Late Toxicity Grade Research Articles

Multi-Institutional Retrospective Analysis of the Outcomes of Proton Beam Therapy for Patients With 1 to 3 Pulmonary Oligometastases From Various Primary Cancers

PurposeOur purpose was to evaluate the efficacy of proton beam therapy (PBT) in patients with 1 to 3 pulmonary oligometastases from various primary cancers in Japan. Methods and MaterialsThis multi-institutional retrospective survey included 118 patients with 141 metastatic lung tumors from miscellaneous primary cancers, across 6 Japanese institutions, and involved the analyses of local progression-free rate (LPF), distant progression-free rate, progression-free survival rate, cause-specific survival rate, and overall survival rate (OS). Treatment-induced adverse effects of grade ≥2 were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0). Cox proportional hazards regression models were used in univariable analysis and multivariable analysis (MVA) for the identification of the prognostic factors of LPF and OS. ResultsThe median follow-up duration from the time of PBT was 25.5 months. The major primary disease sites included colorectal cancer (42.4%), lung cancer (11.9%), head and neck cancer (8.5%), and kidney cancer (8.5%). For years 1, 2, and 3, LPFs were 92.2%, 86.3%, and 78.4%; distant progression-free rates were 59.1%, 44.1%, and 34.0%; progression-free survival rates were 49.6%, 31.7%, and 24.2%; cause-specific survival rates were 83.4%, 72.5%, and 64.8%; and OS rates were 79.0%, 67.8%, and 59.6%, respectively. Eight patients developed acute adverse effects (grade ≥2). Ten patients developed radiation pneumonitis (grade 2) as a late adverse effect. None of the patients developed severe late toxicity (grade ≥3). Colorectal cancer as the primary disease was the only prognostic factor associated with LPF that remained independently significant in the MVAs performed using 3 sets of parameters (hazard ratio [HR], 3.31-4.76 in 3 MVA sets). In the MVA, the significant prognostic factors for OS were performance status (HR, 2.78; 95% confidence interval, 1.01-7.67) and total tumor volume (HR, 1.01; 95% confidence interval, 1.00-1.02). ConclusionsPBT provides promising outcomes for pulmonary oligometastasis with acceptable toxicities.

Multi-institutional registry study evaluating the feasibility and toxicity of accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy

PurposeThe noninvasive image-guided breast brachytherapy (NIBB) technique is a novel noninvasive yet targeted method for accelerated partial breast irradiation. We established a multi-institutional registry to evaluate the toxicity and efficacy of this technique across various practice settings. Methods and MaterialsInstitutions using the NIBB technique were invited to participate. Data for acute/late toxicity, cosmetic outcome, and tumor recurrence were collected. Toxicity and cosmetic outcome were graded based on the Common Terminology Criteria for Adverse Events version 3.0 and NRG/Radiation Therapy Oncology Group scale, respectively. Treatment variables were analyzed for association with outcomes. ResultsA total of 252 patients from eight institutions were analyzed. The median age was 69 years. The mean tumor size was 1.1 cm (0.1–4.0 cm). Treatment was delivered 10 fractions (34–36 Gy) in 75% and five fractions (28.5 Gy) in 22%. B.i.d. fractionation was used in 9%. Acute radiation dermatitis was Grade 0–1, 2, and 3 in 77%, 19%, and 4%, respectively. One hundred ninety-one patients with a median followup of 18 months (4–72 months) were evaluable for late outcomes. Late toxicity Grades 2 and 3 were observed in 8.8% and 1%, respectively. Cosmetic outcome was excellent, good, and fair/poor in 62%, 36%, and 2%, respectively. B.i.d. fractionation was associated with higher acute and late toxicity. Second-generation applicators were associated with lower late toxicity and better cosmetic outcome. Actuarial freedom from ipsilateral breast tumor recurrence and true recurrence were 98.3% and 98.3% at 2 years and 90.9% and 95.4% at 5 years, respectively. ConclusionsAccelerated partial breast irradiation using NIBB was well tolerated with a low rate of acute and late toxicity across various practice settings. Ipsilateral breast tumor recurrence and cosmetic outcomes were favorable. b.i.d. fractionation was associated with higher toxicity. Longer followup is needed to confirm late endpoints.

Comparison of efficacy and safety of three induction chemotherapy regimens with gemcitabine plus cisplatin (GP), cisplatin plus fluorouracil (PF) and cisplatin plus capecitabine (PX) for locoregionally advanced previously untreated nasopharyngeal carcinoma: A pooled analysis of two prospective studies.

We compared, in this pooled analysis, the differences in efficacy and safety between three induction chemotherapy regimens including gemcitabine plus cisplatin (GP), cisplatin plus fluorouracil (PF) and cisplatin plus capecitabine (PX) in patients recruited into our two prospective studies for previously untreated locoregionally advanced nasopharyngeal carcinoma (NPC). GP, PF or PX followed by radical concurrent chemoradiotherapy was given to patients with previously untreated locoregionally advanced (stage III to IVA) NPC prospectively recruited into our two prospective studies. The study endpoints included progression-free survival (PFS) and overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and major acute and late treatment-related toxicities (grade≥3). From 2006 to 2016, 278 patients were enrolled (84, 94 and 100 patients in GP, PF and PX group respectively). After a median follow-up of 80months, the 3-year PFS, OS, LRFS, DMFS and CSS of the whole population were 78.7%, 88.1%, 84.9%, 80.9% and 89.8%, respectively. There were no significant differences in prespecified survival endpoints among GP, PF and PX in both stage III and stage IVA patients. GP had lower incidences of severe (grade≥3) anemia and diarrhea in stage III patients, as well as severe anemia, dehydration, renal impairment and vomiting in stage IVA patients. The incidences of grade≥3 late toxicities were similar among these 3 induction regimens. GP had similar efficacy and potentially fewer treatment-related complications compared with PF and PX as induction chemotherapy for previously untreated locoregionally advanced NPC.

Predicting Radiotherapy Impact on Late Bladder Toxicity in Prostate Cancer Patients: An Observational Study.

Simple SummaryProstate cancer (PC) is the most common cancer in men over 70 years old, with heterogeneous characteristics and, nowadays, multiple treatment strategies obtaining optimal outcomes and improving survival. Personalized medicine and even more morbidity treatment reduction are increasing needs. The development of decision support systems to personalize treatments is a key challenge in oncology. The study PRODIGE 1.1 aimed to elaborate on a model analyzing dosimetric parameters in Prostate Cancer patients treating by radiation therapy, predicting late bladder toxicity in order to customize treatments and reduce late morbidity.Background and purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique. Materials and methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann–Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer–Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3.1 and an in house developed software package “Moddicom” were used. Results: Data from 175 patients were collected. The median follow-up was 39 months (min–max 3.00–113.00). We performed Mann–Whitney rank-sum test with continuity correction in the subset of patients with late bladder toxicity grade ≥ 2: a statistically significant p-value with a Vdose of 51.43 Gy by applying a logistic regression model (coefficient 4.3, p value 0.025) for the prediction of the development of late G ≥ 2 GU toxicity was observed. The performance for the model’s internal validation was evaluated, with an AUC equal to 0.626. Accuracy was estimated through the elaboration of a calibration plot. Conclusions: Our preliminary results could help to optimize treatment planning procedures and customize treatments.

Long-Term Results of Dose-Intensified Fractionated Stereotactic Body Radiation Therapy (SBRT) for Painful Spinal Metastases

To report long-term outcome of fractionated stereotactic body radiation therapy (SBRT) for painful spinal metastases. This prospective, single-arm, multicenter phase 2 clinical trial enrolled 57 patients with 63 painful, unirradiated spinal metastases between March 2012 and July 2015. Patients were treated with 48.5 Gy in 10 SBRT fractions (long life expectancy [Mizumoto score ≤4]) or 35 Gy in 5 SBRT fractions (intermediate life expectancy [Mizumoto score 5-9]). Pain response was defined as pain improvement of a minimum of 2 points on a visual analog scale, and net pain relief was defined as the sum of time with pain response (complete and partial) divided by the overall follow-up time. All 57 patients received treatment per protocol; 32 and 25 patients were treated with 10- and 5-fraction SBRT, respectively. The median follow-up of living patients was 60 months (range, 33-74 months). Of evaluable patients, 82% had complete or partial pain response (responders) at 3 months' follow-up (primary endpoint), and pain response remained stable over 5 years. Net pain relief was 74% (95% CI, 65%-80%). Overall survival rates of 1, 3, and 5 years were 59.6% (95% CI, 47%-72%), 33.3% (95% CI, 21%-46%), and 21% (95% CI, 10%-32%), respectively. Freedom from local spinal-metastasis progression was 82% at the last imaging follow-up. Late grade-3 toxicity was limited to pain in 2 patients (nonresponders). There were no cases of myelopathy. SBRT resulted in long-term improvements of all dimensions of the 5-level EuroQol 5-Dimension Questionnaire except anxiety/depression. Fractionated SBRT achieved durable pain response and improved quality of life at minimum late toxicity.

Evaluation of adjuvant vaginal vault brachytherapy in early stage cervical cancer patients

PurposeAdjuvant external beam radiotherapy (EBRT) was shown to decrease pelvic relapses in patients with an early stage cervical cancer and intermediate-risk histopathological prognostic factors, at the cost of increased bowel morbidity. We examined the feasibility and results of adjuvant brachytherapy alone as an alternative to EBRT in this situation. Patients and methodsMedical records of consecutive patients receiving adjuvant brachytherapy between 1991 and 2018 for an early stage cervical cancer were examined. Patients were included if they presented a pT1a2N0 or pT1b1N0 disease following radical colpohysterectomy. Adjuvant vaginal wall brachytherapy (without EBRT) was indicated because of a tumor size≥2cm and/or presence of lymphovascular space invasion (LVSI). Patients received 60Gy to 5mm of the vaginal wall, through low-dose or pulse-dose rate technique. Patients’ outcome was examined for disease control, toxicities and prognostic factors. ResultsA total of 40 patients were included. Eight patients (20%) had LVSI, 26 patients (65%) had a tumor size≥2cm. With median follow-up time of 42.0 months, 90% of patients were in complete remission and four patients (10%) experienced tumor relapse, all in the peritoneal cavity, and associated with synchronous pelvic lymph node failure in 2/4 patients. No vaginal or isolated pelvic nodal failure was reported. At 5 year, overall survival was 83.6% (CI95%: 67.8–100%) and disease-free survival was 85.1% (CI95%: 72.6–99.9%). In univariate analysis, probability of relapse correlated with tumor size≥3cm (P=0.004). No acute or late toxicity grade more than 2 was reported. ConclusionBrachytherapy alone was a well-tolerated adjuvant treatment for selected patients with intermediate risk factors. The risk of relapse in patients with tumor size≥3cm was however high, suggesting that EBRT is more appropriate in this situation.

Radiotherapy for elder patients aged ≥80 with clinically localized prostate cancer – Brachytherapy enhanced late GU toxicity especially in elderly

Background and purposeElongation of life expectancy had led to marked increase in number of elderly patients with localized prostate cancer. However, the standard treatment for such patients is not well determined because of a high prevalence of comorbidities and slow growth of prostate cancer. The aim of this study is to examine the feasibility of radiotherapy for elderly patients aged ≥80 years. Materials and methodsWe compared 96 patients aged ≥80 years and 2333 younger patients (aged 60–79 years) using multi-institutional data included cT1-T4N0M0 prostate cancer treated with 902 external beam radiotherapy (EBRT) and 1527 brachytherapy (BT). ResultsThe 5-year biochemical failure-free survival rate was similar between elderly ≥80 years and younger control (91.3% vs. 85.9%, p = 0.6171) (100%, 92.9%, 82.4% and 96.3%, 93.7%, 89% for low, intermediate and high risk group), and for the prostate cancer-specific survival rate (100% and 99.3%, p = 0.6171). The accumulated incidence of late gastrointestinal (GI) at 5 years was also similar between elderly and younger patients (3.5% vs. 2.5%, p = 0.6857). Brachytherapy improved biochemical control rate and reduced GI toxicity compared with EBRT, however, enhanced late genitourinary (GU) toxicity, especially in elderly patients. Elderly received brachytherapy showed highest rate of late GU toxicity grade ≥2 of 22.1% than the younger counterparts of 12.7% at 5 years, whereas younger patients treated with EBRT had 2.4% and elderly EBRT had 2.7% (p < 0.0001). ConclusionElderly patients aged ≥80 years showed equivalent biochemical control, prostate cancer-related survival, and gastrointestinal toxicity profiles to younger patients. Meticulous care should be required for brachytherapy enhanced late GU toxicity, especially in elderly patients aged ≥80 years.

Phase II Study: The Outcome of Hypofractionated Involved-Field Radiation Therapy With Concurrent Chemotherapy for the Treatment of Locally Advanced Non-small Cell Lung Cancer

PurposeThis phase II study aimed to evaluate the efficacy and safety of hypofractionated involved-field radiation therapy (HypoFx-IFRT) in 2.5 Gy fractions and concurrent chemotherapy for locally advanced stage IIIA and B nonsmall cell lung cancer (LA-NSCLC) without prolonging treatment delivery time beyond 6 weeks. We analyzed the overall survival (OS), progression-free survival, and safety of the treatment. Methods and MaterialsThis prospective, single center, single-arm trial was initiated in 2010. All LA-NSCLC patients were treated with HypoFx-IFRT using 3-dimensional conformal radiation therapy. The median total dose of HypoFx-IFRT was 67.5 Gy (range, 60-70). ResultsFrom December 2010 to October 2016, 36 patients were ultimately enrolled and evaluated. The trial closed early owing to slow accrual. The median follow-up duration was 50 months in all patients and 65 months in surviving patients. The 1-, 3-, and 5-year OS rates were 88.9% (95% confidence interval [CI], 78.6%-99.2%), 61.1% (95% CI, 45.2%-77.0%), and 54.1% (95% CI, 37.3%-70.9%), respectively. The median time for OS was not reached. The median time for progression-free survival was 10.7 months. The incidence rates of grade 3 radiation pneumonitis, esophagitis and esophageal stenosis were 8.3%, 2.8%, and 2.8%, respectively, and no acute or late toxicities of grade 4 or 5 were observed. ConclusionsThis study indicated that HypoFx-IFRT with concurrent chemotherapy yielded an acceptable safety profile and might be beneficial in the survival outcomes of patients with LA-NSCLC.

Proton Accelerated Partial Breast Irradiation: Clinical Outcomes at a Planned Interim Analysis of a Prospective Phase 2 Trial

To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

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.

Evaluation of Uterine Brachytherapy as Primary Treatment Option for Elderly Patients with Medically Inoperable Endometrial Cancer-A Single-Center Experience and Review of the Literature.

We aimed to gain more evidence regarding the feasibility, toxicity, and oncological outcome of primary brachytherapy in patients with medically inoperable endometrial cancer. Thirteen patients receiving primary brachytherapy ± external beam radiotherapy (EBRT) for endometrial cancer due to medical inoperability were identified. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS). Univariate outcome analyses were performed using the log-rank test. Peri-interventional complications, acute and chronic toxicities were evaluated. Additionally, we performed a Pubmed search and review of the literature of the last 10 years. Mean age at time of diagnosis was 73.9 years (60.4–87.1 years). Eleven patients were staged FIGO IA/B and one patient each with FIGO IIIA and IIIC. Kaplan–Meier-estimated 2-/5-year LFFS were 76.2%/56.4%, respectively. High grading correlated with a worse LFFS (p = 0.069). Kaplan–Meier-estimated 2-/5-year PFS were 76.9%/53.8% and 2-/5-year-OS were 76.9%/69.2%, respectively. No acute toxicities > grade II and only two late toxicities grade II/III occurred. We observed three peri-interventional complications. The available evidence suggests high rates of local control after definitive brachytherapy for inoperable endometrial cancer with a favorable toxicity profile. Definitive brachytherapy +/− EBRT should be considered as the preferred approach for this patient group.

Patterns of treatment failure in patients with prostate cancer treated with 76-80Gy radiotherapy to the prostate and seminal vesicles ± hormonotherapy.

To assess the pattern of treatment failure in patients with prostate cancer (PCa) treated with radiotherapy (76-80Gy) ± hormone therapy (HT). We also evaluated the influence of treatment failure on survival outcomes. Retrospective study of patients with PCa (n = 302) treated with radiotherapy (RT) ± HT at our centre between November 1999 and July 2007. The mean patient age was 70.2years (range 51-87). Distribution by NCCN risk group was low (n = 80, 26.5%), intermediate (n = 86, 28.5%), high (n = 77, 25.5%), and very high (n = 49, 16.2%). Most patients (n = 273, 90.4%) received IMRT at a dose of 76-80Gy. HT was administered in 237 patients (78.5%), in most cases (n = 167, 55.3%) for < 7months RESULTS: Survival rates at 10years were: overall survival (OS), 64.3%; biochemical disease-free survival, 83.9%; disease-free survival, 92.5%; and metastasis-free survival (MFS), 94.3%. Biochemical failure (BF) was observed in 55 cases (18.2%), 32 of whom subsequently developed clinical recurrence: metastasis (n = 17, 5.6%), local failure (n = 11, 3.6%), and regional failure (n = 4, 1.3%). The cause of death (n = 159) was intercurrent disease in 115 cases (72.3%), second cancer in 27 (17.0%), and PCa in 17 (10.7%). Biochemical failure-free survival ≤ 24months was significantly associated with worse OS and MFS (p = 0.0001). Late genitourinary and gastrointestinal toxicity grade ≥ 3 (RTOG) was observed in 18 (6.0%) and 7 (2.3%) patients, respectively. The main type of treatment failure after 76-80Gy of radiotherapy ± HT is local or metastatic. In all cases, biochemical failure occurred prior to treatment failure. BF within 24months of treatment completion was significantly associated with worse OS and MFS.

Stereotactic body radiotherapy and systemic dose chemotherapy for locally advanced lung cancer, single-arm phase II study.

e21081 Background: The outcomes for locally advanced non-small cell lung cancer (NSCLC) are overall poor. This is a single arm phase 2 study (Clinical trials.gov NCT02568033) evaluating the role of stereotactic body radiosurgery (SBRT) along with full dose systemic chemotherapy in the treatment of unresectable stage 2 and stage 3 NSCLC. Methods: patients were treated with SBRT to all sites of gross disease. Dosing consisted of 60 Gy in 3 fractions for peripheral lung tumors, 50 Gy in 5 fractions for central lung tumors, and 40-50 Gy in 5 fractions for hilar and mediastinal lymph nodes. Chemotherapy was histology dependent and consisted of 4 cycles, there was a 7 days break between chemotherapy and SBRT. Quality of life was measured using FACT-L. Results: Twenty two patients were enrolled and analyzed. 17 (77 %) were stage III and 19 (86%) had lymph node involvement. Median follow-up for all patients was 23.1 months. Median overall survival is 27.2 months. Overall survival at one year was 82% and overall survival at two years was 53%. Two year regional failure rate 19%. Two year distant failure rate 47.2%. Quality of life scores at one year were available for 12 patients and were unchanged compared to baseline. Acute toxicity grade 3 or greater was seen in 6 patients and late toxicity grade 3 or higher was seen in 2 patients. Conclusions: A combination of SBRT and full dose chemotherapy appears to be a safe and effective treatment for locally advanced NSCLC and warrants further investigation. Clinical trial information: NCT02568033 .

Carbon ion radiotherapy for skull base chordomas and chondrosarcomas: a systematic review and meta-analysis of local control, survival, and toxicity outcomes.

Carbon ion radiotherapy (CIRT) is an emerging radiation therapy to treat skull base chordomas and chondrosarcomas. To date, its use is limited to a few centers around the world, and there has been no attempt to systematically evaluate survival and toxicity outcomes reported in the literature. Correspondingly, the aim of this study was to qualitatively and quantitatively assess these outcomes. A systematic search of seven electronic databases from inception to November 2019 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were then pooled by random-effects meta-analyses of proportions. A total of nine studies provided unique metadata for assessment, with six originating from Heidelberg, Germany. The surveyed cohort size was 632 patients, with 389 (62%) chordomas and 243 (38%) chondrosarcomas of the skull base. Across all studies, median cohort age at therapy and female proportion were 46years and 51% respectively. Estimates of local control incidence at 1-, 5-, and 10-years in chordoma-only studies were 99%, 80%, and 56%, and in chondrosarcoma-only studies were 99%, 89%, and 88%. Estimates of overall survival probability at 1-, 5-, and 10-years in chordoma-only studies were 100%, 94%, and 78%, and in chondrosarcoma-only studies were 99%, 95%, and 79%. The incidence of early and late toxicity (Grade ≥ 3) ranged from 0 to 4% across all study groups. The emerging use of CIRT to treat skull base chordomas and chondrosarcomas appear promising with regard to tumor control, overall survival, and risk profile of early and late toxicity. The current literature suffers from the fact only a few centers in the world currently employ this technology.

The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.

Despite the progresses performed in the field of radiotherapy, toxicity to the healthy tissues remains a major limiting factor. The aim of this work was to highlight blood biomarkers whose variations could predict the occurrence of late cutaneous side effects. Two groups of nine patients treated for Merkel Cell Carcinoma (MCC) were established according to the grade of late skin toxicity after adjuvant irradiation for MCC: grade 0, 1 or 2 and grade 3 or 4 of RTOG (Radiation Therapy Oncology Group)/EORTC (European Organization for Research and Treatment of Cancer). To try to discriminate these 2 groups, biomarkers of interest were measured on the different blood compartments after ex vivo irradiation. In lymphocytes, cell cycle, apoptosis and genotoxicity were studied. Oxidative stress was evaluated by the determination of the erythrocyte antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, reduced and oxidized glutathione) as well as degradation products (protein carbonylation, lipid peroxidation). Inflammation was assessed in the plasma by the measurement of 14 cytokines. The most radiosensitive patients presented a decrease in apoptosis, micronucleus frequency, antioxidant enzyme activities, glutathione and carbonyls; and an increase in TNF-α (Tumor Necrosis Factor α), IL-8 (Interleukin 8) and TGF-β1 (Transforming Growth Factor β1) levels. These findings have to be confirmed on a higher number of patients and before radiotherapy and could allow to predict the occurrence of late skin side effects after radiotherapy.

Toxicity and cosmetic outcome after hypofractionated whole breast irradiation and boost-IOERT in early stage breast cancer (HIOB): First results of a prospective multicenter trial (NCT01343459)

Background and purposeTo assess the role of intraoperative radiation with electrons (IOERT) as tumor bed boost followed by hypofractionated whole breast irradiation (HWBI) after breast conserving surgery (BCS) of patients with low to intermediate risk breast cancer focusing on acute/late toxicity and cosmetic outcome. Material and methodsIn 2011, a prospective multicenter trial (NCT01343459) was started. Treatment consisted of BCS, IOERT (11.1 Gy) and HWBI (40.5 Gy in 15 fractions). In a single-arm design, 5-year IBR-rates are benchmarked by a sequential ratio test (SQRT) against best published evidences in 3 age groups (35–40 y, 41–50 y, >50 y). Acute/late toxicity and cosmesis were evaluated by validated scorings systems. ResultsOf 627 eligible patients, 44 were excluded, leaving 583 to analyze. After a median follow-up (FUP) of 45 months (range 0–74), for acute effects CTCAE-score 0/1 was noted in 91% (end of HWBI) and 92% (4 weeks later), respectively. Late toxicity Grading 0/1 (mean values, ranges) by LENT-SOMA criteria were observed in 92.7% (89–97.3) at 4/5 months, rising to 96.5% (91–100) at 6 years post HWBI. Baseline cosmesis after wound healing prior to HWBI was scored as excellent/good in 86% of cases by subjective (patient) and in 74% by objective (doctor) assessment with no impairment thereafter. ConclusionsAcute and late treatment tolerance of a combined Boost-IOERT/HWBI regimen is excellent in short/mid-term assessment. Postoperative cosmetic appearance is not impaired after 3 years FUP.

Stereotactic body radiotherapy for moderately central and ultra-central oligometastatic disease: Initial outcomes.

Delivery of SBRT to central thoracic tumours within 2 cm of the proximal bronchial tree (PBT), and especially ultra-central tumours which directly abut the PBT, has been controversial due to concerns about high risk of toxicity and treatment-related death when delivering high doses close to critical mediastinal structures. We present dosimetric and clinical outcomes from a group of oligometastatic patients treated with a risk-adapted SBRT approach. Between September 2015 and October 2018, 27 patients with 28 central thoracic oligometastases (6 moderately central, 22 ultra-central) were treated with 60 Gy in 8 fractions under online CBCT guidance. PTV dose was compromised where necessary to meet mandatory OAR constraints. Patients were followed up for toxicity and disease status. Mandatory OAR constraints were met in all cases; this required PTV coverage compromise in 23 cases, with V100% reduced to <70% in 11 cases. No acute or late toxicities of Grade ≥ 3 were reported. One and 2 year in-field control rates were 95.2% and 85.7% respectively, progression-free survival rates were 42.8% and 23.4% respectively, and overall survival rates were 82.7% and 69.5% respectively. No significant differences were seen in control or survival rates by extent of PTV underdosage or between moderately and ultra-central cases. It appears that compromising PTV coverage to meet OAR constraints allows safe and effective delivery of SBRT to moderately and ultra-central tumours, with low toxicity rates and high in-field control rates. This treatment can be delivered on standard linear accelerators with widely available imaging technology.

Determining Optimal Follow-up for Patients With Anal Cancer Following Chemoradiation.

US health care is increasingly defined by over expenditure and inefficiency. Optimizing patient follow-up is critical, especially in cancers treated with high control rates. To optimize patient care, this study assessed time to disease recurrence or toxicity in patients with anal carcinoma. In total, 140 patients with biopsy-proven, nonmetastatic anal carcinoma, treated with chemoradiation utilizing intensity-modulated radiation therapy, were identified from our institutional database. This retrospective study evaluated local recurrence (LR), distant metastasis (DM), overall survival (OS), and late ≥grade 3 toxicity (LG3T). Patients were followed posttreatment every 3 months for 2 years, every 6 months in years 3 to 5, then yearly thereafter per NCCN recommendations. The median age and follow-up was 58 years and 27 months, respectively. Patients were categorized into high (n=61; 44%) and low (n=77; 55%) risk groups based on stage. The 2-year LC, DMFS, and OS were 93%, 94%, and 89% and 5-year LC, DMFS, OS were 92%, 87%, and 85%, respectively. Overall, there were 29 events (9 LR, 11 DM, and 9 LG3T), with 62% of events occurring within year 1 and 79% within 2 years. Stratified by event type, at 2 years 89% of LR, 64% of DM, and 89% LG3T were identified. At the remaining follow-up points, the event incidence rate was 1.3%. With the majority of recurrences/toxicities occurring within the first 2 years, a reduction in follow-up during years 3 to 5 may provide adequate surveillance. Revisions of the current recommendations could maximize resources while improving patient quality of life.

Fecal microbiota transplantation: A promising treatment for radiation enteritis?

BackgroundIncreasing evidence has indicated that gut microbiota is closely associated with radiation-induced bowel injury. We aimed to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in patients with chronic radiation enteritis (CRE). MethodsA pilot study of FMT for CRE was performed. The primary outcomes were safety and response to FMT which was defined as a ≥1-grade reduction in Radiation Therapy Oncology Group (RTOG/EORTC) late toxicity grade from baseline, by 8 weeks post-FMT. The secondary outcomes included a decrease in the severity of four common symptoms (diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence) in CRE and changes in Karnofsky Performance Status (KPS) score. Microbial analyses were performed by 16S rRNA sequencing. ResultsFive female patients underwent FMT from January to November 2018 with a median age of 58 (range 45–81) years. The median baseline RTOG/EORTC grade was 2 (range 2–4). Three patients responded to FMT and experienced improvement in diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence as well as a decrease in KPS score. No FMT-related death and infectious complications occurred. One mild FMT-related AE was observed during a follow-up ranged from 8 to 18 months. 16S rRNA sequencing indicated that FMT altered the composition of gut microbiota of patients. ConclusionThe present case series first demonstrated that FMT might be safe and effective to improve intestinal symptoms and mucosal injury in patients with CRE for a period of time.Trial registration ID: NCT03516461.

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.