Acute Radiation Therapy Oncology Group Research Articles

Correlation of oral mucositis with timing of radiation in head and neck cancer - A prospective randomized study on chronoradiotherapy

Context: Study to reduce oral mucositis using chronoradiotherapy. Aims: This study aims to assess and compare oral mucositis and weight loss between two groups of patients on radiation-morning and evening group. Settings and Design: Prospective randomized study. Subjects and Methods: Sixty-four head and neck cancer patients were enrolled in the study. They were allotted into two arms, i.e., morning-arm A and evening-arm B using randomization. Baseline weight was recorded for all the patients. Weight and the grade of mucositis were recorded weekly during radiotherapy (RT) and at 2nd and 6th week post treatment in both the arms. Mucositis was graded based on the Radiation Therapy Oncology Group acute radiation morbidity scoring criteria. Statistical Analysis Used: The analysis of different grades and the incidence of mucositis at weekly intervals and follow-up were compared using Chi-square test. Weight loss was compared using t-test. Results: The progression of mucositis to higher grades was delayed by a week in the morning arm compared to the evening arm. Arm A (morning arm) developed Grade 3 mucositis in 21.9% patients versus 25% in the arm B (evening arm). Conclusions: Circadian rhythm has an impact on mucositis trending toward morning RT being less toxic with delayed progression and thereby decreased weight loss and better tolerance to radiation.

Ultrahypofractionation Should be a Standard of Care Option for Intermediate-Risk Prostate Cancer

Ultrahypofractionation Should be a Standard of Care Option for Intermediate-Risk Prostate Cancer

Early Results of Extreme Hypofractionation Using Stereotactic Body Radiation Therapy for High-risk, Very High-risk and Node-positive Prostate Cancer

AimsStereotactic body radiotherapy (SBRT) in low- and intermediate-risk prostate cancer has shown encouraging results. However, its use in high-risk patients is limited due to lack of data regarding adequate radiotherapy dose, need for pelvic nodal treatment and androgen deprivation therapy. Herein we report our experience of SBRT in this subgroup. Materials and methodsAnalysis of a prospectively maintained database of 68 consecutive patients of the National Comprehensive Cancer Network (NCCN) high-risk, very high-risk and node-positive adenocarcinoma prostate treated with SBRT was undertaken. All patients were treated with rotational intensity-modulated radiotherapy with daily image guidance. The dose delivered to the prostate and gross node was 35–37.5 Gy in 5 alternate day fractions. Node-positive patients received 25 Gy to pelvic nodal regions until the common iliac nodes. Treatment was delivered in 7–10 days. All patients received long-term androgen deprivation therapy (79% medical and 21% surgical). ResultsMost patients (65%) had a Gleason score ≥ 8. The median prostate-specific antigen was 42. Twenty patients were high risk (30%), 11 (16%) very high risk and 37 (54%) node positive. No acute Radiation Therapy Oncology Group grade ≥ 3 genitourinary or gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicity were 12% and 3%, respectively. Late grade 3 genitourinary and gastrointestinal toxicity was 3% and 0%, respectively. There was no increase in acute or late gastrointestinal toxicity with prophylactic pelvic nodal radiotherapy. Prior transurethral resection of prostate (n = 11) did not increase toxicity. At a median follow-up of 18 months, 97% patients were alive and 94% were biochemically controlled. ConclusionSBRT is safe in the treatment of high-risk, very high-risk and node-positive prostate cancer, even with prophylactic pelvic radiotherapy or prior transurethral resection of prostate. Longer follow-up is required to determine efficacy.

A Phase 2 Study of 2 Weeks of Adjuvant Whole Breast/Chest Wall and/or Regional Nodal Radiation Therapy for Patients With Breast Cancer

To report the results in terms of feasibility and early toxicity of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiation therapy for patients with breast cancer. From June 2013 to October 2014, 50 patients with breast cancer after mastectomy or after breast conservation surgery (BCS) were prospectively included. The institutional ethics committee approved the study, which was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier no. NCT02460744). Treatment planning was performed using a simulator with 2 tangential fields to the breast/chest wall and an incident field to the supraclavicular fossa. The radiation dose delivered was 34Gy in 10 fractions within 2weeks, followed by a boost of 10Gy in 5 fractions within 1week for patients who underwent BCS. Acute skin toxicities were recorded during and after treatment according to the Radiation Therapy Oncology Group acute radiation toxicity scoring criteria. The primary objective was to obtain estimates of the acute toxicity rates and cosmetic outcomes that could be used to design a subsequent phase III comparative study. Acute skin and late toxicities were recorded during and after treatment. Cosmetic outcomes were assessed before and after treatment and during the regular follow-up period. A cost/benefit analysis was also performed and compared with that for standard treatment of 35Gy in 15 fractions within 3weeks. The median follow-up was 39months (range 14-48). The mean age was 51years (range 26-75). A left-sided tumor was present in 25 patients (50%). Total mastectomy with axillary clearance was performed in 40 (80%) and BCS in 10 (20%) patients. Acute grade 2 and 3 skin toxicity was seen in 16 (32%) and 1 (2%) patient, respectively. In the BCS patients, grade 2 skin and subcutaneous toxicity was seen in 2 (20%) and 1 (10%) patient, respectively. Grade 2 edema was seen in 1 patient (10%). The cosmesis was excellent or good in 8 (80%) and fair or poor in 2 (20%) patients. The cost/benefit analysis revealed significantly less financial burden on the patients with 2weeks of treatment. Disease-free and overall survival at 3years was 94% and 96%, respectively. Hypofractionated radiation therapy within 2weeks appears to be feasible for patients with breast cancer and was associated with acute and late skin toxicity profiles similar to those observed with 3weeks of treatment. The financial burden on the patient and family could be reduced with 2weeks of treatment. Long-term follow-up data and a prospective comparative study are needed to strengthen these results. Hypofractionation might help radiation centers worldwide to meet the increasing need for radiation for breast cancer, especially in developing countries where resources are limited and patients must travel long distances for treatment.

Acute toxicity of concomitant boost radiation therapy by volumetric-modulated arc therapy in head and neck cancers

AbstractIntroductionVolumetric-modulated arc therapy (VMAT) is an advanced form of intensity-modulated radiation therapy that reduces treatment time without compromising plan quality. This study assessed acute toxicities in patients having carcinomas of oropharynx, larynx and hypopharynx treated with concomitant boost radiation therapy by VMAT.Materials and methodsIn this study, 30 patients of stages II–IVA disease were treated with concomitant boost radiation therapy using VMAT and those with stages III and IV also received concurrent chemotherapy with cisplatin 100 mg/m2 weekly thrice for two cycles. The total dose was 68·4 Gy/40 fractions/5.5 weeks (1·8 Gy/fraction/day to the large field for 28 fractions +1·5 Gy/fraction/day to boost field for the last 12 days of treatment). Radiation Therapy Oncology Group acute radiation morbidity scoring criteria was used to grade acute effects.ResultsAll patients completed scheduled treatment with median duration of 44 days. No grade 4 skin and mucosal toxicities were observed; grade 3 skin and mucosal toxicities seen in six (20%) and eight (26·67%) patients, respectively; grade 3 dysphagia and laryngeal toxicity in eight (26·67%) and three (10%) patients, respectively; two patients had grade 4 laryngeal toxicity. No grade 3 or grade 4 haematological toxicities were seen.ConclusionVMAT-based concomitant boost radiation therapy allows for dose escalation with good patient tolerance by limiting acute toxicities.

The effects of recombinant human granulocyte colony-stimulating factor mouthwash on radiotherapy-induced oral mucositis in locally advanced nasopharyngeal carcinoma patients.

Acute oral mucositis is a common complication of radiotherapy for nasopharyngeal carcinoma (NPC) patients. The aim of the study was to observe the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on radiotherapy-induced oral mucositis in locally advanced NPC patients. The study involved 64 locally advanced NPC patients that were randomly allocated to receive either rhG-CSF mouthwash (2 μg/mL rhG-CSF; group A, n = 34) or a compounded mouth rinse (10 μg/mL vitamin B12, 0.48 mg/mL gentamicin and 0.04 mg/mL dexamethasone in saline; group B, n = 30) during radiotherapy. Both mouthwashes were used 6 times daily at the onset of oral mucositis, and the treatments continued until the end of all intensity-modulated radiotherapy sessions. Oral mucositis was graded according to the Radiation Therapy Oncology Group acute radiation morbidity scoring criteria. A visual analog scale was used to assess peak mouth pain once a week, and the duration of oral mucositis was recorded. In comparison with group B, the patients in group A had a significantly lower incidence of oral mucositis of grade 3 or above (38.2% vs 66.7%, p < 0.05) and less peak mucosal pain in the 5th, 6th and 7th weeks of radiotherapy (p < 0.05). group A patients also had shorter durations of oral mucositis (35.1 days vs 39.4 days, p < 0.05) and lower peak swallowing function scores (p < 0.05). The rhG-CSF mouthwash may be more effective than the compounded mouth rinse in preventing and treating radiotherapy-induced mucositis and mucositis-related pain, and thus improving the quality of life for locally advanced NPC patients. These effects should be further investigated in a prospective controlled study.

Evaluation of the Effects of Prostate Radiation Therapy on Occludin Expression and Ultrasonography Characteristics of the Bladder

To evaluate the effects of radiation dose in prostate radiation therapy (RT) on occludin expression and ultrasonography characteristics of the bladder. Urine samples of 64 prostate RT patients were collected before, at regular intervals during, and 3months after RT. Occludin expression analysis was performed, and bladder wall echogenicity and echotexture were investigated by ultrasound and the gray-scale histogram analysis method. The bladder equivalent uniform dose (EUD) was derived from individually produced dose treatment plan for each patient. Clinical scoring for bladder-specific symptoms was done using the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria Scale. Thirty patients (47%) experienced at least 1 of the studied bladder symptoms (grade ≥1 endpoints), including urinary pain, frequency, urgency, straining, incontinence, hematuria, dysuria, and nocturia. For these patients there were significant changes in urine occludin levels after starting the treatment compared with the baseline urine samples (P=.023). The mean bladder EUD that caused a significant change in occludin level, which occurred after the 15th RT session, was 26.9Gy (range, 13.2-36.5Gy, P=.020). In all patients a significant reduction in bladder echogenicity (P=.0137) and a significant change in its echotexture (P=.047) was found after the 10th RT session, after which the EUD to the bladder reached 17.9Gy (range, 8.8-24.3Gy). Significant changes in occludin expression level and bladder wall echogenicity and echotexture occurred during prostate RT. Our findings suggest that a significant reduction in bladder echogenicity and increase in occludin expression during treatment can be associated with acute urinary complications.

Phase I Clinical Trial of Everolimus Combined with Trimodality Therapy in Patients with Muscle-Invasive Bladder Cancer.

Background: Local control following trimodality therapy (TMT) for muscle-invasive bladder cancer (MIBC) requires further optimization.Objective: Evaluating the biologic endpoint, feasibility, and toxicity of integrating everolimus to TMT in patients with MIBC.Methods: This was a phase I trial in patients with MIBC who were not surgical candidates or who refused cystectomy. Following maximal transurethral tumor resection, patients were treated by radiotherapy (50 Gy/20 fractions), gemcitabine (100 mg/m2/weekly) and escalating doses of everolimus (2.5–5.0 mg/day). Everolimus was given daily for one month prior to radiation, during treatment, and one month post-radiation. Toxicity assessment followed the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. Biologic endpoint with downregulation of phospho-S6 (pS6) was assessed using immunohistochemistry. Local response was evaluated with imaging and bladder biopsy post-therapy.Results: 10 patients were recruited; 8 males, 2 females. Median age was 78 years (range: 63–85). Four patients entered everolimus 2.5 mg cohort. Six other patients entered everolimus 5.0 mg cohort. Toxicities were encountered in 2 patients (Grade I), 6 patients (Grade II), 9 patients (Grade III) and 1 patient (Grade IV), with some experiencing more than one toxicity. Most Grade III and IV toxicities were encountered from everolimus alone prior to combination testing. Trial was terminated early due to toxicity. Interestingly, 6/10 patients (60%) achieved a complete response with negative post-treatment biopsies. Significant decrease of pS6 was demonstrated post-therapy (p = 0.03).Conclusions: Although combining everolimus with TMT achieved a biological endpoint and complete response in a significant number of patients with MIBC and negative prognostic factors, it was associated with unacceptable increased toxicity.

Use of Stereotactic Radiosurgery in Elderly and Very Elderly Patients With Brain Metastases to Limit Toxicity Associated With Whole Brain Radiation Therapy

We evaluated the toxicity associated with stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) in elderly and very elderly patients with brain metastases, as the role of SRS in geriatric patients who would traditionally receive WBRT is unclear. We conducted a retrospective review of elderly patients (aged 70-79years) and very elderly patients (aged ≥80years) with brain metastases who underwent RT from 2010 to 2015 at Johns Hopkins Hospital. Patients received either upfront WBRT or SRS for metastatic solid malignancies, excluding small cell lung cancer. Acute central nervous system toxicity within 3months of RT was graded using the Radiation Therapy Oncology Group acute radiation central nervous system morbidity scale. The toxicity data between age groups and treatment modalities were analyzed using Fisher's exact test and multivariate logistic regression analysis. Kaplan-Meier curves were used to estimate the median overall survival, and the Cox proportion hazard model was used for multivariate analysis. A total of 811 brain metastases received RT in 119 geriatric patients. The median overall survival from the diagnosis of brain metastases was 4.3months for the patients undergoing WBRT and 14.4months for the patients undergoing SRS. On multivariate analysis, WBRT was associated with worse overall survival in this cohort of geriatric patients (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.9-7.0, P<.0001) and age ≥80years was not. WBRT was associated with significantly greater rates of any grade 1 to 4 toxicity (OR 7.5, 95% CI 1.6-33.3, P=.009) and grade 2 to 4 toxicity (OR 2.8, 95% CI 1.0-8.1, P=.047) on multivariate analysis. Elderly and very elderly patients did not have significantly different statistically acute toxicity rates when stratified by age. WBRT was associated with increased toxicity compared with SRS in elderly and very elderly patients with brain metastases. SRS, rather than WBRT, should be prospectively evaluated in geriatric patients with the goal of minimizing treatment-related toxicity.

Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model.

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID (P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy.

Feasibility of Concurrent Chemoradiation in Cervical Cancer Patients From Rural Background

BackgroundConcurrent chemoradiation causes toxicities such as enteritis, hematologic toxicities which may lead to treatment interruptions, and therefore inferior outcomes. Adequate supportive care is very important to complete the scheduled protocol. Most of our patients are from rural background with a heterogeneous social background (nutrition and social support). There is paucity of literature to evaluate the tolerance of this intense treatment in these groups of patients, and hence, this study was undertaken. MethodsIn this observational study, 30 rural women having carcinoma cervix treated with concurrent chemoradiation between January and July 2013 were reviewed retrospectively. They were assessed weekly for dyselectrolytemia, enteritis, and hematologic toxicity using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. Treatment gaps along with reasons were recorded and correlated. ResultsMedian age of patients was 54 years. Of the patients, 43.3% were International Federation of Gynecology and Obstetrics stage II and 46.7% stage III. Grade 3 enteritis was seen in 7 of 30 patients (23.3%). None (0%) had grade 3 or higher hematologic toxicity. Dyselectrolytemia–hyponatremia (46.66%), hypokalemia (26.66%), hypocalcemia (6.66%), and hypomagnesemia (10%) were noted. Two of thirty patients (6.66%) received the planned 5 cycles, cisplatin 40 mg/m2 weekly. There were treatment interruptions in radiation in 6 (20%) and treatment delays in chemotherapy in 10 (33.33%) patients. ConclusionConcurrent chemoradiation for patients from rural areas is associated with higher acute toxicities. Regular monitoring for enteritis and dyselectrolytemias and timely intervention can help improve compliance and decrease treatment interruptions and thereby achieve the optimum treatment outcome.

Decline in acute urinary toxicity: A long-term study in 2011 patients with prostate brachytherapy within a provincial institution

To determine whether acute urinary toxicity rates improve with the overall experience of a large prostate brachytherapy program. From 1998 to 2009, 2937 patients were treated with prostate brachytherapy at the British Columbia Cancer Agency. Baseline patient, treatment, and implant factors were recorded prospectively. Acute urinary toxicity data were prospectively recorded at baseline and each follow-up visit. Patients with ≥2 years of follow-up data were grouped into cohorts of 500 for analysis. Two thousand eleven patients met the above criteria. Acute urinary retention (AUR) in the acute period (within 6 months of implant) occurred in 9.1% of patients overall and was prolonged (catheterization >20 days) in 3.4%. Both overall AUR and prolonged AUR decreased across implant cohorts (p ≤ 0.001 in both cases). Overall acute Radiation Therapy Oncology Group (RTOG) Grades 0 and 1 urinary toxicity rate was 57.5% and RTOG Grades 2 and 3 urinary toxicity rates were 34.3% and 8.1%, respectively. Acute toxicity improved over time for both RTOG Grades ≥2 and ≥3 toxicity (p < 0.0001). International prostate symptom score resolution to baseline was achieved in 80.5% of patients with a median time of 12.2 months. Acute AUR and RTOG urinary toxicity rates continue to decline with the increasing experience of our provincial prostate brachytherapy program, despite its expansion to new centers and addition of members. This is likely due to better patient selection, refinement in treatment planning and implantation technique, and mentorship and training process.

Spine Radiosurgery: A Dosimetric Analysis in 124 Patients Who Received 18 Gy

To define the safely tolerated doses to organs at risk (OARs) adjacent to the target volume (TV) of spine radiosurgery (SRS) with 18-Gy in a single fraction. A total of 124 patient cases with 165 spine metastases were reviewed. An 18-Gy single-fraction regimen was prescribed to the 90% isodose line encompassing the TV. A constraint of 10 Gy to 10% of the spinal cord outlined 6 mm above and below the TV was used. Dosimetric data to OARs were analyzed. A total of 124 patients (100%) were followed-up, and median follow-up time was 7 months (1-50 months). Symptoms and local control were achieved in 114 patients (92%). Acute Radiation Therapy Oncology Group (RTOG) grade 1 oral mucositis occurred in 11 of 11 (100%) patients at risk for oropharyngeal toxicity after cervical spine treatment. There were no RTOG grade 2-4 acute or late complications. Median TV was 43.2 cc (5.3-175.4 cc) and 90% of the TV received median dose of 19 Gy (17-19.8 Gy). Median (range) of spinal cord maximum dose (Dmax), dose to spinal cord 0.35 cc (Dsc0.35), and cord volume receiving 10 Gy (Vsc10) were 13.8 Gy (5.4-21 Gy), 8.9 Gy (2.6-11.4 Gy) and 0.33 cc (0-1.6 cc), respectively. Other OARs were evaluated when in proximity to the TV. Esophagus (n=58), trachea (n=28), oropharynx (n=11), and kidneys (n=34) received median (range) V10 and V15 of 3.1 cc (0-5.8 cc) and 1.2 cc (0-2.9 cc), 2.8 cc (0-4.9 cc), and 0.8 cc (0-2.1 cc), 3.4 cc (0-6.2 cc) and 1.6 cc (0-3.2 cc), 0.3 cc (0-0.8 cc) and 0.08 cc (0-0.1 cc), respectively. Cord Dmax of 14 Gy and D0.35 of 10 Gy are safe dose constraints for 18-Gy single-fraction SRS. Esophagus V10 of 3 cc and V15 of 1 cc, trachea V10 of 3 cc, and V15 of 1 cc, oropharynx V10 of 3.5 cc and V15 of 1.5 cc, kidney V10 of 0.3 cc, and V15 of 0.1 cc are planning guidelines when these OARs are in proximity to the TV.

Toxicity after 125I prostate brachytherapy in patients with inflammatory bowel disease

To determine gastrointestinal (GI) toxicity after (125)I prostate brachytherapy in patients with inflammatory bowel disease (IBD). We retrospectively reviewed 13 patients diagnosed with IBD from a cohort of over 3200 patients with low- to intermediate-risk prostate cancer treated with (125)I brachytherapy (144Gy). Acute (i.e. <12 months) and late lower GI toxicity after brachytherapy using the Radiation Therapy Oncology Group (RTOG) grading system was assessed. Possible factors (e.g. patient, treatment, dosimetry, and characteristics of IBD) influencing GI toxicity were assessed. Median followup was 4.2 years. Ten patients had ulcerative colitis (UC) and 3 had Crohn's disease. Seven patients with UC had known involvement of the rectum. Acute RTOG GI Grade 0, 1, 2, 3, 4 toxicity was seen in 7, 1, 2, 2, 1 patients, respectively. The corresponding late RTOG GI toxicity was seen in 7, 1, 3, 1, 1 patients, respectively. Two patients required major surgery. All patients with severe GI toxicity (i.e., Grade≥3) had UC with disease involving the rectum and underwent endoscopic biopsies of the rectum within 3 months after the implant. There was no clear association with other factors with toxicity. Twenty-three percent and 15% patients with IBD experienced Grade 3 or higher acute and late GI toxicity, respectively, after brachytherapy. Prostate brachytherapy should be used with great caution or avoided, particularly for men with active IBD involving the rectum. Biopsies of the rectum after brachytherapy should be avoided as it may lead to ulceration.

Rectal toxicity and rectal dosimetry in low-dose-rate 125I permanent prostate implants: A long-term study in 1006 patients

ObjectiveTo describe the acute and late rectal toxicity in 1006 prostate brachytherapy patients implanted 1998–2003. To determine whether rectal dose–volume histogram as well as patient and treatment factors were associated with rectal toxicity. Methods and materialsMedian followup was 60.7 months. Rectal dosimetry was calculated as dose–volume histogram of the rectum using Day 28 CT-based dosimetry and expressed as volume of the rectum in cc receiving 50%, 100%, and 150% of the prescription dose (VR50cc, VR100cc, and VR150cc, respectively). Univariate and multivariate analyses were performed to examine the influence of patient, implant, dosimetry, and learning curve factors on the development of acute and late toxicities using a modified Radiation Therapy Oncology Group (RTOG) scale. Acute toxicity was analyzed using logistic regression and late toxicity using Cox proportional hazards regression. Analysis of variance was used to examine the association between rectal toxicity and rectal dose. ResultsRectal dosimetry in 93.5% and rectal toxicity in 96.2% have been recorded. Median VR100=1.05cc. Late RTOG Grades 0, 1, 2, 3, and 4 were recorded in 68%, 23%, 7.3%, 0.9%, and 0.2% patients, respectively. On multivariate analysis, acute RTOG ≥2 rectal toxicity was associated with urinary retention (p=0.036) and learning curve (p=0.015); late RTOG ≥2 was associated with the presence of acute toxicity (p=0.0074), higher VR100 (p=0.030) and learning curve (p=0.027). ConclusionsLate rectal RTOG ≥2 rectal toxicity in this cohort was 8%. Increased VR100, presence of acute rectal toxicity, and learning curve were associated with higher rate of late RTOG ≥2 toxicity. Severe late rectal toxicity after prostate brachytherapy was rare.

Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. Ina large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR= 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR= 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR= 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR= 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR= 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR= 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Knowledge of these predictors easily collected in a clinical setting could help tailoring therapies to reduce toxicities among patients treated with RT for HNC.

Treatment of recurrent high grade gliomas with hypofractionated stereotactic image-guided helical tomotherapy

ObjectiveSalvage treatment of high grade gliomas that progress after standard therapy of resection and adjuvant chemoradiation therapy includes repeat surgical resection, second line chemotherapy, re-irradiation, or often a combination of the above. We present a series on patients treated with hypofractionated stereotactic image-guided helical tomotherapy and discuss the efficacy of this new technology in the treatment of high grade gliomas. Materials and methodsBetween June 2005 and August of 2008, eight patients with recurrent high grade gliomas were treated with salvage radiation therapy using hypofractionated stereotactic image-guided helical tomotherapy after image documentation of disease progression. Median age was 48.5 years with 4 females and 4 males. Median KPS at time of treatment was 65. All patients had either Grade III or IV gliomas at time of treatment with previous history of involved field fractionated radiotherapy. Median total dose given was 2500cGy in 500cGy fractions. ResultsThe median planning target volume was 69.5cm3. Five of the eight patients were alive at the time of last follow-up with a median survival of 7.6 months. Radiographic documented control was seen in six of the eight patients with median local control of 4.6 months. Acute Radiation Therapy Oncology Group (RTOG) toxicity scores measured zero in all patients with only one patient requiring a reoperation following treatment. ConclusionsHypofractionated stereotactic image-guided helical tomotherapy provides an alternative to other stereotactic radiation therapy and radiosurgery options for treatment of recurrent high grade gliomas.

Intensity-modulated Radiotherapy Allows Escalation of the Radiation Dose to the Pelvic Lymph Nodes in Patients with Locally Advanced Prostate Cancer: Preliminary Results of a Phase I Dose Escalation Study

Aim Pelvic irradiation in addition to prostate irradiation may improve outcome in locally advanced prostate cancer, but is associated with dose-limiting bowel toxicity. We report the preliminary results of a dose escalation study using intensity-modulated radiotherapy. Materials and methods Eligible patients had high-risk (T3, Gleason ≥8 or prostate-specific antigen ≥20 ng/ml) or lymph node-positive disease. Intensity-modulated radiotherapy was inverse planned giving 70 Gy/35 fractions to the prostate and 50 Gy/55 Gy/60 Gy in sequential cohorts to the pelvis with a 5 Gy boost to positive lymph nodes. Acute and late toxicity were recorded with Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue - Subjective Objective Management LENT-SOM scales. Neoadjuvant androgen suppression was given for 3 years. This report concerns the 50 and 55 Gy cohorts. Results Seventy-nine men were recruited (25 to 50 Gy/54 to 55 Gy) with a median follow-up of 2 years. Patients were divided into two groups according to the total bowel volume outlined (median 450 cm 3). Acute RTOG (≥2) bowel toxicity was 40 and 50% for the 50 and 55 Gy groups and 38 and 51% for bowel volume <450 cm 3 and ≥450 cm 3, respectively, suggesting both volume and dose relationships for acute effects. Late RTOG diarrhoea ≥grade 2 was only seen with bowel volume ≥450 cm 3, but no dose effect was apparent (12%/50 Gy and 10%/55 Gy). LENT-SOM bowel ≥grade 2 toxicity occurred in 22%/50 Gy and 15%/55 Gy. Only one patient had grade 3 toxicity. A dose volume histogram analysis showed increased late RTOG diarrhoea ≥grade 2 with larger bowel volume irradiated, significant for BV40 >124 cm 3 ( P = 0.04), BV45 >71 cm 3 ( P = 0.03) and BV60 >2 cm 3 ( P = 0.01). Conclusions Acute and late bowel toxicity was acceptably low using a pelvic dose of up to 55 Gy over 7 weeks. Both relate to total pelvic bowel volume and dose volume constraints have been defined.

High-dose intensity-modulated radiotherapy as primary therapy for prostate cancer: Report on dosimetry aspects and acute toxicity in the Indian scenario

Dose escalation improves local control in prostate cancer. In this study we assess the feasibility of dose escalation to prostate and / or seminal vesicles to 76 Gy with intensity-modulated radiotherapy (IMRT); report data on dosimetry and acute toxicity in 40 patients at P. D. Hinduja National Hospital and Medical Research Center, Mumbai. In the period from May 2006 to September 2008, 40 consecutive patients with localized prostate adenocarcinoma (T1- 3 N0) were definitively treated with IMRT to a dose of 76 Gy / 38 fractions. Patients were seen on a weekly basis during treatment, and one month (M1) and three months (M3) thereafter. The radiation therapy oncology group (RTOG) toxicity scale was used to evaluate acute gastrointestinal (GI) and genitourinary (GU) toxicities. Additional symptoms such as rectal blood loss, urgency, dysuria, urinary frequency, nocturia, incontinence were scored as well. All 40 patients completed treatment successfully. Acute RTOG Grade 1 and Grade 2 GI toxicities were noted in 47.5% (19 patients) and 12.5% (five patients) respectively, leaving 40% (16 patients) free of any acute toxicity. Thirty-six (90%) and four patients (10%) had Grade 0-1 and Grade 2 acute RTOG-scaled GU toxicity respectively. There was no Grade 3 or higher GI / GU toxicity. The escalated dose of 76 Gy to the prostate with IMRT was very well tolerated by all our patients with acceptable acute GU and GI toxicity, thereby, establishing the feasibility of dose escalation in the Indian scenario.

Toxicity report of a phase 1/2 dose‐escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy

The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system). This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity. Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade > or =3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group-European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images. The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction.