iRex (TCTR20210812003) A Phase II RCT: 44 Gy/20F VS 45 Gy/25F CCRT in Cervical Cancer: Six-month Post-RT Update

Hypofractionation for definitive concurrent chemoradiation (CCRT) in locally advanced cervical cancer (LACC) may increase RT efficacy but scarce in data. Early results of HYPOCx-iRex trial at 3-mo follow-up (F/U) time showed a non-statistically significant small rise but auto-resolved acute GI toxicity of HYPO 44 Gy/20F arm compared to CVRT 45 Gy/25F arm, yet significantly retracted overall treatment time and time to brachytherapy without compromised GTV reduction or tumor response. This prespecified interim analysis at 6-mo post-RT of the first 20 patients was intended to prove non-inferior late toxicity, oncologic outcome and pattern of failure of HYPO in addition to previous ESTRO2023 abstract. Patients with LACC were enrolled since July 2021. ≥3 Pelvic LN or at/above common iliac were excluded to omit paraaortic RT. Open-label randomization was performed for IMRT/VMAT to HYPO for 44 Gy/20F to whole pelvis and 53 Gy/20F SIB to gross LN in five-day-a-week fractions, and for CVRT 45 and 55 Gy/25F, with concurrent weekly cisplatin 40 mg/m2. Target contour and planning dose of EBRT and IGABT were adapted and biologically converted from EMBRACE-II. Indirect ratio of excess dose volume (iRex; DOI: 10.5114/jcb.2020.100377) as a complimentary low-dose conformity index to D2cc-based IGABT was explored, but analysis was out of this abstract scope. Non-inferiority margin of 9% 5-yr GI toxicity difference of HYPO and CVRT with one-sided α = 0.5 and 1-β = 0.8 yielded 40-patient sample size for toxicity screening. Adopting 9% margin, analysis at 6-mo post-RT of the first 20 patients were done with descriptive and survival analysis. Twenty-nine patients with median F/U time from start of RT of 8 months were included. Non-significant difference of IGABT dose was seen. Median post-RT time were 7 months with non-significant difference in 6-mo crude, late and persistent (LAPER), or cumulative GI and GU toxicity. Unfortunately, difference of -0.07 [95% CI -0.47 to +0.32] cumulative GI toxicity exceeded margin of +0.09, but the p value is greater than 0.5 (cut-off for go or no go for phase III study). No significant oncologic outcome nor pattern of failure difference were shown. HYPO 44 Gy/20F showed trend of non-significant difference in 6-mo toxicity nor oncologic outcome. The unmet non-inferior margin should be re-evaluated at trial completion for further implementation.

Irradiation dose to the swallowing apparatus impacts nutritional status in head and neck cancer patients—results from the prospective randomized HEADNUT trial

PurposeTo investigate the influence of radiation dose to the swallowing muscles on the nutritional status in patients with head and neck cancer undergoing primary or adjuvant (chemo)radiotherapy (C)RT.MethodsBetween 2018 and 2020, 61 patients were prospectively randomized into the so-called HEADNUT trial (head and neck cancer patients undergoing nutritional intervention). Follow-up was continued until 2022. Contouring of the swallowing apparatus included the superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeal muscle (cphm), and the esophageal inlet. Nutritional status was assessed by bioelectrical impedance analysis (BIA) at the beginning and the end of radiotherapy. The posttherapeutic nutritional status was evaluated by the BIA-derived fat-free mass index (FFMI; kg/m2). Malnutrition was assumed at FFMI values of < 15 (women) and < 17 (men) kg/m2. To find differences between dosimetric parameters in well- and malnourished patients, Mann–Whitney U test was used. To model the association between malnutrition and its potentially influencing variables, several logistic regression models were built.ResultsThe following parameters differed between well- and malnourished patients at the end of therapy: icm Dmean, V40Gy (%), V50Gy (%), and V60Gy (%), and sphm V40Gy (%). After entering these parameters into a multivariable logistic regression model (dosimetric model), icm Dmean (b = −0.12; Exp(b) = 0.88; 95% CI: 0.78–1.0; p = 0.06) and icm V40Gy (%; b = 0.06; Exp(b) = 1.07; 95% CI: 1–1.13; p = 0.04) proved to be independent dosimetric predictors of malnutrition. We only determined the cut-off value for predicting malnutrition for icm V40Gy (%) since it was the only parameter which met p < 0.05. The optimal cut-off value for the predictor V40Gy (%) based on the Youden Index was 85.6%. Another logistic regression model (dosimetric-clinical model) consisted of icm V40 (%) and the clinical parameters tumor localization, malnutrition before RT, gender, and combined chemotherapy. It was confirmed that both icm V40% (b = −1.9; Exp(b) = −2.7; 95% CI: 0.01–0.8; p = 0.03) and malnutrition at baseline (b = −1.9; Exp(b) = 4.4; 95% CI: 8.4–816.6; p = 0.0002) were independent predictors of subsequent malnutrition the end of RT.ConclusionEstablishment of a normal nutritional status before the start of RT and adherence to dose constraints for the swallowing apparatus may prevent malnutrition in head and neck cancer patients at the end of therapy. Specifically, we suggest an icm V40Gy (%) of more than 86% to be predictive for nutritional complications.

Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203

IntroductionNRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments. MethodsNRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4–6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05. ResultsNRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, −5.04, compared to patients treated with 3DCRT, −7.48, although not statistically significant (p = 0.38). ConclusionThis is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints.

Breast Reconstruction Outcomes with Immediate Reconstruction Followed by Proton or Photon Postmastectomy Radiotherapy

<h3>Purpose/Objective(s)</h3> To evaluate breast reconstruction outcomes among women undergoing immediate breast reconstruction (IBR) followed by postmastectomy radiotherapy (PMRT) with photon or proton radiotherapy. <h3>Materials/Methods</h3> We identified consecutive women with breast cancer who underwent IBR followed by unilateral PMRT at our institution from 2015 to 2021 and retrospectively reviewed reconstruction complications. IBR failure was defined as tissue expander or implant removal with loss of reconstruction or conversion to autologous reconstruction. Patient, disease, and treatment characteristics were assessed for association with complications using univariate Cox models. When analyzing the impact of RT-related variables, only complications occurring after the start of RT were included. <h3>Results</h3> Following IRB approval, 225 women were identified as eligible. One-hundred seventy-five (77.8%) elected to undergo prophylactic mastectomy and IBR for symmetry. Two-hundred eighteen patients (96.9%) had two-stage tissue expander-based IBR, and seven (3.1%) had direct-to-implant IBR. One-hundred sixty women (71.1%) were treated with proton therapy. Most (198, 88%) received 50 Gy in 25 fractions, with the remainder receiving 40.05 Gy in 15 fractions (25, 11.1%) or 42.56 Gy in 16 fractions (2, 0.9%). Seven (3.1%) and 28 patients (12.4%) received a boost to the chest wall and lymph node(s), respectively. At a median follow-up of 1.8 years, the 2-year risk of any complication on the irradiated side was 31.4% (24.4-38.3). This is compared to a contralateral risk of 15.0% (9.4-21.7) among the 175 bilateral mastectomy patients. Seventeen patients (7.6%) experienced an ipsilateral IBR failure, six of whom had no final reconstruction. The remaining 11 patients had an autologous reconstruction, two of whom initially planned for autologous reconstruction. There were no contralateral IBR failures. On univariate analysis, increasing age [HR per year: 1.10 (1.05-1.15), <i>p</i><.001], chest wall boost [HR: 4.81 (1.08-21.35), <i>p</i>=.039], and lymph node boost [HR: 3.97 (1.35-11.63), <i>p</i>=.012] were associated with IBR failure. There was no significant difference in IBR failure with protons compared to photons. Administration of capecitabine concurrently with RT predisposed to any complication [HR: 7.97 (1.91-33.33), <i>p</i>=.040], while use of Mepitel film during PMRT was protective [HR for no Mepitel: 1.85 (1.12-3.06), <i>p</i>=.017]. Receipt of neoadjuvant or adjuvant systemic therapy and concurrent T-DM1 were not associated with complications or IBR failure. <h3>Conclusion</h3> Among women who undergo IBR, receipt of PMRT increases the risk of complications by approximately twofold. To our knowledge, this is the largest report on women receiving IBR and proton-based PMRT. There was no difference in IBR failure with protons compared to photons. Despite nearly one-third experiencing complications with IBR and PMRT, most women (92.4%) achieved a successful reconstruction outcome.

Radiation Therapy (RT) Quality Assurance (QA) Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas (PDAC)

<h3>Purpose/Objective(s)</h3> Alliance A021501 is the first national clinical trial to test the efficacy of stereotactic body radiation therapy (SBRT) in patients with PDAC. Herein, we aim to (1) review metrics used to provide high quality RT; (2) assess reasons for protocol deviations; and (3) analyze potential inter-observer variability with respect to contouring. <h3>Materials/Methods</h3> Each site was required to undergo credentialing prior to RT through IROC Houston. A tutorial for RT contouring and planning was recommended. Patients received SBRT (6.6 Gyx5) (strongly preferred) or hypofractionated RT (5 Gyx5) (HIGRT). Compliance criteria was provided for the target volume coverage and organs-at-risk (OARs). All cases required pre-treatment review by an experienced radiation oncologist (RO, TJ). Fiducials and daily imaging were required. Unacceptable deviations from the protocol were resubmitted for review and revised until approved. Cases requiring revision were carefully analyzed. RT plans were independently graded by 3 ROs with respect to several QA parameters. <h3>Results</h3> 40 patients were registered to receive RT (1 case planned but not treated) at 27 centers by 34 ROs. 16 centers were academic, 9 community. Centers were credentialed for an average of 3 years prior to enrollment (range: 0-9). 11 centers (6 academic, 5 community) required at least 2 attempts to pass credentialing. 23 centers were approved for moving lung/liver targets and 4 for static head and neck only. 33 patients were treated with SBRT, 6 with HIGRT. 5 cases (13%) required revision prior to RT. 54% patients (n=21) were female with a median age of 67 years. Time from enrollment to the start of RT was on average 117 days. Target and OAR volume data is shown in the Table. Motion management involved abdominal compression (33%), free breathing with increased margin (23%), or gating (23%). A median of 3 fiducials per case were used (range: 1-5). Details related to on-treatment delivery and image guidance were not recorded. Any deviations related to contouring or RT plans will be correlated with toxicity and outcomes. <h3>Conclusion</h3> There were no major deviations in RT planning. Variations in contouring, image fusion, and the potential influence of dose/fractionation differences on outcomes will be presented at the meeting. The results of this study serve to inform subsequent PDAC SBRT trial design and QA requirements.

Patient-Reported Rectal QOL with Pelvic Nodal Irradiation ± Involved Pelvic Nodal Boost to 75 Gy EQD2 in Men with Prostate Cancer

<h3>Purpose/Objective(s)</h3> The study was designed to compare patient-reported acute and late rectal function quality of life (RQOL) between men with local or regional prostate cancer treated with or without an involved pelvic nodal simultaneous integrated boost (SIB). It is hypothesized that men receiving pelvic nodal radiotherapy at 50.4 Gy in 28 fractions (Pelv50) have similar RQOL as men receiving the same pelvis dose plus the addition of involved pelvic nodal SIB to 67.2 Gy in 28 fractions (Pelv67). <h3>Materials/Methods</h3> Rectal toxicity was assessed using the Merrick Rectal Function Assessment Score (R-FAS). The R-FAS consists of nine questions and a scoring range of 0-27, with higher scores indicating poorer bowel function. Patients with measures -180 days and up to 730 days from the start of RT were included in the analysis. SIB targets included radiographically apparent nodal GTVs plus a 5mm margin. Pelvic nodal contours extended from aortic bifurcation through the bilateral obturator nodes. An EQD2 of 75 Gy to involved nodal targets was calculated for the Pelv67 group based on 28 fractions of 2.4 Gy with an α/β ratio of 1.5. Patients were dichotomized by treatment received (Pelv50 vs. Pelv67). Non-parametric kernel regression was modeled with R-FAS score as the dependent variable and time from RT and treatment cohort as the independent variables, with improved Akaike information criterion to determine optimal bandwidth. Marginal means and 95% confidence intervals were predicted at 90-day intervals from timepoint 0 with 50 bootstrapping replications. <h3>Results</h3> There was no difference in baseline age or baseline Charlson Comorbidity Index between the two cohorts. There was no significant difference in mean R-FAS over the entire time interval between the two cohorts (Pelv67 vs. Pelv50: 0.4 points, p=0.17). There is no significant difference in R-FAS score at any discrete timepoint between Pelv67 and Pelv50 as the 95% confidence intervals overlap (Table). <h3>Conclusion</h3> Pelvic nodal irradiation with a simultaneous integrated boost to 67.2 Gy in 28 fractions (EQD2=75 Gy) was associated with similar rates of RQOL compared to standard pelvic irradiation from the patient's perspective. This study suggests that dose escalation using a pelvic nodal SIB technique to 75Gy EQD2 is safe despite the proximity of the rectum and bowel to SIB targets.

FOLFOX-Based Chemoradiation as Non-Operative Management for Esophageal Adenocarcinoma

<h3>Purpose/Objective(s)</h3> Nonsurgical treatment with chemoradiation (CRT) alone is less commonly recommended for esophageal adenocarcinoma (EAC) compared to squamous cell carcinoma, due to lower rates of complete response. However, the CALGB 80803 trial indicates that FOLFOX-based CRT can achieve higher rates of pathologic complete response compared to the CROSS-trial regimen of carboplatin/paclitaxel. We reviewed our institutional experience to identify patients who received FOLFOX-RT for localized EAC without surgery, hypothesizing that they may experience relatively favorable survival and local control with CRT alone. <h3>Materials/Methods</h3> A retrospective study was conducted on patients with esophageal or gastroesophageal junction adenocarcinoma who received CRT for Stage I-III disease at our institution. We extrapolated patients who received RT dose ≥41.4Gy with FOLFOX or capecitabine/oxaliplatin chemotherapy prior to or concurrent with RT, and did not undergo post-CRT surgical resection. Overall survival was calculated from the start of RT using Kaplan-Meier method, and local recurrence-free survival (LRFS) was assessed in patients with negative post-CRT endoscopic biopsies. <h3>Results</h3> 440 consecutive patients who received CRT between 2016-2021 for esophageal/GEJ adenocarcinoma were reviewed. Excluding patients who did not receive FOLFOX or CAPOX chemotherapy, and/or underwent post-CRT surgery, yielded a total of 50 patients for whom FOLFOX-RT served as definitive treatment. 45 patients received induction chemotherapy prior to CRT. 33 patients underwent post-CRT endoscopic biopsy, of which 22 showed no detectable malignancy. 15 of these patients declined surgery due to the apparent complete response, while the other 7 were medically inoperable. At two years, survival was 100% in biopsy-negative/medically operable patients, 93.8% in all biopsy-negative patients, and 46.7% overall. Median survival was 23.7 months, and 45.0 months in biopsy-negative, medically operable patients. 6 of the 22 patients with negative post-CRT biopsy have experienced local tumor recurrence, and median LRFS in this group was 27.2 months. <h3>Conclusion</h3> To our knowledge, this is the first report describing outcomes of non-surgical management in patients receiving FOLFOX-based CRT for esophageal/GEJ adenocarcinoma. Survival outcomes with this approach appear favorable, particularly among patients with negative post-CRT biopsy. This data suggests that patients achieving clinical complete response to FOLFOX-RT can have excellent prognosis even without surgery. FOLFOX-based CRT has promise as a basis for non-operative treatment approaches in esophageal/GEJ adenocarcinoma.

Multi-Institutional Evaluation of Health Disparities in Rural Cervical Cancer Patients

<h3>Purpose/Objective(s)</h3> Cervical cancer remains a significant concern for both rural and urban populations in the US. Overall treatment time from the start of chemoradiation to completion of brachytherapy is known to correlate with local control and overall survival. Rural populations experience health disparities which are multi-factorial and vary by region, but a commonality is lack of healthcare access and distance to tertiary care centers. The purpose of this study is to examine the health disparities due to geographic location for women with locally advanced cervical cancer (LACC) presenting to tertiary care facilities and identify factors that influence their treatment and outcomes. <h3>Materials/Methods</h3> A multi-institutional retrospective cohort study was conducted including data from 5 tertiary care centers across the United States. Women with LACC defined as FIGO 2018 IB3-IVA treated with definitive intent RT ±chemotherapy from Jan 2011 to Jan 2021 were included. Clinical, pathologic, radiologic, demographic, and treatment parameters as well as disease outcomes were collected. Geographic location was collected, and zip code was used to determine urban (pop ≥10,000) or rural (pop <10,000) residency. Univariate analyses were used to determine the effects of these variables on disease outcomes. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. <h3>Results</h3> 613 patients were included from diverse regions of the country. Median OS was 27 months (range 0-133) and median RFS was 19.4 months (range 0-123.5). Urban (N=534, 87%) or rural (N=79, 13%) residence was not correlated with overall treatment time (p = 0.50) or cervical cancer specific survival (p = 0.32). The median time from diagnosis to start of RT was significantly shorter in the rural patient population than in the urban population (28 days v. 41 days, p = 0.002). There was no significant association between time from diagnosis to start of RT and cervical cancer specific survival (p = 0.07) or between overall treatment time and cervical cancer specific survival (p = 0.26). There was, however, a significant association between overall treatment time and time to recurrence, with each day of increase in treatment time leading to a 1.1% increased risk of recurrence (p = 0.03, HR = 1.011). <h3>Conclusion</h3> In this group of patients we found no differences in treatment time or outcomes between urban and rural residents and surprisingly, rural patients had a shorter median time from diagnosis to start of treatment when compared to the urban patient group. As is already known, there was a significant relationship between treatment time and time to recurrence, highlighting the importance of timely treatment in patients with LACC. We are adding data from several more centers and will be evaluating the populations with more granularity to identify challenges faced by our patients and resources that may be helpful.

Surgical Outcomes of Laparoscopic Pelvic Lymph Node Debulking during Staging Aortic Lymphadenectomy in Locally Advanced Cervical Cancer: A Multicenter Study.

Simple SummaryLymph node metastasis is an important prognostic factor in locally advanced cervical cancer (LACC), which makes correct staging crucial. In contrast to existing studies evaluating pelvic lymphadenectomy after aortic lymphadenectomy, this study focuses on the pelvic node (PLN) debulking technique which has the dual objective of staging and cytoreduction. This is a multicenter retrospective study of patients with LACC and positive pelvic nodes on imaging tests. Feasibility, morbidity and delay in the initiation of chemoradiotherapy (CRT) were evaluated for the PLN debulking by comparing it with a control group of aortic lymphadenectomy alone. Excision of the bulky nodes was possible in 99.4% of patients. There were no differences in complications between the groups and a shorter time from diagnosis and from surgery to the start of CRT was observed in the study group.Background: Few studies have evaluated laparoscopic pelvic lymph node (PLN) debulking during staging aortic lymphadenectomy in locally advanced cervical cancer (LACC). It allows us to know the lymph node status and facilitates the action of chemoradiotherapy (CRT) by reducing tumor burden. We evaluated its feasibility and compared the perioperative morbidity and the time to CRT with a control group. Methods: This was a multicenter retrospective study of patients with LACC FIGO stage IIIC1r who were recipients of CRT. We compared two cohorts: group 1, which consisted of 164 patients with surgical staging by laparoscopic aortic lymphadenectomy and PLN debulking, and group 2, which consisted of 111 patients with aortic lymphadenectomy alone. Results: Excision of the bulky nodes was possible in all patients in group 1 except for one. Surgery lasted a median of 82 min longer in group 1 but there was no greater intraoperative bleeding or increased hospital stay. There were no significant differences in intraoperative or postoperative complications between the groups. A significantly shorter time from surgery to the start of RT was observed in group 1. Conclusions: It is feasible to perform laparoscopic PLN debulking in the same procedure as the staging aortic lymphadenectomy in LACC without increasing surgical or postoperative complications and without delaying the start of CRT compared to single aortic lymphadenectomy.

Vaginal mucositis in patients with gynaecological cancer undergoing (chemo-)radiotherapy: a retrospective analysis

The objective of this retrospective analysis was to determine the incidence and extent of vaginal mucositis (VM) in women with gynaecological cancer undergoing external (chemo)radiation therapy (CRT). A retrospective analysis was set up to collect data on the incidence and severity of VM in women treated with external pelvic RT for gynaecological cancer at the Jessa Hospital, Hasselt and ZOL, Genk, BE between January 2017 and June 2018. At the start and end of their external (C)RT, they rated the frequency and intensity of five common symptoms of VM. Thirty-three patients treated with RT for gynaecological cancer met the inclusion criteria. A non-negligible proportion of patients already experienced at least one VM symptom to any degree before the start of RT, a proportion that further increased towards the end of the RT (73%). At the end of RT, on average, about 25% of these patients reported moderate-to-severe symptoms (against about 7% before the (C)RT). These results suggest that VM is a rather frequent side effect in gynaecological cancer patients that aggravates during treatment up to a moderate severity level. Although the small sample size, these data highlight the need for attention to VM. Impact Statement What is already known about this topic? Radiotherapy plays an important role in the treatment of gynaecological malignancies. A debilitating complication in patients undergoing pelvic radiotherapy is vaginal mucositis, an inflammation of the vaginal mucosal lining. To date, the incidence of vaginal mucositis is still not well documented. What this paper adds? A non-negligible proportion of patients already experienced at least one symptom related to vaginal mucositis before the start of radiotherapy. Most patients presented mild to moderate vaginal mucositis symptoms at the end of external pelvic radiotherapy. Burning sensation, pruritus, and pain were the most frequently documented radiotherapy-induced complications. The implications of this paper: Vaginal mucositis is an underrated side effect of pelvic radiotherapy that needs to be tackled multidisciplinary by a team of nurses, radiotherapists, oncologists, and gynaecologists. The team should tackle the complication from the start of radiotherapy by using the most appropriate measures. Due to a possible link between acute vaginal mucositis and late vaginal toxicity, the team needs to follow-up patient’s post-radiotherapy to support patients in late complications and advise/encourage patients in performing vaginal dilatation to prevent vaginal stenosis.

ASSESSMENT OF DISTRESS DYNAMICS AND QUALITY OF LIFE OF CANCER PATIENTS AT THE STAGE OF RADIATION THERAPY AND POSSIBILITIES OF THEIR CORRECTION.

to assess the dynamics of psycho-emotional status and QOL of cancer patients at the stage of radiation therapy. The study involved psychodiagnostic examination of 66 cancer patients who underwent radiation treatment in the clinic of the State Organization «Grigoriev Institute for Medical Radiology and Oncology of the NAMS of Ukraine», of whom Group 1 included 44 patients with head and neck cancer, Group 2 comprised 22 patients with colorectal cancer. Comparison group comprised 30 conditionally «healthy» respondents without cancer. All patients had stage III-IV cancer. The study implied the employment of «Distress Thermometer», Hospital Anxiety and Depression Scale (HADS), and the SF-36 Questionnaire (Short Form). The examination was performed before and following the course of radiation therapy. Group 1 patients underwent only psychodiagnostic examination, Group 2 patients apart from psychodiagnostic were accompanied by a psychologist before undergoing radiation procedures. In the comparison group, the survey was conducted once. Assessment of the data showed that before the start of RT most subjects (72.73 % in Group 1 and 77.3 % in Group 2) had a high level of distress, they were worried and nervous before the first radiation procedure, had fears about the consequences and side effects. The level of anxiety in Group 1 at the pathological and subclinical level was recorded in 54.55 % of patients, the rate of depression at the subclinical level was diagnosed in 18.20 %, and in 9.10 % of patients at the clinical one. In Group 2, the level of anxiety that exceeded the norm was recorded significantly less often (27.25 % vs. 54.55 %, pt < 0.05), and the rate of depression at the subclinical level was diagnosed significantly more often than in Group 1 (54.50 % vs. 18.20 %, pt < 0.05), and in 18.2 % of patients at the clinical level. After radiation, 81.81 % of Group 1 patients showed an increase in distress and anxiety, and depressive symptoms tended to worsen. The level of distress in Group 2 after consulting a psychologist in preparation for RT and undergoing radiation procedures decreased almost twice, the level of anxiety decreased to normal, the indicators of depressive symptoms remained unchanged. According to QOL assessments on the scales of physical and role functioning (PF and RP), general health (GH) and mental health (MH), patients in both groups had significantly lower scores before the RT than in the comparison groups. After the procedures, there was a significant deterioration in the RP scale in Group 1 (18.75 vs. 40.00, pt < 0.05), and an improvement of almost 2 times in Group 2 (35.73 vs. 68.33, pt < 0.06). The indicator of general health (GH) at the end of RT in Group 1 did not change, and in Group 2 it tended to improve (20.93 vs. 47.26, pt < 0.06). Life expectancy (LE) in Group 1 tended to decrease further after treatment, having increased 1.7 times in Group 2. The study showed that cancer patients before the onset of RT experienced a rather strong distress and level of anxiety. Psychological correction of the emotional state at the beginning of treatment allowed for a significant improvement in the QOL of patients on the scales of role physical functioning (RF) and vitality (VT). An important area of work of a clinical psychologist at this stage of treatment involved correction of cognitive sphere, support of role functioning and formation of behavior aimed at further treatment.

Radiation and Checkpoint Inhibition Amongst HCC Patients With Portal Vein Invasion

<h3>Purpose/Objective(s)</h3> Recent studies established atezolizumab and bevacizumab as a new standard of care for Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC) stage C patients. However, many patients are not candidates for this combination and progression-free survival was only 6.8 months, suggesting that local therapy might be beneficial. This study explores combination radiotherapy and nivolumab for HCC with portal vein thrombus (PVT). <h3>Materials/Methods</h3> We retrospectively reviewed charts of patients with HCC and PVT treated with nivolumab and radiation at a single institution from 2016-2020. Patients were eligible if they had at least one follow up imaging scan to assess response. Progression-free survival (PFS) and overall survival (OS) were assessed. Baseline characteristics were used to predict for outcomes. <h3>Results</h3> 64 patients met inclusion criteria with a median follow up of 7 months (0.13-39.0 months). 42 (65.6%) patients were <b>de novo</b> diagnoses of HCC with PVT, and the remainder had prior therapy. 37 (57.8%) patients received nivolumab prior or concurrent with start of RT, while 27 (42.2%) received the first dose of nivolumab > 1 month post RT. Median radiation dose was 40 Gy (range: 30-50 Gy) with 44 (68.8%) patients being treated with SBRT<b>.</b> Median PFS was 3.8 months (95% confidence interval: 2.3–5.4). Median OS was 9.6 months (95% confidence interval: 5.2–14.0). On log-rank analysis, median OS and PFS did not differ between patients receiving therapy for a <b>de novo</b> diagnosis vs. previous therapy (OS: 12.9 vs 8.7 months, <i>P</i> = 0.46; PFS: 4.9 vs 2.9 months, <i>P</i> = 0.99), between patients with VP1-2 vs. VP3+ PVT (OS: 18.3 vs 9.4 months, <i>P</i> = 0.53; PFS: 3.3 vs 3.8 months, <i>P</i> = 0.44), between patients receiving SBRT vs. fractionated RT (OS: 9.2 vs 14.5 months, <i>P</i> = 0.69; PFS: 4.2 vs 3.2 months, <i>P</i> = 0.30), and between patients receiving nivolumab before/concurrent with RT vs. patients receiving nivolumab after RT (OS: 10.7 vs 9.6 months <i>P</i> = 0.41; PFS: 4.2 vs 2.9 months, <i>P</i> = 0.73). Patients with HCV trended for better OS than those with other etiologies but PFS was not improved (OS: 33.3 vs 8.7 months, <i>P</i> = 0.064; PFS: 4.8 vs 2.8 months, <i>P</i> = 0.16). 8 (12.5%) of the patients had OS times > 2 years. <h3>Conclusion</h3> In this retrospective series, combination nivolumab and radiation produced promising OS and PFS for HCC patients with PVT. Prospective studies are needed to know when this approach might be beneficial in the evolving landscape of immunotherapy in HCC.