Late Toxicity In Patients Research Articles

Conditional Risk and Predictive Factors Associated With Late Toxicity in Patients With Prostate Cancer Treated With External Beam Radiation Therapy Alone in the Randomized Trial RTOG 0126

The objective of this study was to characterize the conditional risk of developing grade 2+ urinary or gastrointestinal (GI) toxicity for patients treated with external beam radiation therapy in Radiation Therapy Oncology Group 0126. A secondary objective was to analyze baseline patient and treatment characteristics and determine their relevance in predicting toxicity both at the time of trial enrollment and at later points of follow-up. One thousand five hundred thirty-two patients with localized prostate cancer were enrolled between March 2002 and August 2008, of whom 1499 were eligible and included in data analysis with a median follow-up of 8.4 years (range, 0.02-13 years). Patients were treated with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy according to institutional practice without the addition of androgen deprivation and randomized to receive either standard-dose radiation therapy of 70.2 Gy or dose-escalated radiation therapy of 79.2 Gy of radiation therapy to the prostate only with standard fractionation. Univariate and multivariate analyses were performed to determine whether initial factors were predictive of late toxicity at the time of treatment and at later time points. As patients proceed further from completion of radiation therapy without the development of toxicity, the subsequent risk of both grade 2+ genitourinary (GU) and GI toxicity decreases with time. At the time of enrollment, the risk of developing grade 2+ toxicity over the next 5 years was 9.57% and 17.89%, respectively. After 5 years of toxicity-free survival, the risk of developing grade 2+ GU or GI toxicity in the subsequent 5 years was 3.02% and 1.54%, respectively. Baseline treatment and patient-related factors predicted late toxicity both at trial enrollment and after 2 years of toxicity-free survivorship. Baseline urinary dysfunction and dose-escalated radiation therapy were associated with increased late GU toxicity. Acute GI toxicity and dose-escalated radiation therapy were associated with increased risk of late GI toxicity. Treatment with intensity-modulated radiation therapy was associated with reduced risk of either toxicity. The conditional risk of grade 2+ toxicities decreases as patients proceed further from treatment, with most toxicities occurring in the first few years after treatment completion. Baseline patient and treatment characteristics remain relevant at both enrollment and later time points.

Acute and Late Toxicities in Patients with Collagen Vascular Disease Receiving Curative-Intent Intensity-Modulated Radiotherapy to the Head and Neck Region

Historically, collagen vascular disease (CVD) was considered at least a relative contraindication to radiotherapy (RT). However, more recent meta-analyses suggest that for patients with certain CVDs such as rheumatoid arthritis (RA), there may not be an increased risk for severe toxicities, while for patients with CVDs such as systemic lupus erythematosus (SLE), dermatomyositis (DM) and scleroderma, there may be as high as a 2- to 4-fold risk for severe toxicities compared to patients without CVD. There are also data to suggest that patients with head and neck cancer (HNC) and comorbid CVD are at especially high risk of severe toxicities from RT. This study evaluated the hypothesis that among patients with HNC treated with curative-intent intensity-modulated radiation therapy (IMRT), patients with SLE or DM were more likely to have had late grade ≥3 toxicity rates compared to patients with other CVDs. A total of 23 patients who had HNC with comorbid CVD and received IMRT between 2005-2022 were included. Acute (≤90 days after completion of RT) and late (>90 days) toxicities were retrospectively classified using CTCAE v5.0. Toxicity rates were compared across CVD groups using Chi-squared tests. Median follow-up was 56.3 months. The most common CVDs were RA (9 patients, 39%), SLE (4 patients, 17%), and DM (4 patients, 17%). Median total RT dose was 66 Gy (range: 48-70 Gy), in 1.8-2.4 Gy fractions. Nine (39%) patients received concurrent chemotherapy. 14 (61%) patients had mucosal squamous cell carcinoma (SCC), 3 (13%) had cutaneous SCC, 2 (9%) had nasal cavity/paranasal sinus tumors, 2 (9%) had salivary gland tumors, 1 (4%) had cutaneous melanoma, and 1 (4%) had mucosal melanoma. Eight (35%) patients experienced acute grade ≥3 toxicities, and 3 (13%) patients experienced late grade ≥3 toxicities (Table 1). No patients had grade≥4 toxicities. Patients with SLE or DM did not have significantly higher risk of late grade ≥3 toxicities compared to those with other CVDs (25% vs. 7%, p = 0.21). In this small sample size of patients with HNC and comorbid CVD, definitive or post-operative IMRT was associated with approximately 35% acute and 15% late severe toxicity rates. While SLE/DM were associated with >3-fold late grade ≥3 toxicities, this association needs to be confirmed with larger data sets.

Locoregional control and toxicity following high-dose hypofractionated and accelerated palliative radiotherapy regimens in breast cancer

AimsFor patients with locally advanced primary/recurrent breast cancer, radiotherapy is an effective treatment for locoregional control. 36 Gy in 6 Gy once-weekly fractions is a commonly used schedule, but there are no data comparing local control and toxicity between 36 Gy delivered once-weekly versus accelerated schedules of multiple 6 Gy fractions per week. This retrospective study compared local control rates and acute and late toxicity in patients undergoing 30–36 Gy in 6 Gy fractions over 6 weeks versus more accelerated schedules over 2–3 weeks for an unresected breast cancer. Materials and methodsPatients who received 30–36 Gy in 6 Gy fractions to an unresected breast cancer ± involved lymph nodes between December 2011 and August 2020 were identified. Patients were grouped into once-weekly versus accelerated fractionation schedules. Response rates, local control and toxicity data were analysed. ResultsIn total, 109 patients were identified. The median follow-up duration was 46 months. Forty-seven patients (43%) received once-weekly fractions and 62 patients (57%) received accelerated fractionation schedules. There were no significant differences in baseline tumour characteristics between the groups. Eighty-seven per cent of patients had an objective (complete or partial) response (81% in the once-weekly group; 91% in the accelerated group). The median time to local progression was 23.5 months overall (95% confidence interval 17.8–29.2); 23.5 months (95% confidence interval 18.8–28.1) in the once-weekly group and 19.0 months (95% confidence interval 7.0–31.1) in the accelerated group (P = 0.99). Acute toxicity of any grade occurred in 75% of patients (76% in the once-weekly group; 74% in the accelerated group) and grade 3 toxicity occurred in 7% of patients (7% in the once-weekly group; 8% in the accelerated group). There were no associations between the groups and acute or late toxicity grade (P = 0.78 and P = 0.26, respectively), although one grade 4 late toxicity (skin radionecrosis) occurred in a patient who received five fractions a week and therefore this regimen is not recommended. Study limitations included a lack of statistical power analysis, the necessary grouping of all accelerated patients for analysis and a high rate of censored data. ConclusionThere were no apparent differences in response rate, time to local progression or toxicity between patients who received 30–36 Gy in 6 Gy fractions once-weekly compared with twice-weekly as palliative treatment for locally advanced breast cancer. This regimen appears to be a safe alternative and may be preferred by patients.

Supportive care among head and neck cancer patients: An initial validation of the Dutch version of the Performance Status Scale for Head and Neck Cancer (D-PSS-HN).

Acute and late toxicities in patients treated with (chemo)radiotherapy for head and neck cancer (HNC) is common and can negatively impact quality of life and performance. Performance status instruments measure the functional ability to perform daily life activities and are important tools in the oncologic population. Since Dutch performance status scales for the HNC population are lacking, we conducted this study to translate the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) into Dutch (D-PSS-HN) and to validate this version. The D-PSS-HN was translated into Dutch according to the internationally described cross-cultural adaptation process. It was administered to HNC patients and together with the Functional Oral Intake Scale completed by a speech and language pathologist at five different time points during the first 5 weeks of (chemo)radiotherapy. Patients were asked each time to complete the Functional Assessment of Cancer Therapy and the Swallowing Quality of Life Questionnaire. Pearson correlation coefficients were used to calculate convergent and discriminant validity and the evolution of D-PSS-HN scores was assessed by means of linear mixed models. A total of 35 patients were recruited and > 98% of the clinician-rated scales were completed. Convergent and discriminant validity were demonstrated, with all correlations rs between 0.467 and 0.819, and between 0.132 and 0.256, respectively. The subscales of the D-PSS-HN are sensitive to detect changes through time. The D-PSS-HN is a valid and reliable instrument to assess performance status in patients with HNC treated with (chemo)radiotherapy. It is a useful tool to measure HNC patients' current diet level and functional abilities to perform daily life activities. What is already known on the subject Acute and late toxicities in patients treated with (chemo)radiotherapy for HNC are common and can negatively impact quality of life and performance. Performance status instruments measure the functional ability to perform daily life activities and are important tools in the oncologic population. However, Dutch performance status scales for the HNC population are lacking. Therefore, we translated the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) into Dutch (D-PSS-HN) and validated this version. What this paper adds to existing knowledge We translated the PSS-HN and demonstrated its convergent and discriminant validity. The subscales of the D-PSS-HN are sensitive to detect changes through time. What are the potential or actual clinical implications of this work? The D-PSS-HN is a useful tool to measure HNC patients' functional abilities to perform daily life activities. The tool can easily be used in clinical settings: since data collection duration is very short, this facilitates clinical (and research-related) implementation of the scale. Patients' individual needs could be identified by using the D-PSS-HN, resulting in more appropriate approaches and (early) referrals if needed. Interdisciplinary communication could be facilitated.

Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer

Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival. Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation. Statistical models were used to test associations between clinical characteristics and outcomes, including upper GI bleeding, radiation treatment breaks, and weight loss during therapy. Between 1999 and 2012, 211 patients were treated with radiation for pancreatic cancer. All patients received concurrent chemotherapy with either gemcitabine (174) or 5-fluorouracil (27), and 67 received intensity modulated radiation therapy (IMRT). Overall, 18 patients experienced an upper GI bleed related to treatment, with 70% of bleeds occurring in the stomach or duodenum, and among those patients, 11 (61%) patients had a pancreatic head tumor and 17 (94%) patients had a metallic biliary stent. IMRT was associated with decreased risk of postradiation nausea (odds ratio, 0.27 [0.11, 0.67], P=.006) compared with 3-dimensional conformal radiation. Regarding long-term toxicities, patients with a metallic biliary stent at the time of radiation therapy were at a significantly higher risk of developing upper GI bleeding (unadjusted hazard ratio [HR], 15.41 [2.02, 117.42], P=.008), even after controlling for radiation treatment modality and prescribed radiation dose (adjusted HR, 17.38 [2.26, 133.58], P=.006). Furthermore, biliary stent placement was associated with a higher risk of death (HR, 1.99 [1.41, 2.83], P < .001) after adjusting for demographic, treatment-related, and patient-related variables. Metallic biliary stents may be associated with an increased risk of upper GI bleeding and mortality. Furthermore, IMRT was associated with less nausea and short-term toxicity compared with 3-dimensional conformal therapy.

Impact of dose escalation on colostomy-free survival and treatment outcome in squamous cell anal carcinoma

PurposePrimary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer.MethodsConsidered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).ResultsThe 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3‑year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3‑year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3‑year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3‑year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067).ConclusionDose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.

Kent Oncology Centre Early Experience in the use of Biodegradable Pre-rectal Hydrogel in External Beam Radiotherapy or Brachytherapy

Purpose: To assess early and late toxicities in patients who had external beam radiotherapy (EBRT) or brachytherapy (BT) following biodegradable pre-rectal hydrogel (SpaceOAR) insertion at Kent Oncology Centre between May 2018 and January 2021.

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer

BackgroundThis study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy. Materials and MethodsPatients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea). ResultsIn total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break. ConclusionStatistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Patient-Reported Symptoms of Late Toxicity in Patients With Breast Cancer Treated With Hypofractionated Radiation Therapy and the Association With Quality of Life

Our purpose was to assess the prevalence of patient-reported symptoms of local late toxicity in patients with irradiated breast cancer and determine the association between late toxicity and quality of life. Within the prospective Utrecht cohort for Multiple BReast cancer intErvention studies and Long-term evaluation cohort, a survey on self-reported late toxicity was sent to all patients with breast cancer with ≥12 months interval since radiation therapy treated with curative intent. Patients were treated with hypofractionated radiation therapy of 40 Gy/15 fractions or 42.5 Gy/16 fractions, with or without a simultaneous integrated boost. Symptoms of late toxicity were evaluated on a 4-point Likert scale. Late toxicity was defined as moderate-severe breast or chest wall pain combined with at least 1 other mild-severe late toxicity symptom, that is, breast or arm/hand lymphedema, firmness of the breast, or impaired arm movement. Physical, role, and social functioning were measured before, during, and after the late toxicity survey using the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire-C30 and compared with a Dutch normative population. In the study, 1613/2248 patients (72%) were included. Of those, 16% (n=265) reported late toxicity. The median time interval between radiation therapy and survey was 38 months (interquartile range, 21-55). Moderate/severe firmness of the breast, chest wall pain, and breast pain were reported by, respectively, 18% (n=295), 14% (n=225), and 10% (n=140) of all patients. Physical, role, and social functioning were below the clinical threshold (ie, clinically relevant impairment) in 13% to 52% of patients with late toxicity and 2% to 26% of patients without late toxicity. Patients with late toxicity significantly more often received analgesics, physiotherapy, and lymphedema therapy compared with patients without late toxicity. This study provided insight into the prevalence of patient-reported late toxicity after hypofractionated radiation therapy and the influence of late toxicity on quality of life after breast cancer. These results may help health care professionals to inform their patients about long-term effects of breast cancer treatment including hypofractionated radiation therapy.

Toxicity Management in the Era of Changing Treatment Paradigms for Locally Advanced Rectal Cancer.

Treatment paradigms for locally advanced rectal cancer have evolved over the last several decades. Patients now have several different "standard" options with different radiation courses, sequencing of treatment modality and in some scenarios potentially avoidance of surgery. In this context, an updated understanding of treatment toxicity is needed to help patients make informed decision regarding their treatment. The RAPIDO study showed no difference in cumulative rate or grade of toxicity between short and long course radiation. Based upon our experience, patients with short course radiation tend to present with acute symptoms 1-2weeks after completion of radiation, while those receiving long course chemoradiation have symptoms towards the end of treatment. Treatments that may be helpful particularly for short course radiation toxicity include Bentyl (dicycloverine) and steroids. The most common toxicities from radiation are due to bowel and rectal inflammation leading to diarrhea, cramping, and urgency. The combination of surgery and radiation can exacerbate these symptoms. The most common late toxicity in patients receiving doublet chemotherapy is neurotoxicity. Rates of infertility differ in men versus women; all efforts for fertility preservation should be completed prior to initiation of any therapy.

No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity

Our aim was to test whether updated polygenic risk scores (PRS) for susceptibility to cancer affect risk of radiation therapy toxicity. Analyses included 9,717 patients with breast (n=3,078), prostate (n=5,748) or lung (n=891) cancer from Radiogenomics and REQUITE Consortia cohorts. Patients underwent potentially curative radiation therapy and were assessed prospectively for toxicity. Germline genotyping involved genome-wide single nucleotide polymorphism (SNP) arrays with nontyped SNPs imputed. PRS for each cancer were generated by summing literature-identified cancer susceptibility risk alleles: 352 breast, 136 prostate, and 24 lung. Weighted PRS were generated using log odds ratio (ORs) for cancer susceptibility. Standardized total average toxicity (STAT) scores at 2 and 5 years (breast, prostate) or 6 to 12 months (lung) quantified toxicity. Primary analysis tested late STAT, secondary analyses investigated acute STAT, and individual endpoints and SNPs using multivariable regression. Increasing PRS did not increase risk of late toxicity in patients with breast (OR, 1.000; 95% confidence interval [CI], 0.997-1.002), prostate (OR, 0.99; 95% CI, 0.98-1.00; weighted PRS OR, 0.93; 95% CI, 0.83-1.03), or lung (OR, 0.93; 95% CI, 0.87-1.00; weighted PRS OR, 0.68; 95% CI, 0.45-1.03) cancer. Similar results were seen for acute toxicity. Secondary analyses identified rs138944387 associated with breast pain (OR, 3.05; 95% CI, 1.86-5.01; P = 1.09 × 10-5) and rs17513613 with breast edema (OR, 0.94; 95% CI, 0.92-0.97; P = 1.08 × 10-5). Patients with increased polygenic predisposition to breast, prostate, or lung cancer can safely undergo radiation therapy with no anticipated excess toxicity risk. Some individual SNPs increase the likelihood of a specific toxicity endpoint, warranting validation in independent cohorts and functional studies to elucidate biologic mechanisms.

Quality of life and late toxicity after short-course radiotherapy followed by chemotherapy or chemoradiotherapy for locally advanced rectal cancer – The RAPIDO trial

Background and purposeThe RAPIDO trial demonstrated a decrease in disease-related treatment failure (DrTF) and an increase in pathological complete responses (pCR) in locally advanced rectal cancer (LARC) patients receiving total neoadjuvant treatment (TNT) compared to conventional chemoradiotherapy. This study examines health-related quality of life (HRQL), bowel function, and late toxicity in patients in the trial. Materials and methodsPatients were randomized between short-course radiotherapy followed by pre-operative chemotherapy (EXP), or chemoradiotherapy and optional post-operative chemotherapy (STD). The STD group was divided into patients who did (STD+) and did not (STD−) receive post-operative chemotherapy. Three years after surgery patients received HRQL (EORTC QLQ-C30, QLQ-CR29 and QLQ-CIPN20) and LARS questionnaires. Patients who experienced a DrTF event before the toxicity assessments (6, 12, 24, or 36 months) were excluded from analyses. ResultsOf 574 eligible patients, 495 questionnaires were returned (86%) and 453 analyzed (79% completed within time limits). No significant differences were observed between the groups regarding QLQ-C30, QLQ-CR29 or LARS scores. Sensory-related symptoms occurred significantly more often in the EXP group compared to all STD patients, but not compared to STD+ patients. Any toxicity of any grade and grade ≥ 3 toxicity was comparable between the EXP and STD groups at all time-points. Neurotoxicity grade 1–2 occurred significantly more often in the EXP and STD+ group at all time-points compared to the STD− group. ConclusionThe results demonstrate that TNT for LARC, yielding improved DrTF and pCRs, does not compromise HRQL, bowel functional or results in more grade ≥3 toxicity compared to standard chemoradiotherapy at three years after surgery in DrTF-free patients.

Can we treat with radiation breast cancer patients with covid-19 infection? Results from a prospective study

PurposeThe coronavirus disease 2019 (covid-19) caused by the severe acute respiratory syndrome coronavirus 2 (Sars-Cov-2) is at the origin of a global pandemic. This pandemic has prompted the current health system to reorganize and rethink the care offered by health establishments. We report the early and late toxicity in patients infected with covid-19 treated at the same time for early-stage breast cancer. Material and methodsThis is a monocentric prospective study of patients treated in our hospital between March and June 2020 who were diagnosed with covid-19 infection. The inclusion criteria were to be irradiated for early-stage breast cancer and to have a positive covid diagnosis on a polymerase chain reaction (PCR) test and/or a lung computed tomography (CT) scan and/or suggestive clinical symptoms. All of them needed 6 months follow-up clinic after the end of the radiotherapy with clinical examination, mammogram, as well as CT scan to evaluate the lung status. Radiotherapy consisted of breast or chest wall irradiation with or without lymph node irradiation, with protocols adapted to pandemic situation. The treatment-related toxicity was graded according to the Common Toxicology Criteria for Adverse Events (version 4.03). ResultsAll 350 patients treated for early-stage breast cancer were studied. Of them, 16 presented clinical symptoms of covid-19 infection, and of them 12 had clinical, CT scan and PCR confirmation. This entire cohort of 12 patients with median age of 56years (range: 42–72 years) underwent their radiotherapy. During the radiotherapy, nine patients presented radiodermatitis: eight grade 1 (66%) and one grade 2 (8%). Two patients with lymph nodes irradiation presented grade 2 oesophagitis. Late toxicity was evaluated 6 months after the end of the radiotherapy, and there was no radiation or covid lung sequel on the CT scans. One patient presented covid-related dyspnoea, and two had fibrosis. ConclusionThe half-year follow-up of prospective covid-19 cohort, treated for early-stage breast cancer demonstrated an acceptable toxicity profile with few low-grade adverse events. It seems that the covid-19 infection does not appear to increase the side effects of radiotherapy. Therefore radiotherapy should not be delayed.

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience.

BackgroundModerately post-operative hypofractionated radiotherapy (HYPO-RT) for breast cancer is a safe and effective strategy as seen in large prospective trials. This study aimed to assess overall and disease-free survivals, local control, and acute and late toxicities in patients treated with HYPO-RT.Materials and methodsData from patients submitted to post-operative HYPO-RT, with or without boost, were evaluated retrospectively. Demographic, disease, and treatment characteristics were collected.ResultsFrom March 2009 to December 2016, 393 patients were treated. Breast-conserving surgery was performed in 94.7%, immediate reconstruction after mastectomy in 6 (1.5%). Most patients (91.2%) had initial stage (0 to IIA), and chemotherapy was performed in 42.0%, HYPO-RT was mainly performed in 15 or 16 daily fractions of 267 cGy and 265 cGy, respectively. The median follow-up was 5.7 years. There were 25 deaths (6.4%) and 17 (4.3%) local recurrences. At 5 and 10 years, the overall survival, local control, and disease-free survival were, respectively, 96.0% and 79.3%, 99.2% and 94.9%, 96.6%, and 91.9%. Acute grade 3 or 4 dermatitis was observed in 0.9%. Late grade 1 or 2 occurred in less than 3% of the patients.ConclusionHYPO-RT is a safe and effective radiotherapy regimen with excellent disease control and overall survival rates, with low acute and late toxicity rates.

Assessment of Side Effects of Radiation Therapy in Patients With COVID-19 Treated for Early-Stage Breast Cancer

Purpose/Objective(s)The Covid-19 caused by the SARS-COV-2 coronavirus is at the origin of a global pandemic. This pandemic has prompted the current health system to reorganize and rethink the care offered by health establishments. We report the early and late toxicity in patients infected with COVID-19 treated at the same time for early-stage breast cancer (BC) toxicity.Materials/MethodsThis is a monocentric prospective study of patients treated in our hospital between March and June 2020. The monocentric registry was created for all cancer patients who were diagnosed with COVID 19 infection. The inclusion criteria of the patients evaluated were to be irradiated for early-stage breast cancer and to have a positive COVID diagnosis on a PCR test and / or a lung computed tomography (CT) scan and / or suggestive clinical symptoms. All of them needed 6 months follow up clinic after the end of the radiotherapy with clinical examination, mammogram, as well as CT scan to evaluate the lung status. Radiotherapy (RT) consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation, as well as hypofractionated schemes adapted to pandemic situation. The treatment-related toxicity was graded according to the CTCAE (version 4.03).ResultsThree hundred fifty patients (pts) have been treated for early-stage BC in our Department between 03/2017 and 06/2020. Of them, 16 were presented with clinical symptoms of COVID 19 infection and of them 12 had clinical, CT scan and PCR confirmation. This entire cohort of 12 pts with median age of 56 (42-72) underwent their RT. All patients were invited to realize CT scan 6 months after the end of RT and to come in the hospital for clinical and radiological evaluation. During the radiotherapy, there were 9 pts presented radio dermatitis, of the 8 (66%): grade 1 and one (8%) grade 2. Two patients treated to the regional lymph nodes presented esophagitis de grade 2. The late toxicity as well as the lung radiological evaluation was realized 6 months after the end of the radiotherapy and there was no RT or COVID lung sequel on the CT scans. There was one patient who presented COVID related dyspnea, and 2 patients with post treatment fibrosis.ConclusionThe half-year follow-up of prospective COVID19+ cohort, treated for early-stage BC demonstrated an acceptable toxicity profile with few low-grade adverse events. It seems that the COVID 19 infection does not appear to increase the side effects of RT. Therefore, the RT should not be delayed.

Toxicity Outcomes of Hypofractionated Image Guided Pencil Beam Scanning Proton Beam Therapy for Spinal Chordomas

To evaluate acute and late toxicities in patients of chordoma treated with hypofractionated, image guided pencil beam scanning proton beam therapy.Consecutive patients diagnosed with spinal chordomas treated at our center with pencil beam scanning proton beam therapy (part of a prospective SCCORE- Sarcoma, Chordoma, Chondrosarcoma registry) were included in this study. Among all patients, high risk CTV (CTV-HR) was treated to a dose of 70.4CGE/32fractions and intermediate risk CTV (CTV-IR) was treated to a dose of 57.6-64CGE/32fractions. Patients underwent clinical, radiological (including metabolic- DCE MRI imaging) and QOL (EORTC QOL QC-30) evaluations at baseline and 6 monthly thereafter. Acute and late toxicities were recorded at each clinical visit as per CTCAE V4.0 and LENT SOMA scales respectively. Clinical and radiological outcomes are being reported in this study.Consecutive 23 patients with a median age of 38 years (range 4-64 years) with histologically proven chordoma (20 classical chordomas, 1 chondroid chordomas and 2 de-differentiated chordomas were analyzed. Among patients with skull base and dorsal chordomas (15 patients) all patients underwent surgery at least once, 21% underwent surgery twice, 14% underwent thrice and 7% underwent more than 3 times. Among patients with sacral chordomas (8 patients), 63% underwent surgery at least once and 50% underwent more than once. 17% patients (2 clival and 2 sacral) underwent prior radiation with photons (IMRT technique) with 13% receiving more than once. Mean volumes of CTV HR and for skull base chordomas was 32.4cc (0.83-132cc) and for sacral chordomas was 855cc (96.1-1740cc). Two patients had acute grade 3 dermatitis, 1 patient had acute grade 3 oropharyngeal mucositis and 1 patient had acute grade 3 gastrointestinal mucositis. 28.5% of patients with Clival and 50% of patients with Sacral lesions had grade 2 acute toxicities. 1 patient had late grade 3 toxicity requiring tracheostomy. None of patients had any late grade 2/3 gastrointestinal or genitourinary toxicities. With a median follow up of 17 months (9-23 months), 21 patients (91%) remained radiologically stable with favorable metabolic response in all the 10 patients (43%) where metabolic imaging was available. Only 1 patient had in-field radiological progression and 1 patient had distant bone metastases.Pencil beam scanning proton beam therapy is feasible in patients with spinal chordomas. Despite high doses, large treatment volumes and large number of patients receiving prior treatments, the acute and late toxicities were relatively low in this cohort.

1586P Assessment of side effects of radiation therapy in patients with COVID-19 treated for early-stage breast cancer

The COVID-19 caused by the SARS-COV-2 coronavirus is at the origin of a global pandemic. We report the early and late toxicity in patients infected with COVID-19 treated at the same time for early-stage breast cancer (BC) toxicity. This is a monocentric prospective study of patients treated in our hospital between March and June 2020. The monocentric registry was created for all cancer patients who were diagnosed with COVID-19 infection. The inclusion criteria of the patients evaluated were to be irradiated for early-stage breast cancer and to have a positive COVID-19 diagnosis on a PCR test and / or a lung computed tomography (CT) scan and / or suggestive clinical symptoms. All of them needed 6 months follow up clinic after the end of the radiotherapy with clinical examination, as well as CT scan to evaluate the lung status. Radiotherapy (RT) consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation, as well as hypofractionated schemes adapted to the pandemic situation. The treatment-related toxicity was graded according to the CTCAE. Three hundred fifty patients (pts) have been treated for early-stage BC in our department. Of them, 16 were presented with clinical symptoms of COVID-19 infection and of them 12 had clinical, CT scan and PCR confirmation. This entire cohort of 12 pts with median age of 56 (42-72) underwent their RT. All patients were invited to realize CT scan 6 months after the end of RT and to come in the hospital for clinical and radiological evaluation. During the radiotherapy, 9 pts presented with radio dermatitis, of these 8 (66%) grade 1 and one (8%) grade 2. Two patients treated to the regional lymph nodes presented grade 2 esophagitis. The late toxicity as well as the lung radiological evaluation was realized 6 months after the end of the radiotherapy and there was no RT or COVID lung sequel on the CT scans. There was one patient who presented COVID-related dyspnea, and 2 patients with post-treatment fibrosis. The half-year follow-up of prospective COVID-19+ cohort, treated for early-stage BC demonstrated an acceptable toxicity profile with few low-grade adverse events. It seems that the COVID-19 infection does not appear to increase the side effects of RT. Therefore, the RT should not be delayed.

OC-0337 Quality of life, functional outcome and late toxicity in patients treated within the RAPIDO trial

OC-0337 Quality of life, functional outcome and late toxicity in patients treated within the RAPIDO trial

Intensity-modulated radiation therapy with concurrent chemotherapy for head and neck squamous cell carcinomas: Toxicity assessment

Background: Intensity-modulated radiotherapy with concurrent chemotherapy attempt to maintain efficiency while limiting toxicity in the treatment of neck squamous cell carcinomas. Side effects of the therapy are both challenge during treatment such as treatment delay, increasing financial and hospitalization rate and also cause early and late toxicities, affects to patient performances and treatment outcomes. We aimed to assess acute and late toxicity in patients with head and neck squamous cell carcinoma (HNSCC) managed with concurrent chemoradiation therapy using intensity modulated radiation therapy (IMRT) technique. Methods: A prospective descriptive study of 120 patients suffering from non-metastatic HNSCC received Intensity-modulated radiotherapy concurrently with four to six cycles of cisplatin (30mg/m2/day/ weekly) from May 2017 to 2018 at Hue Central Hospital (Vietnam). The dose to the primary tumour and cervical lymph nodes totally taken was 70 Gy. Toxicities were gradedbased on the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG). Results: Acute toxicities were mainly at grade 1 with oral mucositis, dermatitis and nausea/vomiting. For late toxicities, grade 3 xerostomia accountings for 5.8%. Neck fibrosis and trismus were not at grade 3 to grade 4, grade 1 mandibular bone necrosis (3.4%) was found in 3 patients. Conclusions: Concurrent chemoradiation therapy with IMRT demonstrated a well-tolerated regime with manageable toxicities.

Breast Conservation in Women with Autoimmune Disease: The Role of Active Autoimmune Disease and Hypofractionation on Acute and Late Toxicity in a Case-Controlled Series

Autoimmune connective tissue disease (CTD) has historically represented a relative contraindication to breast conservation (BC) among patients with early-stage breast cancer. Controversy exists regarding the use of hypofractionated radiation therapy (RT) among patients with CTDs. We evaluated acute and late toxicity in patients with breast cancer and CTD treated with BC. Of 1983 patients treated with BC from 2012 to 2016, we identified 91 patients with an autoimmune disease (AD). Each patient was matched to a control without AD based on age, RT field, and fractionation. RT toxicity and clinician-rated cosmesis were compared between cases and controls. Overall survival, disease-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier method. The median follow-up was 49.9 months for cases and 53.0 months for controls, and 67% of cases and controls were treated with hypofractionated RT. There was no difference in grade 2/3 acute toxicity between cases and controls (26.4% vs. 16.5%, respectively; P = .148). There was a significantly higher rate of grade 2/3 late toxicity among cases (25.8% vs 12.1% among controls; P = .049). Active AD at the time of RT increased the rate of grade 2/3 late toxicity compared with controls (41.7% in cases vs. 11.4% in controls; P = .018). Among patients treated with hypofractionated RT, there was no difference in acute or late grade 2/3 toxicity between cases and controls (acute: 13.1% in cases vs. 11.5% in controls [P > 0.9]; late: 11.9% in cases vs. 13.1% in controls [P > 0.9]). The rates of good/excellent clinician-rated cosmesis were similar between groups (92.9% in cases vs. 98.9% in controls; P = .142). In the largest matched case-control study of patients with CTD treated with conventional and hypofractionated RT, we demonstrate low rates of radiation toxicity, with good to excellent clinician-rated cosmesis. There was increased late toxicity in cases, especially in patients with active AD at time of RT. There was no increase in acute or late toxicity in the patients treated with hypofractionation.