Severe Late Toxicity Research Articles

Moderate hypofractionated post-prostatectomy radiation therapy is feasible and well tolerated: experience from a single tertiary cancer centre.

Conventional post-prostatectomy radiation therapy comprises 6.5-8weeks of treatment, therefore, hypofractionated and shortened schemes arouse increasing interest. We describe our experience regarding feasibility and clinical outcome of a post-prostatectomy moderate hypofractionated image-guided radiotherapy schedule MATERIALS AND METHODS: From Oct 2015-Mar 2020, 113 patients, median age of 62years-old (range 45-76) and prostate adenocarcinoma of low risk (30%), intermediate risk (49%) and high risk (21%) were included for adjuvant (34%) or salvage radiation therapy (66%) after radical prostatectomy (RP). All patients underwent radiotherapy with image-guided IMRT/VMAT to a total dose of 62.5Gy in 2.5Gy/fraction in 25 fractions. Sixteen patients (14%) received concomitant androgen deprivation therapy. With a median follow-up of 29months (range 3-60months) all patients but three are alive. Eleven patients (10%) developed exclusive biochemical relapse while 19 patients (17%) presented macroscopically visible relapse: prostatectomy bed in two patients (2%), pelvic lymph nodes in 13 patients (11.5%) and distant metastases in four patients (4%). The 3years actuarial rates for OS, bFRS, and DMFS were 99.1, 91.1 and 91.2%, respectively. Acute and late tolerance was satisfactory. Maximal acute genitourinary (AGU) toxicity was G2 in 8% of patients; maximal acute gastrointestinal (AGI) toxicity was G2 in 3.5% of patients; maximal late genitourinary (LGU) toxicity was G3 in 1% of patients and maximal late gastrointestinal (LGI) toxicity was G2 in 2% of patients. There were no cases of severe acute or late toxicity. No relationship was found between acute or late GI/GU adverse effects and dosimetric parameters, age, presence of comorbidities or concomitant treatments. Hypofractionated radiotherapy (62.5Gy in 25 2.5Gy fractions) is feasible and well tolerated with low complication rates allowing for a moderate dose-escalation that offers encouraging clinical results for biochemical control and survival in patients with prostate cancer after radical prostatectomy.

Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the \u2018TOaSTT\u2019 database

BackgroundMetastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients.MethodsA retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan–Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis.ResultsMDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30–3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05–2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10–3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09–5.89). Death was never therapy-related.ConclusionsMetastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation.Trial registration: retrospectively registered

The efficacy of iodine-125 interstitial brachytherapy for the treatment of locally advanced adenoid cystic carcinoma of the base of tongue: a non-surgical approach.

PurposeThe present study retrospectively evaluated the effectiveness and safety of iodine-125 interstitial brachytherapy for treatment of primary locally advanced adenoid cystic carcinoma (ACC) of the base of tongue (BOT).Material and methodsThis study was a retrospective analysis of data of 19 patients with ACC, who were treated with iodine-125 interstitial brachytherapy between March 2008 and April 2018. Overall survival (OS), disease-free survival (DFS), local control (LC), and radiation-related toxicities were determined. Factors affecting the outcomes were evaluated.ResultsSix males and 13 females were included in our study, with a median follow-up time of 35 months. 3- and 5-year OS rates were 71.5% and 47.6%, respectively. 3- and 5-year LC rates were 88.5% and 34.5%, respectively. 3- and 5-year DFS rates were 54.7% and 21.9%, respectively. A significant difference was observed in patients with or without brain metastases for OS rate. No severe acute toxicity was observed, while severe late toxicity was observed in one patient.ConclusionsThe results suggest that iodine-125 interstitial brachytherapy is an effective and safe option for the treatment of primary locally advanced ACC of the base of the tongue, with reasonably satisfactory LC and OS.

De-intensification strategies in HPV-related oropharyngeal squamous cell carcinoma-a narrative review.

Human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a relatively new clinical entity that is dramatically on the rise globally. HPV+ OPSCC is thought to be a separate clinical entity compared to HPV− OPSCC with a distinct tumor biology. Patients with HPV associated disease have been shown to have a substantially better prognosis and overall survival than those patients with the HPV negative (HPV−) counterpart. The standard of care for OPSCC is definitive radiation therapy (RT) and concurrent chemoradiation therapy (CRT), for lower and higher stage disease, respectively. However, traditional CRT is also associated with severe acute and late toxicities affecting patient quality of life, such as severe mucositis, dry mouth and dysphagia. Considering that HPV+ OPSCC is on the rise in a younger, healthier patient population and the good prognosis of HPV-related disease, there has been a focus on reducing treatment toxicities and optimizing quality of life while maintaining favorable oncologic outcomes. A variety of such de-escalation regimens are currently being explored in recently completed and ongoing clinical trials. Alterations to the standard chemotherapy, radiation and surgical regimens are being explored. This review will provide an overview of the rationale for and available results of the major de-intensification strategies in the treatment of locally advanced HPV+ OPSCC.

Clinical Predictors Of Severe Late Urinary Toxicity After Curative Intensity-Modulated Radiation Therapy For Localized Prostate Cancer

Clinical Predictors Of Severe Late Urinary Toxicity After Curative Intensity-Modulated Radiation Therapy For Localized Prostate Cancer

Toxicities after Hypofractionated Radiotherapy in Setting of Collagen Vascular Disease

Patients with collagen vascular disorders (CVD) have been regarded as contraindications for radiotherapy (RT) due to concerns of greater risks for late radiation effects. Recent reports have found toxicities between those with and without CVD to be similar using conventionally fractionated regimens. Hypofractionation is increasingly utilized for many indications, but there is hesitancy to use them for CVD patients since larger dose per fraction may compound late toxicity, despite lack of clinical evidence. We hypothesize that hypofractionation does not increase rates of toxicity in CVD patients. 249 treatments from 192 CVD patients from February 2007 to April 2019 at a single institution were retrospectively reviewed. CVD type, activity, and steroid use were evaluated. Dose per fraction, radiated site, planning target volume (PTV), and concurrent cancer therapies were also assessed. Toxicity ≤ 90 days from treatment was acute, and any after was late. Toxicity was graded by CTCAE version 5, and grade ≥ 3 was severe. Dose fractionation was defined as conventional (CF; 1.8-2Gy/fxn), moderate hypofractionated (MH; 2-5Gy/fxn), and ultra hypofractionated (UH; >5Gy/fxn). Fisher’s exact test and one-way analysis of variance (ANOVA) assessed differences in severe toxicity and PTV by fractionation groups, respectively. Uni- and multivariable logistic regression models identified prognostic variables for toxicity. Common CVDs were rheumatoid arthritis (37%), psoriasis (24%), and systemic lupus erythematosus (17%). 37%, 28%, and 35% of treatments were CF, MH, and UH, respectively. Median follow-up was 3 years. By fractionation groups, there were no significant differences in severe acute (5.4%, 7.3%, and 1.7%, p = 0.35) or late (8.3%, 0%, and 2.2%, p = 0.12) toxicities. Dose fractionation, radiated site, and multiple RT courses were significantly associated with late toxicity on multivariable analysis (Table). More specifically, MH (OR 0.32) and UH (OR 0.29) had lower odds for late toxicity compared to CF. Mean PTV was smaller with larger dose per fraction yet was not significantly different by fractionation groups (p = 0.18), nor associated with toxicity on multivariable analyses. Severe toxicity rates from MH or UH in CVD patients were not different from CF. MH and UH were associated with lower odds of developing late toxicity. Hypofractionation may be safe for CVD patients, though longer follow-up and additional patients with and without CVD are needed to further evaluate late toxicity.Abstract 2386; TableSignificant factors associated with toxicity on univariate and multivariable analysesUnivariate analysisAcute toxicityLate toxicityORp-valueORp-valueUH0.13< 0.001MH0.320.01UH0.29< 0.01Multivariable analysis--MH*0.200.02UH*0.19< 0.05Musculoskeletal radiated site0.030.01Multiple radiation courses7.360.03MH moderate hypofractionation; UH ultra-hypofractionation.*Relative to conventional fractionation. Relative to breast. Open table in a new tab

Excellent Local Control and Survivals after Particle Beam Radiation Therapy for Skull Base Malignancies

Complete resection of skull base malignancies (SBM) is challenging, and prognoses of patients with unresected or incompletely resected SBM is suboptimal. Radiotherapy (RT) plays a significant role in the treatment of SBM. Particle beam radiation therapy (PBRT), such as proton and carbon-ion radiotherapy (PRT and CIRT) demonstrates prominent advantages with its physical properties which enable improved dose coverage to the tumor target(s) and avoid overdosing to adjacent organs at risk thereby achieve optimal efficacy and safety. The purpose of this study is to report the clinical outcomes of intensity modulated PBRT for a relatively large group of patients with SBM. All patients with SBM (chordoma excluded due to its indolent behavior) treated at the Shanghai Proton and Heavy Ion Center from 06/2014 to 07/2019 were included in this analysis. The overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were calculated using the Kaplan-Meier method. Multivariate analyses (MVA) on survivals were performed using Cox proportional hazards model. Indicators used for MVA included age, sex, pathology, T-category, status of recurrence (post-RT or surgery), R0/1 vs. R2 resection, use of chemotherapy, and PBRT technology (PRT vs. CIRT vs. PRT+CIRT). Acute and late toxicities were assessed with the CTCAE (v. 4.03). Among the 176 consecutive patients with SBM (adenoid cystic carcinoma 53, soft tissue sarcoma 31, chondrosarcoma 29, squamous cell carcinoma 19, melanoma 12, adenocarcinoma 10, esthesioneuroblastoma 8, osteosarcoma 6, and other histologies 8) treated, 134 patients (76.1%) had locally advanced (T3/4) disease, 136 (77.3%) were radiation-naïve and 40 (22.7%) failed prior radiotherapy, and 134 (76.1%) received R2 resection before PBRT. Patients were treated with CIRT (n = 126) alone, PRT (n = 9) alone, or PRT+CIRT boost (n = 49). The median dose was 66 Gy (RBE). Chemotherapy was used in 20.5% of the patients. With median follow-up of 20.0 months, the 1-/2-year OS, LRFS, and DMFS, and PFS rates were 93.9/87.1%, 90.3/82.2%, 89.9/84.9%, and 66.1/46.6%, respectively. On MVA, age of ≥ 40 was associated with significantly worse OS (p = 0.05) and PFS (p = 0.02). Patients presented with failure after prior radiotherapy (p = 0.009) or surgery (p = 0.029) had significantly worse LRFS after PBRT. Additionally, higher T-classification (i.e., T3/T4) (p = 0.017) and recurrence after surgery (p = 0.06) was associated with significantly worse PFS (Table). Severe (≥ grade 3) acute toxicities included mucositis (n = 1), visual impairment (n = 2), and hemorrhage (n = 1). Severe late toxicities included oligosialia (n = 2), decreased vision (n = 2), osteonecrosis (n = 1), and hemorrhage (n = 1). PBRT provides effective disease control and survivals for SBM with favorable toxicity profiles. Further follow-up is needed to understand the long-term efficacy and safety.

Stereotactic Radiotherapy for Pancreatic Cancer: A Single-Institution Experience.

IntroductionDespite treatment advances, the prognosis of locally advanced pancreatic cancer is poor. Treatment remains varied and includes systemic and radiotherapy (RT). Stereotactic body radiotherapy (SBRT), highly conformal high-dose RT per fraction, is an emerging treatment option.Materials and methodsWe performed a single-institution retrospective review of patients with pancreatic adenocarcinoma treated with SBRT from 2015-2017. The median dose was 27 Gy (range: 21-36 Gy) in three fractions. Endpoints included local progression (RECIST 1.1; Response Evaluation Criteria in Solid Tumors 1.1), distant metastasis, overall survival, and toxicity.ResultsForty-one patients were treated, with a median follow-up of eight months. Patients who received SBRT had unresectable (49%), metastatic (17%), or borderline resectable (7%) disease, declined surgery (17%), medically inoperable (7%), or developed local recurrence following the Whipple procedure (2%). The six-month and one-year rates of local progression-free survival, distant metastasis-free survival, and overall survival were 62% and 55%, 44% and 32%, and 70% and 49%, respectively. Five patients (12%) experienced seven late gastrointestinal (GI) grade 3 events.Conclusion SBRT may be considered a treatment option to achieve local control of pancreatic cancer and is associated with a modest risk of severe late GI toxicities. Systemic therapies remain important, given the proportion of patients who develop distant metastases.

Dose-Response Model for Severe Late Laryngeal Toxicity after Stereotactic Body Radiation Therapy for Previously Irradiated Head and Neck Cancer

We sought to evaluate the association between larynx dose and risk of severe late laryngeal toxicity in patients undergoing re-irradiation SBRT for recurrent HNC. Fifty-five patients with an intact larynx underwent re-irradiation SBRT to a median dose of 44 Gy in 5 fractions. Five (41.7%) patients treated for a laryngeal/hypopharyngeal recurrence experienced late grade ≥3 laryngeal toxicity, compared to 0.0-7.1% for other sites. Logistic dose-response models were created to predict risk of severe late laryngeal toxicity, including dysphagia and airway compromise. According to the model, the risk of severe laryngeal toxicity with a larynx D5cc of 5 Gy is 5.8% (95% CI 2.9-9.9%) and rises to 11.4% with a D5cc of 20 Gy and 25.3% with a D5cc of 40 Gy. In patients with a laryngeal/hypopharyngeal recurrence, SBRT planning should carefully assess the dose to laryngeal structures given these dose findings, and SBRT should be approached with significant caution in such patients.

Evaluation of Preoperative Short Course Intensity Modulated Radiation Therapy in Treatment of Locally Advanced Rectal Carcinoma.

Background: The optimal RT fractionation and the timing of surgery in resectable locally advanced rectal carcinoma is still debatable. Postponing the time of surgery after SCRT seems to be more beneficial in inducing down-staging, and reducing postoperative morbidity than SCRT with immediate surgery. IMRT is used successfully in many cancers helping to achieve better conformality. Objectives: The study aimed to evaluate the efficacy and tolerability of preoperative short-course IMRT with delayed surgery in patients with resectable locally advanced rectal carcinoma. Patients and methods: Patients with resectable locally advanced rectal carcinoma were treated with preoperative short-course IMRT (25 Gy over 5 fractions) followed by surgery after 4-8 weeks. Results: 37 patients were included, down-staging was observed in 54.1% of them; patients with cN2 disease, radiological EMVI, and radiologically involved mesorectal facia (MRF) tend to have a statistically significant less down-staging. severe early and late toxicity was reported in 5.4% and 8.1% of the patients respectively, and 37 % had postoperative complications. 33 patients (94.6%) had curative surgery, 9% had pCR, and sphincter sparing was achieved in 28% of patients with low rectal tumors. Cumulative 2 years DFS and OS were 71 % and 80 % respectively. Conclusion: SCRT with delayed surgery is a valid convenient, safe, and economically beneficial option in the treatment of locally advanced resectable rectal carcinoma, utilization of IMRT can help in reducing the dose to organs at risk. Further studies with a larger number of patients are mandatory to identify the most suitable patients for this approach.

Normal Tissue Response of Combined Temporal and Spatial Fractionation in Proton Minibeam Radiation Therapy

Proton minibeam radiation therapy, a spatial fractionation concept, widens the therapeutic window. By reducing normal tissue toxicities, it allows a temporally fractionated regime with high daily doses. However, an array shift between daily fractions can affect the tissue-sparing effect by decreasing the total peak-to-valley dose ratio. Therefore, combining temporal fractions with spatial fractionation raises questions about the impact of daily applied dose modulations, reirradiation accuracies, and total dose modulations. Healthy mouse ear pinnae were irradiated with 4 daily fractions of 30 Gy mean dose, applying proton pencil minibeams (pMB) of Gaussian σ = 222 μm in 3 different schemes: a 16 pMB array with a center-to-center distance of 1.8 mm irradiated the same position in all sessions (FS1) or was shifted by 0.9 mm to never hit the previously irradiated tissue in each session (FS2), or a 64 pMB array with a center-to-center distance of 0.9 mm irradiated the same position in all sessions (FS3), resulting in the same total dose distribution as FS2. Reirradiation positioning and its accuracy were obtained from image guidance using the unique vessel structure of ears. Acute toxicities (swelling, erythema, and desquamation) were evaluated for 153 days after the first fraction. Late toxicities (fibrous tissue, inflammation) were analyzed on day153. Reirradiation of highly dose-modulated arrays at a positioning accuracy of 110 ± 52 μm induced the least severe acute and late toxicities. A shift of the same array in FS2 led to significantly inducted acute toxicities, a higher otitis score, and a slight increase in fibrous tissue. FS3 led to the strongest increase in acute and late toxicities. The highest normal-tissue sparing is achieved after accurate reirradiation of a highly dose modulated pMB array, although high positioning accuracies are challenging in a clinical environment. Nevertheless, the same integral dose applied in highly dose-modulated fractions is superior to low daily dose-modulated fractions.

A multicenter prospective phase II study of postoperative hypofractionated stereotactic body radiotherapy (SBRT) in the treatment of early-stage oropharyngeal and oral cavity cancers with high risk margins: the STEREO POSTOP GORTEC 2017-03 trial

BackgroundPrimary surgery is usually the mainstay treatment in early-stage oropharyngeal and oral cavity cancer. Typically, neck surgery is performed. Negative tumor margins are recommended (> 5 mm). If feasible, re-resection of any positive margin is preferred. Otherwise, postoperative radiotherapy is required. Adjuvant postoperative radiotherapy can be limited to the primary site for patients with pT1-T2 tumors and negative neck exploration. Currently, both fractionated external beam radiotherapy and brachytherapy can have a role in the postoperative management of early-stage oropharyngeal and oral cavity cancer with high risk margins. Another possible alternative could be postoperative stereotactic body radiotherapy (SBRT). The aim of this study is to evaluate postoperative SBRT in the treatment of early-stage oropharyngeal and oral cavity cancer with high risk margins.MethodsThe STEREO POSTOP study is a national, open-label, non-randomized phase II trial within the GORTEC network. Patients with early-stage oropharyngeal and oral cavity cancers with high risk margins indicating the need for postoperative radiation are eligible for enrollment. SBRT consists of a total dose of 36 Gy in 6 fractions over 2 weeks. The primary endpoint is severe late toxicity defined as 2-year toxicity of grade ≥ 3 according to CTCAE V4.03 classification. The secondary endpoints include acute toxicity (≤ 3 months), local and locoregional control, disease-free and overall survival, quality of life of patients, nutritional impact and predictive factors of toxicity. The experimental design chosen is a one-step Fleming plan design without interim analysis as the primary endpoint will be evaluated at a 2-year follow-up. Ninety patients will be recruited. The study was started in January 2018 with a 4-year enrollment period and an estimated completion in January 2024.DiscussionThis study is the first prospective trial to evaluate head and neck cancer postoperative SBRT in the setting of early-stage oropharyngeal and oral cavity cancers with high risk margins. SBRT is an attractive option because it delivers a highly conformal dose of radiation in a limited number of fractions (like brachytherapy but with less contraindication), with steep dose gradients resulting in reduced normal tissue irradiation and with a short overall treatment time.Trial registrationClinicaltrials.gov: NCT03401840, registered on 17-1-2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID - RCB 2017-A02058–45, registered on July 2017.Protocol version: Version 3 dated from 25th November 2019.

Intensity-Modulated Radiation Therapy for Esthesioneuroblastoma: 10-Year Experience of a Single Institute.

Objectives: To evaluate efficacy and safety of intensity-modulated radiotherapy (IMRT) in the management of esthesioneuroblastoma (ENB).Methods and Materials: A retrospectively analysis of 52 ENB patients treated with IMRT between 8/2008 and 8/2018 was performed. Thirteen of the 44 patients (29.5%) with newly diagnosed and 2 of the 8 patients with recurrent disease presented regional lymph node metastasis. The median dose of IMRT was 66 (range 52.5–75) Gy for all patients. Elective nodal irradiation (ENI) was provided to all excluding 6 patients in this cohort.Results: With a median follow-up time of 32.5 (6~121) months, the 3-year overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) rates for the entire cohort were 89.7, 69.5, 89.7, 95.1, and 85.4%, respectively. Multivariate analysis revealed that N-classification (N– vs. N+) at presentation was the only significant prognosticators for PFS. No significant prognosticator was identified for other survival outcome. No severe (i.e., grade 3 or 4) IMRT-induced acute toxicity was observed. Severe late toxicities were infrequent (11.5%), which included dysosmia (3.8%), hearing loss (3.8%), radiation brain injury (1.9%), and temporal lobe necrosis (1.9%). Moreover, late ocular toxicity secondary to IMRT was not observed.Conclusion: IMRT produced acceptable 3-year outcomes in terms of OS (89.7%), LPFS (89.7%), and RPFS (95.1%) rates without substantial late adverse effects. Further investigations for a more effective systemic strategy for distant disease control as well as a precision radiation technique for further improvement in local control are needed.

Efficacy and toxicity of postoperative external beam radiotherapy or chemoradiation for early-stage cervical cancer

ObjectiveThe aim of this study was to assess the impact of the evolving role of the addition of chemotherapy to postoperative radiotherapy on oncological outcomes and toxicity in patients with...

Overlapping volumes in re-irradiation for head and neck cancer \u2013 an important factor for patient selection

BackgroundThere is a lack of consensus concerning the definition of re-irradiation and re-irradiation volumes in head and neck cancer (HNC). The aim of the present study is to introduce a more strict definition of the re-irradiated volume that might better predict the risk of serious side-effects from treatment.MethodsFifty-four consecutive patients re-irradiated for HNC cancer were retrospectively analysed. CT images were deformably registered and the dose distributions accumulated after conversion to EQD2. Patients with a cumulative dose of ≥100 Gy in the overlapping volume (V100) were included in the study. Survival data and radiation-related acute and late toxicities were recorded.ResultsThe overall survival of all included patients at 2 and 5 years was 42.6 and 27.3% respectively and the progression free survival at 2 and 5 years was 32.5 and 28.5% respectively. The overall rate of any event of severe (grade ≥ 3) acute and late toxicity was 26 and 51%, respectively. We found that severe acute toxicity was more common in patients who had a larger overlapping volume (V100 > mean) where 43% of the patients experienced grade ≥ 3 acute toxicity, compared to the patients with smaller overlapping volumes (V100 < mean) where only 11% had severe toxicity (p = 0.02). The seemingly high rates of late toxicity in the present study could be due to the use of a more strict definition of re-irradiation. In previous studies also patients with low dose overlap are included and our results imply that there is a risk that previous studies might have overestimated the risk-benefit ratio in re-irradiation of HNC.ConclusionsOur study describes the outcome of a patient material where a more strict definition of the re-irradiated volume is used. With this definition, which could better describe the volume of highest risk for serious complications, we found that larger such overlapping volumes result in an increase in severe acute side-effects. A clear definition of re-irradiation and re-irradiation volumes is of utmost importance for future studies of HNC to make results from different studies comparable.

Multidisciplinary personalized approach in the management of vulvar cancer – the Vul.Can Team experience

IntroductionMultidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was...

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity.

Stereotactic body radiation therapy (SBRT) is considered an effective and safe treatment in patients with low- and intermediate-risk prostate cancer (PC). However, due to alack of long-term follow-up and late toxicity data, this treatment is not universally accepted. The present study aimed to evaluate outcome and early and late toxicity in acohort of patients with low- and intermediate-risk PC treated prospectively with linear accelerator (linac)-based SBRT. Patients with low- or intermediate-risk (NCCN criteria) PC were included. All patients received linac-based SBRT to 35 Gy in 5fractions delivered on alternate days. Endpoints were toxicity, biochemical relapse-free survival (BRFS), metastatic progression-free survival (mPFS), and overall survival (OS). From 2012 to 2018, 178 patients were treated. Median baseline prostate-specific antigen (iPSA) was 6.37 ng/ml (range 1.78-20). Previous transurethral resection of the prostate (TURP) was present in 23 (12.9%) patients. Median follow-up was 58.9 months (range 9.7-89.9). BRFS rates at 1, 3, and 5years were 98.3 (95% confidence interval, CI, 94.7-99.4%), 94.4 (95%CI 89.4-97), and 91.6% (95%CI 85.4-95.2), respectively. In univariate analysis, performance status (PS), iPSA, and nadir PSA (nPSA) were correlated with BRFS. In multivariable analysis iPSA and nPSA remained significant. BRFS rates at 5years were 94.9% (95%CI 86.8-98) for International Society of Urological Pathology (ISUP) grade group1, 93.2% (95%CI 80.5-97.7) for ISUP group2, and 74.8% (95%CI 47.1-89.5) for ISUP group3. At 1, 3, and 5years, mPFS rates were 98.8 (95%CI 95.5-99.7), 96.2 (95%CI 91.9-98.3), and 92.9% (95%CI 87.2-96.2), respectively; OS rates were 100, 97.2 (95%CI 92.9-98.9), and 95.1% (95%CI 90-97.6), respectively. One (0.56%) case of grade3 acute genitourinary (GU), one case of acute gastrointestinal (GI), and one case of grade3 late GU toxicity were observed. GI toxicity positively correlated with prostate volume. At long-term follow-up, linac-based SBRT continues to be avalid option for the management localized PC. Biochemical control remains high at 5years, albeit with some concerns regarding the optimal schedule for unfavorable intermediate-risk PC. Considering the excellent prognosis, patient selection is crucial for prevention of severe late toxicity.

Late gastrointestinal toxicity after radiotherapy for rectal cancer: a systematic review.

Although the multimodal cancer treatment techniques have greatly improved over the years, irradiation-induced late gastrointestinal toxicity remains a great concern as it may highly affect the quality of life of a patient. The aim of this study was to define the prevalence of late gastrointestinal toxicities. Electronic databases of Cochrane Library, Embase, Web of Science, CENTRAL and PubMed were searched until September 2019. We used the following keywords: radiotherapy, radiation therapy, irradiation, rectal cancer, gastrointestinal toxicity, adverse effects, late effects, pelvic radiation and pelvic radiation disease. Nine studies were included into this review out of 4785 that were preidentified as potentially relevant. Overall prevalence of severe (Grade 3 or higher) late irradiation-induced gastrointestinal toxicities was up to 19%. Most frequent toxicities of any grade were reported to be diarrhoea (up to 35%), faecal incontinence (22%), incontinence to gas (71%), rectal bleeding (9%), rectal pain (13%) and obstruction (7.4%). Preoperative treatment approaches and more advance radiotherapy techniques such as intensity-modulated and image-guided radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) turn out to result in lower late gastrointestinal toxicity rates. After great improvements in rectal cancer treatment, late gastrointestinal toxicity after radiotherapy is experienced less frequent and less severe; however, it remains a great concern associated with worse quality of life.

Preliminary study of intensity-modulated carbon ion reirradiation for locoregionally recurrent nasopharyngeal carcinoma after definitive IMRT——Clinical experience from Shanghai Proton Heavy Ion Hospital

Objective To evaluate the short-term efficacy and toxicities of intensity-modulated carbon ion radiotherapy (IMCT) for patients with locoregionally recurrent nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). Methods A total of 112 patients with locoregionally recurrent nasopharyngeal carcinoma undergoing salvaging IMCT between May 2015 and February 2018were enrolled in the study. All patients previously received one course of definitive X-ray IMRT. Among them, 10 patients (9%) were diagnosed with stage Ⅰ, 26 patients (23%) with stage Ⅱ, 41 patients (37%) with stage Ⅲ and 35 patients (31%) with stage Ⅳnasopharyngeal carcinoma, respectively. The median age of the cohort was 48 years (range, 17-70 years) old. The median dose to the gross tumor volume (GTV) was 60 GyE (range, 50-69 GyE). Results With a median follow-up time of 20 months (range, 5-45 months), 20 patients died and 42 patients developed local recurrence. The 2-year overall survival (OS) and local progression-free survival (LPFS) rates were 85% and 52%. Both univariate and multivariate analyses demonstrated that stage Ⅳ disease was associated with significantly worse OS. No predictors were found for LPFS. No acute toxicity of grade 3 or higher was observed during reirradiation. Severe (grade 3 or above) late toxicities included xerostomia (n=1), hearing impairment (n=2), temporal lobe injury (n=1) and mucosal necrosis (n=19). Conclusions IMCT is an efficacious and safe treatment for patients with locoregionally recurrent nasopharyngeal carcinoma with acceptable toxicity profile. Long-term follow-up is necessary to further evaluate the long-term efficacy and late toxicities. Key words: Nasopharyngeal neoplasm/intensity-modulated carbon ion radiotherapy; Second-course radiotherapy; Treatment outcome

High-dose-rate intracavitary brachytherapy for non-palpable and non-visible recurrent vaginal stump tumors after hysterectomy

Purpose: The purpose of this study was to evaluate patients who were treated with high-dose-rate (HDR) intracavitary brachytherapy for non-palpable and non-visible recurrent vaginal stump that occurred after hysterectomy. Materials and Methods: This retrospective study included 11 patients aged 52–81 (median, 61) years. The HDR brachytherapy was performed using a remote after-loading system (RALS). The dose per fraction was planned at mainly 4 Gy/fraction, twice per week, for a total of 32 Gy. Results: CR and PR were diagnosed on cytology or visual examination in nine (82%) patients and in one (9%) patient, respectively. SD was noted in one (9%) patient. Isolated stump recurrence developed in five patients and the three-year LC rate was 53%. There was no severe acute and late toxicity. Conclusion: Local salvage is possible with a three-year LC rate of 53% with regard to non-palpable and non-visible limited vaginal recurrence of gynecological cancer that responds to HDR brachytherapy (4 Gy/fraction, total 32 Gy).