Radiation Therapy Oncology Group/European Organization For Research And Treatment Of Cancer Research Articles

Long-Term Anorectal Function in Rectal Cancer Patients Managed by a Watch-and-Wait Strategy after Neoadjuvant Therapy: A Cross-Sectional Study

Rectal cancer patients reaching complete clinical response (cCR) after neoadjuvant chemoradiotherapy can be offered a nonoperative watch-and-wait (W&W) strategy. As evidence of good oncological outcomes accumulates, the functional outcomes remain less explored. The aim of this study is to comprehensively assess the long-term rectal toxicity and anorectal function in patients managed by a W&W strategy and to investigate the clinical risk factors for anorectal dysfunction. Seventy W&W patients who were disease-free at the moment of recruitment were included. A minimum 2-year follow-up was considered. We graded late rectal toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and the Late Effects of Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system. Long-term anorectal function was assessed with the Wexner score, the Low Anterior Resection Syndrome score (LARS score), and the Memorial Sloan Kettering Bowel Function Instrument (MSK BFI). All patients received standard chemoradiotherapy consisting of a total dose of 5000 cGy in 25 fractions. The median tumor distance from the anal verge was 3 (IQR 2-4) cm. After a median follow-up of 43 (IQR 28-66) months, less than half of patients developed Grade 1 (40.0%) or Grade 2 (1.4%) late rectal toxicity, and no patients complained of higher grades. LENT/SOMA criteria also identified more patients with mild symptoms. The most frequent symptoms were sphincter control problems, mainly manifested as fecal urgency, reported by 60.0% of patients. For long-term anorectal function, the median LARS score was 16 (IQR 4-25). 17.1% of patients reported minor LARS and 15.7% reported major LARS. The median Wexner score was 2 (IQR 0-3). The median MSK BFI total score was 82 (IQR 77-86). Smoking history was an independent risk factor for anorectal dysfunction in multivariate analyses (OR = 6.491, 95% CI 1.536-27.432). Rectal cancer patients managed by a watch-and-wait strategy after neoadjuvant chemoradiotherapy have retained satisfactory anorectal function. However, fecal urgency might be a common problem. Smoking history was an independent risk factor for long-term anorectal dysfunction. Prospective studies with emphasis on bowel function outcomes containing a larger number of patients are needed.

High-dose-rate brachytherapy as monotherapy for prostate cancer: 5-year results

Objective: to evaluate clinical outcomes in patients with prostate cancer treated with high-dose-rate (HDR) brachytherapy (BT) as monotherapy.Materials and methods. From January 2015 to December 2017, 97 men with localized prostate cancer underwent HDR-BT as monotherapy, with a temporary implant on a MicroSelectron HDR device. The dose prescription was: 30 Gy in 2 fractions with an interval of 2 weeks. The overall and biochemical survival rate was assessed. The assessment of genitourinary and gastrointestinal toxicity was also carried out. The quality of life associated with urination before treatment and in dynamics during 5 years of observation, as well as the frequency and degree of development of erectile dysfunctionand its dynamics during the entire observation period were analyzed.Results. The median age was 65.2 (44 to 80) years. Overall, 29 patients had low risk prostate cancer, 63 patients had moderate risk, and 5 patients – high risk. The follow-up period was five years (range, 18 to 72 months). The median follow-up was 54.3 (95 % confidence interval 52.3–59) months. Overall survival and survival without biochemical recurrence were 96 and 99 %, respectively. Toxicity was assessed according to the RTOG/EORTC (Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer) scale for each event. Late genitourinary toxic reactions of grade 1 and 2 were noted in 23.9 and 6.3 %, respectively. Late gastrointestinal grade 2 toxicity was not observed. Genitourinary and gastrointestinal toxic reactions of grade 3 were not observed. The quality of life associated with urination after treatment was comparable to the level of quality of life at the time of inclusion of patients in the treatment protocol. Erectile dysfunction developed to a greater extentin the first 1–2 years after HDR-BT with a subsequenttendency to recovery.Conclusion. HDR-BT as monotherapy is a safe and highly effective treatment for localized prostate cancer. The fractionation mode in the form of 30 Gy for 2 fractions of 15 Gy with an interval of 2 weeks with or without dose modulation in the area of the tumor focus using a gel has a low toxicity profile from the side of critical organs.

Induction Chemotherapy Plus Simultaneous Modulated Accelerated Radiation Therapy in Non-operative Hypopharyngeal and Supraglottic Laryngeal Squamous Cell Carcinoma: Long-Term Outcome of a Prospective Phase 2 Study.

Background: To evaluate the toxicities and long-term outcomes of induction chemotherapy (ICT) plus simultaneous modulated accelerated radiation therapy (SMART) in non-operative hypopharyngeal and supraglottic laryngeal squamous cell carcinoma (SCCH/L).Materials and Methods: This was a prospective phase 2 study. Patients diagnosed with SCCH/L, aged from 18 to 75, staged from III to IVB in accordance with the AJCC 2010 criteria, and refusing surgery were eligible. The patients were treated with 2–3 cycles of docetaxel-cisplatin-based ICT and SMART combined with 2–3 cycles of cisplatin-based concurrent chemotherapy. The prescription dose to the primary tumor and metastatic nodes was 69 Gy in 30 fractions. Acute and late toxicities were assessed according to the established Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and long-term outcomes were analyzed.Results: Between February 2013 and June 2015, 55 newly diagnosed SCCH/L patients were enrolled. No grade 2 or worse acute xerostomia was noted. The incidences of grade 3 acute dermatitis, oral mucositis, and pharyngoesophagitis were 12.7, 3.6, and 12.7%, respectively. The median follow-up time was 48 months (range 5.5–74 months). The main late toxicity was hoarseness or sore throat, with an incidence of 32.7%. The 5-year functional larynx-preservation survival was 51.5%. The 3- and 5-year locoregional control and overall survival were 58.2, 51.5, 63.6, and 54.1%, respectively.Conclusions: The ICT plus SMART with a regimen of 69 Gy/30 F for the treatment of SCCH/L demonstrated acceptable severe toxicity, satisfactory long-term outcomes, and laryngeal function preservation.

Frameless Single Robotic Radiosurgery for Pulmonary Metastases in Colorectal Cancer Patients.

BackgroundSurgical intervention and radiation therapy are common approaches for pulmonary metastasectomy. The role of minimally invasive techniques in pulmonary metastases remains unclear. Frameless single robotic radiosurgery [CyberKnife (CK); Accuray Incorporated, Sunnyvale, CA] of pulmonary metastases in colorectal cancer (CRC) patients offers high precision local radiation therapy.MethodsWe analyzed the efficacy and safety of CK treatment for lung metastases in CRC in 34 patients and a total of 45 lesions. The primary endpoint was local control (LC); secondary endpoints were progression-free survival (PFS), overall survival (OS), distant control (DC), and safety-relevant events.ResultsOf the treated lesions, 34/45 (77.8%) decreased in size or remained unchanged [complete response (CR), partial response (PR), stable disease (SD)]; 8/45 (17.8%) lesions increased in size [progressive disease (PD)] and 2/45 (4.4%) lesions were not evaluable. Local progression was shown in 2 lesions (4.4 %). The median PFS period was six months. In a median follow-up time of 19.4 months, medium OS was 19.9 months (range: 3-61 months). Distant recurrence was observed in 21/34 patients (61.8 %). Intrapulmonary progression occurred in six patients. In 4/45 cases, fiducial placement led to a pneumothorax; three out of four patients needed chest tube insertion. No radiation-associated side effects were reported in 57.8% of patients. In 10/45 cases (22.2%), patients suffered asymptomatic radiographic changes; 7/45 cases (15.6%) reported a late onset of radiation-associated side effects. Maximal radiation-associated side effects reached the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Grade 1.ConclusionCK treatment of pulmonary metastases is safe and well-tolerated. For metastatic colorectal cancer (mCRC) patients with pulmonary metastases and not eligible for surgery, CK radiation offers a valuable treatment option.

Expression of vascular endothelial growth factor and its correlation with clinical symptoms and endoscopic findings in patients with chronic radiation proctitis.

The aim of this study was to assess the expression of vascular endothelial growth factor (VEGF) as a key proangiogenic factor and determine whether there is any correlation between its expression and clinical symptoms or endoscopic changes in patients with chronic radiation proctitis (ChRP). Fifty patients who had all undergone radiotherapy for prostate, cervical or uterine cancer were included in the study (37 women, 13 men). There was a control group of 20 patients (9 women, 11 men). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring system was used for grading the severity of the proctitis. Endoscopic scoring of late rectal mucosal damage was performed using Gilinsky's classification. Serum levels of VEGF were analysed by the enzyme-linked immunosorbent assay method. Most patients presented with Grade 1 symptoms. Endoscopic assessment showed that most patients had Grade 1 late rectal mucosal damage. The predominant endoscopic finding was the presence of telangiectasia. Assessment of VEGF correlation between the control group and the degrees of endoscopic changes showed statistically significant differences for all three degrees (P<0.0001, P=0.0251 and P=0.0005, respectively). Due to the small numbers of patients with Grades 2 and 3 symptoms using the RTOG/EORTC scoring system, they were grouped with Grades 1 and 4 respectively forming two groups for statistical purposes. VEGF expression differed significantly between controls and group I and between controls and group II (P=0.0001, P=0.0009, respectively). A significant increase in VEGF expression was found to correlate with clinical symptoms and endoscopic rectal mucosa changes in patients with ChRP, suggesting that it may play an important role in pathological angiogenesis.

Cytoreductive prostate radiotherapy in oligometastatic prostate cancer: a single centre analysis of toxicity and clinical outcome.

ObjectivesThe current standard of care for patients with metastatic prostate cancer (mPCa) at diagnosis is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to define the role of a local radiotherapy (RT) treatment in the mPCa setting.MethodsWe retrospectively reviewed data of patients with PCa and bone oligometastases at diagnosis treated in our institution with ADT followed by cytoreductive prostate-RT with or without RT on metastases. Biochemical and clinical failure (BF, CF), overall survival (OS) and RT-toxicity were assessed.ResultsWe identified 22 patients treated with ADT and external-beam RT on primary between June 2008 and March 2016. All of them but four were also treated for bone metastases. RT on primary with moderately and extremely hypofractionated regimes started after 10.3 months (3.9–51.7) from ADT. After a median follow-up of 26.4 months (10.3–55.5), 20 patients are alive. Twelve patients showed BF after a median time of 23 months (14.5–104) and CF after a median of 23.6 months (15.3–106.1) from the start of ADT. Three patients became castration resistant, starting a new therapy; median time to castration resistance was 31.03 months (range: 29.9–31.5 months). According to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC), only one patient developed acute grade 3 genitourinary toxicity. No late grade >2 adverse events were observed.ConclusionProstate RT in oligometastatic patients is safe and offers long-lasting local control. When compared to ADT alone, RT on primary seems to improve biochemical control and long-term survival; however, this hypothesis should be investigated in prospective studies. Further research is warranted.

Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts

Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.

Non-melanoma skin cancer treated with high-dose-rate brachytherapy and Valencia applicator in elderly patients: a retrospective case series.

PurposeThe incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. Basal cell carcinoma and squamous cell carcinoma are the two most common subtypes of NMSC. The aim of this study was to estimate tumour control, toxicity, and aesthetic events in elderly patients treated with high-dose-rate (HDR) brachytherapy (BT) using Valencia applicator.Material and methodsFrom January 2012 to May 2015, 57 lesions in 39 elderly eligible patients were enrolled. All the lesions had a diameter ≤ 25 mm (median: 12.5 mm) and a depth ≤ 4 mm. The appropriate Valencia applicator, 2 or 3 cm in diameter was used. The prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) in 48 lesions (group A), and 50 Gy in 10 fractions (5 Gy/fraction) in 9 lesions (group B), delivered 2/3 times a week. The biological effective dose (BED) was 60 Gy and 75 Gy, respectively.ResultsAfter median follow-up of 12 months, 96.25% lesions showed a complete response and only two cases presented partial remission. Radiation Therapy Oncology Group – European Organization for Research and Treatment of Cancer (RTOG/EORTC) G 1-2 acute toxicities were observed in 63.2% of the lesions: 56.3% in group A and 77.7% in group B. Late G1-G2 toxicities was observed in 19.3% of the lesions: 18.8% in group A and 22.2% in group B, respectively. No G3 or higher acute or late toxicities occurred. In 86% of the lesions, an excellent cosmetic result was observed (87.5% in group A and 77.8% in group B). Six lesions had a good cosmetic outcome and only 2.3% presented a fair cosmetic impact.ConclusionsThe treatment of NMSC with HDR-BT using Valencia surface applicator is effective with excellent and good cosmetics results in elderly patients. The hypofractionated course appears effective and no statistical differences were observed between the two groups analysed.

CyberKnife robotic image-guided stereotactic radiotherapy for oligometastic cancer

To evaluate the outcome of robotic CyberKnife (Accuray Inc. Sunnyvale, USA)-based stereotactic radiotherapy (CBK-SRT) for oligometastic cancer patients. Between May 2007 and December 2009, 95patients with a total of 118lesions underwent CBK-SRT (median dose 24Gy in 3fractions). adult patients with limited volume cancer; suitability for SRT but not for other local therapies. Primary diagnoses included breast, lung, head and neck, gastrointestinal and other malignancies. Prostate cancer patients were excluded. Concomitant systemic therapy was given in 40 % of cases and median follow-up was 12months. Toxicity and tumor response were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Scale and Response Evaluation Criteria in Solid Tumors RECIST. Toxicity was rare and observed mainly in patients with comorbidities or uncontrolled cancer. Out of 87evaluable lesions, complete radiological response, partial response, stabilization and progressive disease were observed in 15(17 %), 25(29 %), 34(39 %) and 13(15 %) lesions, respectively. Upon restricting the analysis to lesions treated with CBK-SRT alone (no concomitant therapy), response- and local control (LC) rates remained similar. Actuarial 3-year in-field progression-free survival- (i.e. LC), progression-free survival- (PFS) and overall-survival (OS) rates were67.6,18.4, and 31.2 %, respectively. LC was reduced in cases of early recurrence. OS- and cause-specific survival (CSS) rates were significantly lower in patients treated for visceral lesions. Failures were predominantly out-field. CBK-SRT is a feasible therapeutic approach for oligometastastic cancer patients that provides long-term in-field tumor control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies.

More space, less toxicity: Toxicity report of the first patients with prostate cancer treated in Heidelberg within the SpaceOAR hydrogel study.

e15052 Background: Delivering high radiation dose to prostate while sparing adjacent OARs like the rectum and bladder is challenging. We evaluated acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients within the SpaceOAR Hydrogel study. Methods: Overall, 20 patients with localized prostate cancer recieved definitive radiotherapy by tomotherapy from Oct. 2009 through Jan. 2011. Patients were treated within the SpaceOAR Hydrogelstudy, a prospective, multi-center, open-label trial. Before treatment planning the spacer gel, an absorbable polyethylene glycol (PEG) hydrogel spacer, which extends the space between anterior rectum wall and prostate, was perennially injected between rectum and prostate. Absorption time of the gel is about 6 months. The prescribed dose for the PTV (= [prostate+2/3 seminal vesicle] +margin of 5mm in all directions) was 78 Gy in 39 fractions. During the treatment and at 3, 6 and 12 months after treatment GI and GU toxicity was evaluated utilizing the grading developed by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC). Late rectal toxicity was also detected by using proctoscopy 12 months after the completion of irradiation and scored by using the Vienna rectoscopy score (VRS-Score). Results: The space between rectum and prostate could be increased an average of 10.48mm at base, 9.61mm at mid gland and 9.35mm at the apex. So far, 13 patients have finished irradiation. The incidences of acute Grade 1 GI or GU toxicities at the end of treatment were 7% and 46% in these patients. One patient showed Grade 2 GU toxicity (n=13). After 3 months follow up 27% had Grade 1 GU toxicity but no patient showed GI toxicity (n=11). After 6 month fu Grade 1 GU toxicity decrease to 25% (n=8). After one year (n=4) no patient showed late GI toxicities and 2 patients had Grade I GU toxicity No patient showed any problems of the rectal mucosa in the rectoscopy after 12 months (100% VRS score 0). Conclusions: Use of SpaceOAR Hydrogelis an easy and safe way to reduce toxicity to the rectum. Further evaluations with dose escalation to the prostate or application in other regions are possible.

Use of machine learning methods for prediction of acute toxicity in organs at risk following prostate radiotherapy

The goal of this study is to investigate the advantages of large scale optimization methods vs conventional classification techniques in predicting acute toxicity for urinary bladder and rectum due to prostate irradiation. Clinical and dosimetric data of 321 patients undergoing prostate conformal radiotherapy were recorded. Gastro-intestinal and genito-urinary acute toxicities were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale. Patients were classified in two categories to separate mild (Grade < 2) from severe toxicity levels (Grade > 2). Machine learning methods at different complexity were implemented to predict toxicity as a function of multiple variables. The first approach consisted of a large scale optimization method, based on genetic algorithms (GAs) and artificial neural networks (ANN). The second approach was a binary classifier based on support vector machines (SVM). The ANN and SVM-based solutions showed comparable prediction accuracy, exhibiting an area under the receiver operating characteristic (ROC) curve of 0.7. Different sensitivity and specificity features were measured for the two approaches. The ANN algorithm showed enhanced sensitivity if combined with appropriate classification criteria. The results demonstrate that high sensitivity in toxicity prediction can be achieved with optimized ANNs, that are put forward to represent a valuable support in medical decisions. Future studies will be focused on enlarging the available patient database to increase the reliability of toxicity prediction algorithms and to define optimal classification criteria.

Clinical value of the comprehensive treatment in intermediate and advanced cervical cancer with uterine arterial interventional chemoembolization and radiotherapy

To investigate the long-term curative effect of the radiotherapy combined uterine arterial interventional chemoembolization for cervical cancer. Records of 632 patients with cervical cancer stage II - IVa proved by pathology in Lanzhou Command General Hospital from January 1st, 1999 to August 31st, 2009 were retrospective analysed. One hundred and twenty-six cases of them were treated with radical radiotherapy combined uterine arterial interventional chemoembolization (arterial chemoembolization + radiotherapy group), 506 cases of them were treated with radical radiotherapy only (radiotherapy group); the evaluation of the late radiation injury was done, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) advanced radiation injury criteria. Prognosis and complications were compared between two groups, relative risk factors of radiotherapy complications were identified by method of logistic regression. (1) Survival: the total survival rates of 1-year, 2-year, 5-year and 8-year were 94.4%, 82.3%, 48.8%, 29.1%, respectively. The survival rates of arterial chemoembolization + radiotherapy group were 96.0%, 82.1%, 37.2%, 25.7%, while the survival rates of radiotherapy group were 94.1%, 80.8%, 51.1%, 31.5%, in which there were significant differences between two groups (χ(2) = 0.009, P = 0.993; χ(2) = 0.158, P = 0.691; χ(2) = 11.197, P = 0.001;χ(2) = 9.649, P = 0.002). During the follow-up period, the rate of recurrence and metastasis in arterial chemoembolization + radiotherapy group were 77.0% (97/126), while 73.3% (371/506) in radiotherapy group (χ(2) = 0.705, P = 0.401). (2) Radiotherapy complications and relative risk factors: the total incidence of tardive bladder injury higher than RTOG/EORTC stage II was 5.5% (35/632), while it was 11.1% (14/126) in arterial chemoembolization + radiotherapy group, 4.2% (21/506) in the radiotherapy group (χ(2) = 9.344, P = 0.002). The results of logistic regression showed that the uterine arterial interventional chemoembolization was relative risk factors of the tardive bladder injury (χ(2) = 6.440, OR = 2.869, P = 0.011). Compared with the simple radiotherapy, there are a similar short-term survival rate and significant poor 5-year, 8-year survival rate in the patients treated with the uterine arterial interventional chemoembolization combined with radiotherapy, which also may be strong dangerous factor for the occurrence of tardive bladder injury. The results shown that the uterine arterial interventional chemoembolization do not recommend to be routine adjuvant therapy for the radical radiotherapy of cervical cancer.

The Challenge of Scoring Radiation-induced Lung Toxicity

Aims The increasing use of curative radiation treatment in lung cancer mandates accurate assessment of late lung toxicity. The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring schema combines clinical symptoms and radiological changes and may be confusing. Some have used a scoring scale modified from the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2 scale based on symptoms only. Clinical data using these two different scales have been compared as if they give similar results. The present study compared the outcomes using the two scales in the same group of patients. Materials and methods The medical records and imaging of patients with non-small cell lung cancer who received definitive radiotherapy were reviewed. Eligible patients had a minimum follow-up of 12 months with no clinical signs of local relapse. Radiation-induced lung toxicity was scored using the RTOG/EORTC and the NCI-CTC scales. Results In total, 50 patients were analysed. All patients developed radiographic abnormalities after curative radiotherapy. Grade 0, 1, 2 and 3 toxicity was 0, 28, 49 and 23%, respectively, according to the RTOG/EORTC scale and 86, 7, 7 and 0%, respectively, according to the NCI-CTC scale, showing that the inclusion of radiographic abnormalities changes and significantly upgrades the toxicity scores. Conclusion After curative radiotherapy, all patients presented some radiographic abnormality. There was no correlation with lung symptoms. The assessment of radiation-induced lung toxicity differs depending on the scoring system used. Comparison of reports that use different scoring scales should be made with caution. A scale based on symptoms only, such as the NCI-CTC scale, may be more appropriate to evaluate long-term toxicity after curative radiotherapy for lung cancer.

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

Final report of RTOG 9610, a multi‐institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck

Our objectives were to determine the incidence of acute and late toxicities and to estimate the 2-year overall survival for patients treated with reirradiation and chemotherapy for unresectable squamous cell carcinoma of the head and neck (SCCHN). Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field were eligible. Four weekly cycles of 5-fluorouracil 300 mg/m2 IV bolus and hydroxyurea 1.5 g by mouth were used with 60 Gy at 1.5 Gy twice-daily fractions. Toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Seventy-nine of the 86 patients enrolled were analyzable. The worst acute toxicity was grade 4 in 17.7% and grade 5 in 7.6%. Grade 3 and 4 late toxicities were found in 19.4% and 3.0%, respectively. The estimated cumulative incidence of grade 3 to 4 late effects occurring at >1 year was 9.4% (95% confidence interval [CI]: 0, 19.7) at 2 and 5 years. The 2- and 5-year cumulative incidence for grade 4 toxicity was 3.1% (95% CI: 0, 9.3). The estimated 2- and 5-year survival rates were 15.2% (95% CI: 7.3, 23.1) and 3.8% (95% CI: 0.8, 8.0), respectively. Patients who entered the study at >1 year from initial radiotherapy (RT) had better survival than did those who were <1 year from prior RT (median survival, 9.8 months vs 5.8 months; p = .036). No correlation was detected between dose received and overall survival. Three patients were alive at 5 years. This is the first prospective multi-institutional trial testing reirradiation plus chemotherapy for recurrent or second SCCHN. The approach is feasible with acceptable acute and late effects. The results serve as a benchmark for ongoing RTOG trials.

Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute

Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III in 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed.

Concurrent cisplatin, infusional fluorouracil, and conventionally fractionated radiation therapy in head and neck cancer: dose-limiting mucosal toxicity.

After a preliminary dose-finding study involving 12 patients with advanced or locally recurrent head and neck cancer, 27 patients were treated on a phase II protocol, using fluorouracil 350 mg/m2/d by continuous intravenous (IV) infusion over 5 days, followed on the sixth day by a 2-hour IV infusion of cisplatin 50 mg/m2, administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 Gy, using 2 Gy daily fractions. Eight of these 27 patients had American Joint Committee on Cancer Staging (AJCC) stage III disease, and 12 had stage IV disease. Four had recurrent disease after surgery. Three-year follow-up is now available. Twenty-one (77.8%) remitted completely following treatment, and 11 remain free of local and regional relapse at 3 years. Four have developed systemic metastases. Following successful salvage treatment in two cases, estimated determinate survival at 3 years is 64%. Acute toxicity was manageable with this regime. Eleven instances of grade 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) mucositis were observed, which caused interruptions to radiotherapy in only four cases. No late sequelae have so far been recorded. It is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional "cures" than would have been expected following conventional radiotherapy alone in this group of patients. The use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic.