Late Toxicity Rates Research Articles

Moderately hypofractionated radiotherapy for localized prostate cancer: updated long-term outcome and toxicity analysis

PurposeEvaluation of long-term outcome and toxicity of moderately hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost treatment planning and cone beam CT-based image guidance for localized prostate cancer.MethodsBetween 2005 and 2015, 346 consecutive patients with localized prostate cancer received primary radiotherapy using cone beam CT-based image-guided intensity-modulated radiotherapy (IG-IMRT) and volumetric modulated arc therapy (IG-VMAT) with a simultaneous integrated boost (SIB). Total doses of 73.9 Gy (n = 44) and 76.2 Gy (n = 302) to the high-dose PTV were delivered in 32 and 33 fractions, respectively. The low-dose PTV received a dose (D95) of 60.06 Gy in single doses of 1.82 Gy. The pelvic lymph nodes were treated in 91 high-risk patients to 45.5 Gy (D95).ResultsMedian follow-up was 61.8 months. The 5‑year biochemical relapse-free survival (bRFS) was 85.4% for all patients and 93.3, 87.4, and 79.4% for low-, intermediate-, and high-risk disease, respectively. The 5‑year prostate cancer-specific survival (PSS) was 94.8% for all patients and 98.7, 98.9, 89.3% for low-, intermediate-, and high-risk disease, respectively. The 5‑year and 10-year overall survival rates were 83.8 and 66.3% and the 5‑year and 10-year freedom from distant metastasis rates were 92.2 and 88.0%, respectively. Cumulative 5‑year late GU toxicity and late GI toxicity grade ≥2 was observed in 26.3 and 12.1% of the patients, respectively. Cumulative 5‑year late grade 3 GU/GI toxicity occurred in 4.0/1.2%.ConclusionModerately hypofractionated radiotherapy using SIB treatment planning and cone beam CT image guidance resulted in high biochemical control and survival with low rates of late toxicity.

Radiothérapie stéréotaxique des tumeurs primitives extracrâniennes

Stereotactic radiotherapy is a fundamental change from the conventional fractionated radiotherapy and represents a new therapeutic indication. Stereotactic radiotherapy is now a standard of care for inoperable patients or patients who refuse surgery. The results are encouraging with local control and survival rates very high in selected populations. The rate of late toxicity remains acceptable. Good tolerability makes it appropriate even for elderly and frail patients. In these fragile patients or in certain specific clinical situations, different surgical, radiotherapy or interventional radiology attitudes can be discussed on a case-by-case basis. These situations are considered in this article for the pulmonary, hepatic and prostatic localizations.

Abstract 6284: GC4419 protects again radiation induced oral mucositis, enhances the response of squamous cell carcinoma of the head and neck tumors to ionizing radiation, and enhances radioimmune therapy

Abstract Locoregional recurrence (LRR) is the major cause of morbidity and mortality in patients with squamous cell carcinoma of the head and neck (HNSCC). For those patients that experience surgically unresectable LRR, median overall survival (OS) is less than one year. Approaches utilizing stereotactic ablative radiotherapy (SAbR) and immune oncology agents such as Nivolumab (α-PD-1 agonist) in the salvage setting have become alternatives to conventional chemoradiation therapy. Despite improvements in OS, rates of acute oral mucositis (OM) and late toxicities (skin fibrosis) remain a concern with SAbR, particularly in the context of re-irradiation. Here we present pre-clinical evidence that GC4419 (Galera Therapeutics), a highly selective superoxide dismutase mimetic that recently received FDA Breakthrough therapy status following a Phase II, randomized, placebo controlled trial for reducing the duration and incidence of severe OM in patients undergoing chemoradiation therapy for locally advanced HNSCC (NCT02508389) also enhances the anti-tumor radiation response of HNSCC tumors to irradiation. We demonstrate in pre-clinical animal models that GC4419 protects the normal mucosa of the mouse tongue from radiation exposure. Utilizing clonogenic survival assays, GC4419 demonstrates single agent anti-cancer activity at physiologically achievable concentrations, while also enhancing the response of HNSCC lines to irradiation. In tumor growth delay (TGD) experiments utilizing the syngeneic HNSCC tumor model, AT-84, when GC4419 is delivered 30-60 minutes pre-irradiation with biologically equivalent fractionation schedules of 17 Gy x 1 fxn, 10.24 Gy x 2 fxn, or 5 Gy x 5 fxn, an enhancement of the radiation response is achieved. In tumor cure rate (TCD50) studies, GC4419 enhanced radiation exposure with a DEF of 1.25. Furthermore, when GC4419 is combined with radiation and an α-PD-1 inhibitor, a further enhancement of the radiation response is observed, indicating that GC4419 compliments radiotherapy combined with immune oncology. We will also report the results of ongoing studies examining the potency of GC4419 in protecting normal murine mucosa in the setting of reirradiation relevant to SAbR as a salvage therapy. This potentiation of the anti-tumor response with GC4419 is more pronounced at doses exceeding the threshold to be considered for intensity modulated radiation therapy (IMRT). The accompanying pre-clinical data strongly suggest that GC4419 should be combined with radio-immune therapy to not only enhance local tumor control, but that the potential for normal tissue protection with SAbR also creates the opportunity for dose escalation and may further improvement in treatment outcome. Citation Format: Brock James Sishc, Elizabeth Polsdofer, Debabrata Saha, Michael Story. GC4419 protects again radiation induced oral mucositis, enhances the response of squamous cell carcinoma of the head and neck tumors to ionizing radiation, and enhances radioimmune therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6284.

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...

Accelerated partial breast irradiation by brachytherapy: present evidence and future developments.

Accelerated partial breast irradiation (APBI) delivers a short course of adjuvant RT after breast conserving surgery to only a limited part of the breast where the tumor was located. This procedure requires expertise, good communication, and close collaboration between specialized surgeons and attending radiation oncologists with adequate intraoperative tumor bed clip marking. However, APBI offers several intrinsic benefits when compared with whole breast irradiation (WBIR) including reduced treatment time (1 versus 4-6weeks) and better sparing of surrounding healthy tissues. The present publication reviews the APBI level 1-evidence provided with various radiation techniques supplemented by long-term experience obtained from large multi-institutional phase II studies. Additionally, it offers an outlook on recent research with ultra-short or single-fraction APBI courses and new brachytherapy sources. Mature data from three randomized controlled trials (RCTs) clearly prove the noninferiority of APBI with 'only two techniques-1/MIBT (multicatheter interstitial brachytherapy) (two trials) and 2/intensity modulated radiotherapy (one trial)'-in terms of equivalent local control/overall survival to the previous standard 'conventionally fractionated WBIR'. However, MIBT-APBI techniques were superior in both toxicity and patient-reported outcomes (PROs) versus WBIR at long-term follow-up. Currently, in RCT-setting, alternative APBI techniques such as intraoperative electrons, 50-kV x-rays and three-dimensional conformal external beam radiotherapy (3D-CRT) failed to demonstrate noninferiority to conventionally fractionated WBIR. However, 3D-CRT-APBI compared noninferior to hypo-fractionated WBIR in preventing ipsilateral breast tumor recurrence (randomized RAPID-trial) but was associated with a higher rate of late radiation toxicity. Ultimately, MIBT remains the only APBI modality with noninferior survival/superior toxicity/PROs at 10-years and therefore should be prioritized over alternative methods in patients with breast cancer considered at low-risk for local recurrence according to recent international guidelines.

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

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

Is the toxicity of breast radiotherapy higher in patients with collagen vascular disease? A systematic review of the literature.

e12527 Background: Collagen vascular disease (CVD) has been described to be a relative contraindication for radiotherapy (RT) due to increased toxicity. As a result, RT to the breast or chest wall is underutilized in patients with CVD, despite known benefits in local control and overall survival after breast conserving surgery or mastectomy. We sought to characterize the acute and late toxicity rates associated with curative-intent RT for breast cancer patients with CVD. Methods: A systematic review per the PRISMA guidelines was performed using Pubmed database (inception to July 2019), for English-language articles. Key search themes included collagen vascular disease, connective tissue disease, including specific subtypes, along with terms for radiation and cancer. Title and abstract review were followed by full-text review. Inclusion criteria were reports of toxicity of five or more patients with CVD and treatment with curative-intent RT to the breast or chest wall. Data abstracted included: type of study, CVD diagnosis, number of patients who received breast RT, acute grade ≥3, and late grade ≥1, grade ≥3, and grade 5 toxicity. Primary endpoint was late grade ≥3 toxicity for patients with pre-existing CVD. Acute and late toxicity were classified as per CTCAE version 5.0. Results: The initial search yielded 3286 unique abstracts. 34 articles were determined appropriate for full-text review. From these, a final set of 10 articles met all inclusion criteria. All studies were retrospective. In these studies, more than 30 000 patient cases were reported. 184 patients with CVD who underwent curative-intent RT to the breast or chest wall and had available toxicity data were identified, including 128 patients with CVD diagnosed before RT. In the 5 case control studies, 100 patients were matched to 225 controls. Most studies did not report the incidence of all grades of toxicity. Among patients with available data, 7/102 patients (7%) with pre-existing CVD had late grade ≥3 toxicity, including 4/6 (67%) with pre-existing scleroderma and 3/96 (3%) with pre-existing non-scleroderma CVD. 32/88 patients (36%) with pre-existing CVD and available data had late grade ≥1 toxicity. 1/142 (1%) had late grade 5 toxicity, in the form of chronic pericarditis. 6/66 patients (11%) with pre-existing CVD had acute grade ≥3 radiation dermatitis. No patients had acute grade 5 toxicity. Conclusions: Retrospective data suggest that patients with pre-existing CVD, aside from scleroderma, have acceptable acute and late toxicity rates after RT to the breast or chest wall.

When It Comes to Snakebites, Kids Are Little Adults: a Comparison of Adults and Children with Rattlesnake Bites

Rattlesnake envenomations are a significant cause of morbidity in the USA. While pediatric rattlesnake envenomations are relatively common, data comparing adult and pediatric patients with rattlesnake envenomationsremain limited. This multi-center retrospective study used the North American Snakebite Registry (NASBR), a sub-registry of the Toxicology Investigator's Consortium (ToxIC). All cases of rattlesnake envenomations between January 1, 2013, and December 31, 2017, which were entered into the NASBR, were reviewed. Clinical and laboratory parameters, as well as treatment and outcome measurements, were compared between adult and pediatric patients. A total of 420 unique cases were identified, including 94 pediatric patients. Adult patients were more likely to be male(76% vs. 62%; OR 1.98) and sustain upper extremity envenomations(57% vs. 25%; OR 4.4). After adjusting for bite location, adults were more likely to exhibit edema compared with pediatric patients. After controlling for envenomation location, there was no difference in rates of necrosis between adult and pediatric patients. Adults exhibited early hematologic toxicity less frequently than pediatric patients, but there was no difference in the rates of late hematologic toxicity. There were no differences in the rates of hypotension or intubation. While adult and pediatric patients have some differences in envenomation characteristics and laboratory parameters, adults and pediatric patients had similar rates of systemic toxicity, severity, length of stay, and late hematologic toxicity.

Urinary Morbidity in Men Treated With Stereotactic Body Radiation Therapy (SBRT) for Localized Prostate Cancer Following Transurethral Resection of the Prostate (TURP).

Background: Clinical data suggest that stereotactic body radiation therapy (SBRT) provides similar clinical outcomes as other radiation modalities for prostate cancer. However, data reporting on the safety of SBRT after TURP is limited. Herein, we report our experience using SBRT to deliver hypofractionated radiotherapy in patients with a history of TURP including physician-reported toxicities and patient-reported quality of life.Methods: Forty-seven patients treated with SBRT from 2007 to 2016 at Georgetown University Hospital for localized prostate carcinoma with a history of prior TURP were included in this retrospective analysis. Treatment was delivered using the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) with doses of 35 Gy or 36.25 Gy in 5 fractions without prostatic urethral sparing. Toxicities were recorded and scored using the CTCAE v.4. Cystoscopy findings were retrospectively reviewed. Urinary quality of life data was assessed using the International Prostate Symptom Scoring (IPSS) and Expanded Prostate Cancer Index Composite 26 (EPIC-26). A Wilcoxon signed-rank sum test was used to determine if there was a statistically significant increase or decrease in IPSS or EPIC scores between timepoints. Minimally important differences were calculated by obtaining half the standard deviation at time of start of treatment.Results: Forty-seven patients at a median age of 72 years (range 63–84) received SBRT. The mean follow-up was 4.7 years (range 2–10 years). Late Grade 2 and grade 3 urinary toxicity occurred in 23 (48.9%) and 3 (6.4%) men, respectively. There were no Grade 4 or 5 toxicities. Approximately 51% of patients experienced hematuria following treatment. Mean time to hematuria was 10.5 months. Twenty-five cystoscopies were performed during follow-up and the most common finding was hyperemia, varices of the bladder neck/TURP defect, and/or necrotic tissue in the TURP defect. Baseline urinary QOL composite scores were low, but they did not clinically significantly decline in the first 2 years following treatment.Conclusions: In patients with prior TURP, prostate SBRT was well-tolerated. GU toxicity rates were comparable to similar patients treated with conventionally fractionated radiation therapy. Urinary quality of life was poor at baseline, but did not worsen clinically over time. Stricter dosimetric criteria could potentially improve the rate of high-grade late toxicity, but may increase the risk of peri-urethral recurrence.

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.

5-Year Update of a Multi-Institution, Prospective Phase 2 Hypofractionated Postmastectomy Radiation Therapy Trial

Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen. Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications. After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%. This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.

Post-mastectomy immediate breast reconstruction and adjuvant radiotherapy: long term results of a mono institutional experience.

The aim of this paper is to investigate the outcome of patients treated with mastectomy, immediate breast reconstruction (IBR) and post-mastectomy radiotherapy (PMRT) and the risk of late complications. All patients had post-mastectomy, immediate reconstructive surgical procedure by using autologous abdominal implant; tissue expander (TE)/permanent prosthesis (PP); or even combined procedures. Adjuvant external beam radiotherapy treatment (EBRT) was delivered to the reconstructed chest wall and supraclavicular nodes, for a total dose of 50Gy in 25 fractions. The Kaplan-Meyer analysis evaluates patients' rate of late side effects, Overall Survival (OS), Progression Free survival (PFS), Local-regional free survival (LRFS) and Metastasis Free Survival (MFS). The univariate analysis investigates the correlation between late toxicity and related factors. Between November 2003 and October 2016, 91 breast cancer patients were treated with IBR and PMRT. Twenty-three (25.3%) patients experimented late toxicity. Overall, 16 (17.6%) patients experienced late complications which required a surgical approach. The 1- 2- 5- years late toxicity rates were 96.6%, 87.1% and 77.9%, respectively. The type of reconstruction was not statistically related with late toxicity rate (P = 0.35). The median follow-up period was 59months (range 6-142months). Median OS was not reached, the 1- 2- 5-years OS rates were 100%, 95.4% and 81% respectively. This study underlines that the type of reconstruction does not influence late toxicity rate. Moreover, IBR followed by adjuvant radiotherapy, has showed acceptable late toxicity profile and no influence on OS.

18F-choline PET/CT driven salvage radiotherapy in prostate cancer patients: up-date analysis with 5-year median follow-up.

Salvage radiotherapy is generally considered as the standard treatment for biochemical relapse after surgery. Best results have been obtained with a PSA value < 0.5ng/ml at relapse, while 60-66Gy is deemed as standard total dose. Modern imaging, as dynamic-18F-choline PET/CT may identify site of recurrence, allowing dose escalation to a biological target volume. Hundred and fifty patients showed a local relapse at dynamic-18F-choline PET/CT at time of biochemical recurrence. High-dose salvage radiotherapy was delivered up to total dose of 80Gy to 18F-choline PET/CT positive area. Toxicity and relapse-free survival were recorded. Median PSA value at the beginning of salvage radiotherapy was 0.47ng/ml (range 0.2-17.5ng/ml). One-hundred and thirty nine patients (93%) completed salvage radiotherapy without interruptions. Acute gastrointestinal grade ≥ 2 toxicity was recorded in 13 patients (9%), acute genitourinary grade ≥ 2 toxicity in 2 patients (1.4%). One patient (0.7%) experienced late gastrointestinal grade 4 toxicity and 2 patients (1.4%) late acute genitourinary grade 3 toxicity. With a median follow-up of 63.5months, 5 and 7-years relapse-free survival were 70% and 60.7%, respectively. With a median follow-up of 5years the present study confirms that high-dose salvage radiotherapy to a biological target volume is feasible, with low rate of late toxicity and promising activity.

5 years of experience with DIBH (Deep inspiration breath-hold) combined with SGRT (Surface-Guided Radiation Therapy) in left-sided breast cancer

Abstract Background Radiation treatment to the left breast is associated with increased cardiac morbidity as well as mortality. Deep inspiration breath-hold (DIBH) technique with Surface Guided Radiation Therapy (SGRT) could have dosimetric advantages over the free breathing technique (NB, normal breathing) in cardiac (heart and LAD) and ipsilateral lung sparing in patients with left-sided breast cancer after surgery. Therefore this technique was implemented in 2013 at the institute of radiooncology at the KFJ/SMZ-South – Hospital Vienna. Methods From Oct 2013 – December 2018 548 patients were referred to radiotherapy following conservative operation of left-sided invasive breast cancer. All patients gave their informed consent and underwent training sessions for the DIBH-technique independent of age or breathing activity or respiratory disorders. Patients who turned out to be unfit for DIBH were enrolled for NB. The relative reduction in Dmean heart and left lung dose was compared between the two cohorts. Acute radiation induced side effects were classified according to the Radiation Therapy Oncology Group/The European Organisation for Research (RTOG) 37; late toxicity rates according to the Common Terminology Criteria for Adverse Events (CTCAE Version 4.03) Results The median age of the DIBH-patients was 58 years (27–90), of the NB-patients 65 (30–80) years. Follow-up was obtained until June 2019. The median follow-up was 52 months (range 7–73 m). The average coverage of Dmean left lung was 6.91 Gy (1.44 Gy – 12.4 Gy). The average coverage of Dmean heart was 1.17 Gy (0.12 Gy – 3.19 Gy) in the DIBH-cohort. The NB – plans had a Dmean of 8.92 Gy (5.23–16.9 Gy) at the ipsilateral lung and a Dmean of 2.31 Gy (0.71–4.21 Gy) at the heart. This shows that the DIBH-technique halved the Dmean of the heart. The amount of acute side effects was comparable between the two groups: RTOG 1: 70.8 % vs. 64 %, RTOG 3 6.6 % vs. 5.6 %, no reaction 3.2 % vs. 1.4 %. There were more CTCAE 1-late events in the NB-group (51.6 % vs. 12.67 %). Conclusion Deep inspiration breath-hold (DIBH) technique with Surface Guided Radiation Therapy (SGRT) is a rather simple, reproducable method with a high acceptance of the patients who can actively participate in the whole treatment process. The mean dose at the heart and the left lung can be reduced, at the heart even by as much as 50 %.

Patterns of use of chemotherapy with radiotherapy in the treatment of muscle-invasive bladder cancer: Data from the RAIDER randomized trial of adaptive radiotherapy.

503 Background: Level 1 evidence exists for the use of both neoadjuvant chemotherapy (NAC) and concomitant radiosensitization (CRS) to improve outcomes in patients receiving radical radiotherapy (RT) for muscle invasive bladder cancer, but uptake has been patchy. We report here the current patterns of usage in an ongoing trial of adaptive radiotherapy. Methods: RAIDER is an international randomized phase II trial recruiting patients with unifocal T2-T4a urothelial carcinoma of the bladder suitable for RT (ISCRTN:26779187). Patients are randomized in a 1:1:2 ratio to one of 3 arms: Standard whole bladder RT (control); Standard dose adaptive tumour focused RT; Dose escalated (DE) adaptive tumour boost RT. Standard dose patients are treated to either 64Gy/32f or 55Gy/20f and DE patients to 70Gy in 32f or 60Gy in 20f. Patients are encouraged to receive NAC and CRS. The primary endpoint is the rate of late toxicity 6-18 months post treatment in arm 3, with secondary endpoints of patient reported and disease related outcomes. Results: To August 2019, 285 patients had been recruited. Median age is 72 years (IQR 67-79). Stage of disease is T2 79%, T3 19%, T4 2%; 19% have hydronephrosis. Patients receiving NAC were more likely to be PS 0 at trial entry (70% v 45%). Variation in frequency of CRS use is seen across sites, with some offering to &gt;90% of participants and some &lt;50%. Data on NAC and CRS use is available for 249 patients recruited to date is shown in table. Conclusions: In this ongoing clinical trial the majority of patients are receiving NAC and/or CRS. However, uptake is not universal with ~30% of patients not receiving low dose CRS, including some who have received NAC. Clinical trial information: 26779187. [Table: see text]

Treatment compliance and early toxicity in SAKK 01/10: Single-dose carboplatin and involved-node radiotherapy for treatment of stage IIA/B seminoma.

405 Background: Standard treatment options for stage IIA/B seminoma include either extensive paraaortal/pelvic radiotherapy or intensive chemotherapy with 3x BEP or 4x EP. Both treatment modalities are associated with excellent efficacy but also a high rate of acute and late toxicities. Therefore, de-escalation strategies appear warranted for this patient group aiming to minimize acute and long-term toxicities while maintaining efficacy. SAKK 01/10 is a joint project of the Swiss Group for Clinical Cancer Research and the German Testicular Cancer Study Group. Methods: Patients with stage IIA/B seminoma (de novo or relapse on active surveillance) were eligible for participation in this single arm phase II trial. A repeat scan was advised in patients with equivocal lymph node enlargement. Treatment consisted of one cycle carboplatin AUC7 followed by involved-node radiotherapy with 30 Gy in stage IIA and 36 Gy in stage IIB disease. The primary endpoint of the trial is 3-year progression free survival. We report on treatment compliance and early toxicity during treatment and within 30 days. Results: 120 patients with stage IIA/B seminoma were recruited from 10/12 until 06/18 in 20 study centers in Switzerland and Germany. 116 patients were eligible and initiated treatment per protocol (40% stage IIA, 60% stage IIB). All patients received chemotherapy (CT) with a median applied dose of 984 mg (range: 560-1920 mg). The median planning target volume (PTV) for radiotherapy (RT) was 297 cm3 (range: 24-1047 cm3). RT was delayed/interrupted in two patients due to adverse events. During CT, grade 2 and grade 3 adverse events were seen in 21% and 2% of all patients respectively (most common grade 2 events: neutropenia 6%, nausea 5%). During RT, grade 2 and grade 3 adverse events were seen in 26% and 6% of all patients respectively (most common grade 2 events: neutropenia 15%, nausea 6%). One case of transient creatinine increase was reported as a severe adverse event, resolving without sequelae. Conclusions: Treatment with one cycle carboplatin AUC7 and 30-36 Gy involved-node radiotherapy for stage IIA/B seminoma is feasible and demonstrates a very favorable early toxicity profile. Clinical trial information: NCT01593241.

Reirradiation of salivary gland tumors with carbon ion radiotherapy at CNAO

AimsTo report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. MethodsFrom November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. ResultsMajority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. ConclusionsCIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

The role of brachytherapy for margin control in oral tongue squamous cell carcinoma

BackgroundThe aim of this study is to assess the feasibility and effectiveness of using peri-operative brachytherapy (BRTx) for positive/narrow margins present post primary surgical resection of oral tongue squamous cell carcinoma (OTSCC).MethodsProspective single-centre study of patients with OTSCC (T1–3, N0–3, M0) treated with resection of primary tumour ± regional nodal resection and intra-operative insertion of BRTx catheters. BRTx was administered twice daily at 40.8Gy/12Fr for ‘Positive’ (≤2 mm) margins, at 34Gy/10Fr for ‘Narrow’ (2.1-5 mm) margins, and not given for ‘Clear’ (> 5 mm) margins over the course of 5–6 days, 3–5 days post operatively.ResultsOut of 55 patients recruited 41 patients (74.6%) were treated with BRTx, as 12 patients had clear margins and 2 patients had unfavourable tumour anatomy for catheter insertion. EBRTx was avoided in 64.3% of patients. Overall Survival (OS) at 3 and 5 years was 75.6 and 59.1% respectively, while Disease Specific Survival (DSS) was 82.3 and 68.6% at 3 and 5 years respectively. Recurrence and survival outcomes were not associated with margin status or the use of or specific dose of BRTx on Cox regression analysis. Acute and late toxicity secondary to BRTx was minimal.ConclusionsThe use of BRTx after primary OTSCC resection with positive/narrow margins ± EBRTx to the neck ± CTx achieves outcomes comparable to traditional treatment of surgery followed by re-resection or EBRTx ± CTx. Morbidity associated with oral cavity EBRTx or secondary resection and reconstruction is thus avoided. Both acute and late toxicity rates are low and compare favourably with other BRTx OTSCC studies.Trial registrationRetrospectively registered. https://www.mcgill.ca/rcr-rcn/files/rcr-rcn/2017.06.05_rcn_hn.pdf.Level of evidence4Graphical abstract

Late results of a randomized trial on the role of mild hypofractionated radiotherapy for the treatment of localized prostate cancer.

Background: Prostate cancer is considered to be highly sensitive to changes in radiation therapy dose per fraction, specifically to hypofractionation. An increase in the fractionation dose could cause a higher increase to the prostate than to the normal tissues leading to better disease control with less toxicity. Here we present the results of a randomized trial comparing mild hypofractionation to conventional fractionation after a median of 3,6 years follow up. Patients and Methods: 139 patients were randomized to receive either hypofractionated radiotherapy with 2,25 Gy/fr to a total of 72 Gy (arm 1) or conventionally fractionated treatment with 2Gy/fr to a total of 74 Gy (arm 2). 72 patients were assigned to arm 1 and 67 to arm 2. Results: After a median follow up of 3,6 years, 23 patients (31,9%) from arm 1 developed grade≥ 2 acute genitourinary toxicity and 21 (31,3%) from arm 2 (p=0,79). The corresponding values from gastrointestinal were 15 (20,8%) and 12 (17,9%) (p=0,6). For late toxicity from GU, 8 patients (11,1%) developed grade≥ 2 symptoms in arm 1 and 7 (10,4%) in arm 2 (p=0,92). late GI toxicity grade≥ 2 was observed in 8 (11,1%) patients in arm 1 and 8 (11,9%) in arm 2 (p=0,88). In multivariate analysis, hormone therapy was significantly associated with late GI events, while acute toxicity from both GU and GI was a prognostic factor of late adverse reaction. Conclusion: No difference in the toxicity profile could be identified between hypofractionation and conventional fractionation. Our schedule of 2,25Gy/fr seems safe and tolerable by the patients with acceptable rates of acute and late toxicity.