Late Radiation Therapy Oncology Group Research Articles

Primary radiation therapy for advanced-stage laryngeal cancer: A laryngo-esophageal dysfunction disease-free survival.

To evaluate the outcomes of advanced-stage laryngeal squamous cell carcinoma (SCC) patients treated with functional-preservation strategy with a specific focus on laryngo-esophageal dysfunction disease-free survival (LEDDFS). A retrospective review was conducted of stage III-IVB laryngeal SCC patients who were treated with curative-intent radiotherapy (RT) (2007-2018). Patients were preferentially managed with upfront chemoradiation (CCRT); except for those with cN2-3, cT4, or large volume cT3 (induction chemotherapy followed by RT or CCRT is an option), and those who were unfit or declined chemotherapy (received altered RT). The primary endpoint was 3-year LEDDFS, and secondary endpoints were 3-year local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), disease-free survival (DFS), and acute and late toxicities. Cox proportional hazard tests were used for multivariable analysis (MVA). A total of 213 cases were included. With a median follow-up of 37 months, the 3-year LEDDFS was 50%, while the 3-year OS, DFS, LF, RF, and DM were 81%, 74%, 9%, 5%, and 7%, respectively. On MVA, cT4-category was the only predictor of inferior LEDDFS (HR: 0.47, [95% CI: 0.29-0.74], p < .01). The most common grade ≥ 3 acute and late radiation therapy oncology group (RTOG) toxicity were esophageal toxicity: 16.7% and 29.6%, respectively. Primary RT resulted in favorable oncologic and functional outcomes in only half of the advanced-stage laryngeal cancer patients. Future clinical trials are required to investigate further treatment options aiming to improve the oncologic and maintain functional outcomes with utilization of LEDDFS as the primary endpoint. 4.

Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: 5-Year Efficacy and Toxicity in the DELINEATE Trial

Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy. DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years. Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C). The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer

AimsThe safety and efficacy of stereotactic body radiotherapy (SBRT) in localised prostate cancer are now established through phase III randomised trials. Its utility in node-positive prostate cancer is restricted due to a lack of controlled studies specifically addressing this subgroup. Herein we report the safety and efficacy of SBRT in this subgroup. Materials and methodsIn total, 60 patients treated with SBRT to prostate and pelvis were analysed. All patients received neoadjuvant androgen deprivation therapy for at least 6 months and long-term adjuvant hormonal therapy (70% medical and 30% surgical). All patients were treated with daily image-guided rotational intensity-modulated radiotherapy. The dose delivered to the prostate and gross node was 35–37.5 Gy and 25 Gy in five fractions to the elective pelvic nodal region on alternate days. Acute and late toxicities were graded as per Radiation Therapy Oncology Group common toxicity criteria. ResultsForty-one (68%) patients had a Gleason score ≥8. The median prostate-specific antigen level at diagnosis was 39 ng/ml. Twenty (33%) patients had common iliac nodal uptake on initial prostate-specific membrane antigen positron emission tomography-computed tomography. After the median follow-up of 30 months, no acute or late Radiation Therapy Oncology Group grade ≥3 gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicities were 8.3% and 11.7%, respectively. Late grade 2 genitourinary and gastrointestinal toxicities were 3.3% and 8.3%, respectively. Late grade 3 genitourinary toxicity was seen in two (3.3%) patients. Three-year overall survival and biochemical failure-free survival was 89% and 77%, respectively. ConclusionSBRT to the prostate and pelvis is safe and efficacious in node-positive prostate cancer even with common iliac nodal involvement (stage M1a).

Outcomes and Tolerability of Definitive and Preoperative Chemoradiation in Elderly Patients With Esophageal Cancer: A Retrospective Institutional Review

PurposeOur purpose was to report outcomes of elderly patients who underwent definitive treatment involving radiation therapy for esophageal cancer at our institution. Methods and MaterialsWe performed a retrospective review of patients aged ≥75 years with esophageal cancer treated with definitive radiation therapy (≥45 Gy) at our institution from 1997 to 2019. Acute and late Radiation Therapy Oncology Group grade 3+ toxicities were recorded. Survival was estimated using the Kaplan-Meier method. ResultsOf the 89 patients included, median age was 80 and 78% were male. Median adjusted Charlson Comorbidity Index and Karnofsky Performance Status were 5 (3-12) and 80 (50-100), respectively. The majority of cancers were adenocarcinoma (58%), distal (67%), and stage III (62%). Fifty-eight percent underwent definitive chemoradiotherapy, and one-third underwent preoperative intent chemoradiotherapy. Median prescribed dose was 50 Gy (45-66 Gy), and intensity modulated radiation therapy was used in 76%. Eighty-five percent completed the radiation therapy course. Among these, 20% had radiation therapy breaks. For those receiving concurrent chemotherapy, 37% had a dose reduction and 39.5% had a break/cycle reduction. Acute grade 3+ toxicity was 22%, with 2% grade 5 toxicity. Twenty-one of the 29 patients (72%) treated with preoperative intent underwent surgery. There were no deaths 90 days postoperatively. For patients who underwent surgery, 1- and 2-year overall survival were 95% and 84%. For those who did not undergo surgery, 1- and 2-year overall survival were 70% and 52%. ConclusionsThere is a role for aggressive radiation therapy in well-selected elderly patients with esophageal cancer. However, optimization of supportive care, chemotherapy regimens, radiation therapy dose/fractionation, and surgical indications are needed to reduce toxicity.

Stereotactic Body Radiation Therapy (SBRT) for Intermediate and High-Risk Prostate Cancer: Early Adoption in a Community Hospital Setting

The primary objective of the current study is to report long-term survival (OS), biochemical relapse free survival (BRFS) and toxicity following SBRT for men with intermediate and high risk prostate cancer in a community hospital setting. Ninety-eight consecutive men treated with SBRT between 2007 and 2015 were retrospectively stratified by NCCN risk groups, including favorable intermediate (n=43), unfavorable intermediate (n=44) and high risk (n=11). Additional factors for analysis include Gleason Score (GS), clinical stage, initial PSA, % of cores positive (<50% vs >50%), PTV dose (35Gy vs 36.25Gy vs 37.5Gy), use of ADT, race, and age. Biochemical failure was assessed using the Phoenix nadir +2 definition. Toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) criteria with modification for bowel and bladder function. OS was calculated from end of SBRT to date of death or last follow-up (FU). BRFS was calculated from end of SBRT to date of biochemical failure or most recent PSA. OS and BRFS were estimated using Kaplan-Meier methodology with comparisons accomplished using log-rank statistics. Median FU is 58 months. Median initial PSA is 6.2 (range 1.3-62). Median PSA nadir is 0.14 with interquartile range of 0.10 to 0.40. Nine-year actuarial OS is 78.3%. No significant differences in OS are observed between risk groups or other prognostic/treatment factors. Eight-year actuarial BRFS is 86%. Significant differences in BRFS are observed between GS (p=0.0003), with a 7-year BRFS of 100% for GS 3+3/3+4 versus 60.5% for GS 4+3/4+4. BRFS is significantly higher for those with favorable intermediate risk with 7-year BRFS of 100% compared with 78.2% for unfavorable intermediate and high risk prostate cancer (p=0.0425). Significant differences are also noted in BRFS with 100% for high dose (37.5Gy) versus 84.9% for intermediate dose (36.25Gy) at 7 years (p=0.009). Too few patients are treated with 35Gy (n=2) for 7-year estimates. Multivariable analysis reveals GS as the sole predictor (p=0.0144) of BRFS, with 93% decreased risk for failure for GS 3+3/3+4 compared with GS 4+3/4+4. Cumulative incidence of late RTOG grade 3 urinary toxicity is 5%. Cumulative incidence of late RTOG grade 3 bowel toxicity is 1%. Eight percent of men with no erectile dysfunction at presentation developed erections insufficient for intercourse most of the time despite use of oral medications. SBRT may be an acceptable alternative for men with intermediate and high risk prostate cancer. Gleason score is the single most important independent factor for BRFS. Outcome for favorable intermediate risk prostate cancer is excellent however unfavorable intermediate prostate cancer behaves like high risk disease. Further study regarding the benefit of higher doses of radiation, in particular for high risk patients, should be explored.

Risk factors for late bowel and bladder toxicities in NRG Oncology prostate cancer trials of high-risk patients: A meta-analysis of physician-rated toxicities

PurposeA meta-analysis of sociodemographic variables and their association with late (>180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level >20) prostate cancer. Methods and materialsThree NRG trials (RTOG 9202, RTOG 9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity Scale. After controlling for study, age, Karnofsky Performance Status, and year of accrual, sociodemographic variables were added to the model for each outcome variable of interest in a stepwise fashion using the Fine-Gray regression models with an entry criterion of 0.05. ResultsA total of 2432 patients were analyzed of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced late grade ≥2 bowel and bladder toxicities, respectively, and 2% and 3% experienced late grade ≥3 bowel and bladder toxicities, respectively. Late grade ≥2 clustered bowel and bladder toxicities were seen in approximately 1% of patients and late grade ≥3 clustered toxicities were seen in 2 patients (<1%). The multivariate analysis showed that patients who received prostate-only RT+HT had a lower risk of experiencing grade ≥2 bowel toxicities than those who received whole-pelvic RT+long-term (LT) HT (hazard ratio: 0.36; 95% confidence interval, 0.18-0.73; P = .0046 and hazard ratio: 0.43; 95% confidence interval, 0.23-0.80; P = .008, respectively). Patients who received whole-pelvic RT had similar chances of having grade ≥2 bowel or bladder toxicities no matter whether they received LT or short-term HT. ConclusionsPatients with high-risk prostate cancer who receive whole-pelvic RT+LT HT are more likely to have a grade ≥2 bowel toxicity than those who receive prostate-only RT. LT bowel and bladder toxicities were infrequent. Future studies will need to confirm these findings utilizing current radiation technology and patient-reported outcomes.

Salvage Carbon Ion Radiation Therapy for Locally Recurrent or Radiation-Induced Second Primary Sarcoma of the Head and Neck.

Purpose: Salvage radiation therapy (RT) is a potentially curative treatment option for head and neck sarcomas (HNS) that did not respond to previous treatment(s). We report the first clinical experience of carbon ion radiotherapy (CIRT) for salvage treatment of locally recurrent (LR) or RT-induced secondary HNS after surgery and/or radiotherapy.Methods and Materials: A retrospective analysis of the ongoing prospective data registries from the Shanghai Proton and Heavy Ion Center was conducted. Patients with LR-HNS who underwent surgery and/or RT and those with RT-induced second primary HNS were included. Acute and late toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation toxicity scoring system, respectively. The actuarial 12-month local progression-free and overall survival rates (LPFS and OS) were calculated using the Kaplan-Meier method.Results: Between 10/2015 and 7/2017, 19 consecutive and non-selected patients with LR-HNS or RT-induced secondary HNS received definitive doses of CIRT delivered with pencil beam scanning technology for salvage. Six patients had locally recurrent soft-tissue sarcoma, and another 6 had chondrosarcoma. Among these 12 patients, 4 had received one prior course of RT. Seven additional patients had an RT-induced second primary soft tissue sarcoma (STS)/osteosarcoma after RT. The median time between the completion of initial treatment (either surgery only or surgery followed by adjuvant RT) and salvage CIRT was 30.6 months.The median follow-up time was 13.1 (range 1.6-41.1) months. All patients except one (for re-irradiation) completed the planned CIRT for salvage. The median dose of salvage CIRT was 60 GyE. Three patients developed local progression, and another 3 developed distant metastasis after salvage CIRT. Deaths occurred (3 patients) only in patients with radiation-induced second primary sarcoma at the time of analysis. The actuarial 12-month LPFS, DMFS and OS rates were 74.6%, 82.6% and 86.5%, respectively.Two patients irradiated for a second primary sarcoma had Grade 4 bleeding during CIRT, including one who experienced the rupture of an optic artery aneurysm unrelated to his disease or the salvage treatment. No patient had Grade 5 toxicity during treatment. Except for one patient who died of hemorrhage 3.5 months after the completion of CIRT, no moderate or severe late toxicities were observed.Conclusions: With few observed acute and late toxicities, salvage CIRT can provide effective short-term tumor control. Further research, preferably in a prospective fashion, will be required to confirm the efficacy and safety of salvage CIRT in this patient population.

Phase 1/2 Dose-Escalation Study of the Use of Intensity Modulated Radiation Therapy to Treat the Prostate and Pelvic Nodes in Patients With Prostate Cancer

PurposeTo investigate the feasibility of dose escalation and hypofractionation of pelvic lymph node intensity modulated radiation therapy (PLN-IMRT) in prostate cancer (PCa).Methods and MaterialsIn a phase 1/2 study, patients with advanced localized PCa were sequentially treated with 70 to 74 Gy to the prostate and dose-escalating PLN-IMRT at doses of 50 Gy (cohort 1), 55 Gy (cohort 2), and 60 Gy (cohort 3) in 35 to 37 fractions. Two hypofractionated cohorts received 60 Gy to the prostate and 47 Gy to PLN in 20 fractions over 4 weeks (cohort 4) and 5 weeks (cohort 5). All patients received long-course androgen deprivation therapy. Primary outcome was late Radiation Therapy Oncology Group toxicity at 2 years after radiation therapy for all cohorts. Secondary outcomes were acute and late toxicity using other clinician/patient-reported instruments and treatment efficacy.ResultsBetween August 9, 2000, and June 9, 2010, 447 patients were enrolled. Median follow-up was 90 months. The 2-year rates of grade 2+ bowel/bladder toxicity were as follows: cohort 1, 8.3%/4.2% (95% confidence interval 2.2%-29.4%/0.6%-26.1%); cohort 2, 8.9%/5.9% (4.1%-18.7%/2.3%-15.0%); cohort 3, 13.2%/2.9% (8.6%-20.2%/1.1%-7.7%); cohort 4, 16.4%/4.8% (9.2%-28.4%/1.6%-14.3%); cohort 5, 12.2%/7.3% (7.6%-19.5%/3.9%-13.6%). Prevalence of bowel and bladder toxicity seemed to be stable over time. Other scales mirrored these results. The biochemical/clinical failure–free rate was 71% (66%-75%) at 5 years for the whole group, with pelvic lymph node control in 94% of patients.ConclusionsThis study shows the safety and tolerability of PLN-IMRT. Ongoing and planned phase 3 studies will need to demonstrate an increase in efficacy using PLN-IMRT to offset the small increase in bowel side effects compared with prostate-only IMRT.

Proton Beam Radiation for Head and Neck Cancers: A Single-Institution Report on Feasibility and Early Outcomes

Definitive radiation of the head and neck has become a mainstay for locally advanced head and neck malignancies. This combined with initial surgery and/or adjuvant chemotherapy yields significant morbidity to the patients both short term and long term. This is a review of our prospective registry database of head and neck patients treated with proton beam radiation at our hybrid community practice/academic proton center to highlight our initial experience with relative long term follow up. All patients in our study were treated with the uniform scanning proton beam technology via the IBA system. Standard fractionation schemes with or without chemotherapy were delivered with curative intent. Acute and late toxicities were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the by the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure (LRF) was calculated with death as a competing risk. The actuarial freedom from distant metastases (FFDM) and overall survival (OS) rates were calculated with the Kaplan-Meier method. A total of 66 patients were analyzed from our prospective registry. We focused on the 36 de-novo patients as our 30 re-irradiation patients are in process in upcoming literature. The scope of our patient population included patients with malignancies of the paranasal sinuses, nasopharynx, oropharynx, hypopharynx, and major salivary gland. Squamous Cell Carcinoma was the predominant histology, but others were Mucoepidermoid Carcinoma, Adenoid Cystic Carcinoma, Undifferentiated Carcinomas and Esthesioneuroblastomas. The median follow up was 33 months (9 – 53). The 2 and 5 year OS rates were 83% and 75%, respectively. The 2 and 5 year FFDM rates were 92% and 80%, respectively. There was 17% and 25% 2 and 5 year LRF rate. The mean time to failure was 17 months post initial proton beam treatment. Acute grade 3+ toxicity rate was 30.5% (mainly skin, mucositis, odynophagia, dysphagia, and anorexia), while the long term grade 3+ toxicity rate was 6% (anorexia and dysphagia). Ten patients had feeding tubes at some point during the radiation therapy, but none remained on tube feedings beyond 6 months post proton radiation therapy. Proton beam radiation of the head and neck can provide excellent disease control along with great sparing of the OARs. Longer follow up is needed with a less heterogeneous population to validate this modality. In addition, with the advent of intensity modulated proton beam radiation, even better conformality of proton beam will hopefully improve the toxicity profiles of even the acute toxicities.

Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes

Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study.

The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]10 = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.

Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

BackgroundTo investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC).Material and Methods205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68–70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.ResultsThe median follow-up period was 37.3 months (range, 6.3–45.1 months). The 3-year estimated local failure–free survival, regional failure–free survival, locoregional failure–free survival, distant metastasis–free survival, disease–free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2–3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively.ConclusionsVMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

External beam radiation therapy in treatment of malignant pheochromocytoma and paraganglioma.

Purpose: Pheochromocytomas (PCCs) are neuroendocrine tumors arising from the adrenal medulla or as paraganglioma (PGL) from extra-adrenal sites. While usually benign, a small fraction is malignant. Multi-modality therapy is used in treating malignant disease; however, little data exist on the role of external beam radiation therapy (EBRT). In this retrospective review, we assessed response to EBRT in malignant PCCs or PGLs.Methods and Materials: Records of patients treated at the National Institutes of Health who received EBRT between 1990 and 2012 were studied. Patients were assessed for symptomatic control, biochemical response, local and distant control by response evaluation criteria in solid tumors v1.1 or stable disease on imaging reports, toxicity by radiation therapy oncology group (RTOG) criteria, and survival.Results: There were 24 patients treated who received EBRT to lesions of the abdomen (n = 3), central nervous system (n = 4), and bone (n = 40). Lesions were treated with 3D conformal EBRT to a mean dose of 31.8 Gy in 3.3 Gy fractions, or fractionated stereotactic radiosurgery to 21.9 Gy in 13.6 Gy fractions. Patients experienced acute (n = 15) and late (n = 2) RTOG toxicities; no patient experienced acute toxicity ≥4 or late toxicity ≥2. Symptomatic control was achieved in 81.1% of lesions. Stable radiographic response was achieved in 86.7% of lesions with progression in 13%. Distant progression was observed overall in 75% of patients and average survival was 52.4 months.Conclusion: Malignant PCC and PGL often do not respond well to current systemic therapies. In these cases, EBRT can be considered in patients with symptomatic, localized disease progression.

Commentary on “Toxicity after external beam radiotherapy for prostate cancer: An analysis of late morbidity in men with diabetes mellitus.” Kalakota K, Liauw SL, Department of Radiation Oncology, Northwestern Memorial Hospital, Chicago, IL.: Urology 2013;81(6):1196–201. doi: 10.1016/j.urology.2013.01.047. [Epub 2013 Mar 26

ObjectiveTo investigate the influence of diabetes mellitus (DM) on late genitourinary (GU) and gastrointestinal (GI) toxicity in patients treated with external beam radiotherapy (RT) for prostate cancer. Materials and methodsA total of 626 men were treated with curative-intent RT for prostate cancer from 1988 to 2008. Using the National Comprehensive Cancer Network risk category, the patients were considered to have low-risk (30%), intermediate-risk (42%), or high-risk (28%) prostate cancer. The median radiation dose was 74Gy; 45% received androgen deprivation therapy for a median of 4 months. Late GU and GI Radiation Therapy Oncology Group toxicity was recorded prospectively at each visit after external beam RT. The median follow-up period was 55 months. ResultsOf the 626 men, 102 (16%) had DM that was controlled by diet (8%), oral medications (52%), or insulin (39%). The patients with DM were more likely to receive intensity-modulated RT and androgen deprivation therapy and to have a shorter follow-up duration (P≤.05 for all). Univariate analyses demonstrated that greater radiation dose, baseline urinary dysfunction, intensity-modulated RT, and DM were associated with grade 2 or greater GU toxicity, and transurethral resection of the prostate and DM were associated with grade 3 or greater GU toxicity. In addition, androgen deprivation therapy use, age≥70 years, and anticoagulation were associated with grade 2 or greater GI toxicity, and age≥70 years and anticoagulation were associated with grade 3 or greater GI toxicity. The multivariate analyses for late toxicity demonstrated a greater risk of grade 2 or greater (relative risk 1.36, P = .10) and grade 3 or greater GU toxicity (relative risk 2.74, P = .04) with DM. ConclusionA greater incidence of late GU toxicity was seen in patients with DM treated for prostate cancer. This relationship might be useful when considering the treatment of patients with DM, especially those receiving dose-escalated RT or with a history of transurethral resection of the prostate.

Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer

ObjectiveTo assess the toxicity of delivering extended field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for locally advanced cervical carcinoma.MethodsForty-five patients who underwent EF-IMRT and concurrent cisplatin chemotherapy for the treatment of stage IB2 to IIIB cervical cancer were retrospectively reviewed. The clinical target volume included all areas of gross and potentially microscopic disease and regional lymph node regions. All patients underwent high-dose-rate brachytherapy. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively.ResultsThe median follow-up was 28 months (range, 5 to 62 months). Forty-two patients had a complete response, and three had a persistent disease. Of those 42 patients, 15 patients (35.7%) had recurrence. The regions of recurrence were in-field in 2 patients and out-field in 13 patients. Acute grade ≥3 gastrointestinal, genitourinary and hematologic toxicity occurred in 3, 1, and 9 patients, respectively. Three patients (6.7%) suffered from late grade 3 toxicities. Seven patients experienced ovarian transposition, 5 of those patients (71%) maintained ovarian function. Thirty-eight patients (84.4%) were alive at the last follow-up.ConclusionConcurrent cisplatin chemotherapy with EF-IMRT was safe. The acute and late toxicities are acceptable. EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

Five-year outcome of concurrent radiotherapy and chemotherapy in Saudi women with locally advanced cervical cancer: single-institution experience

BACKGROUND AND OBJECTIVESWe aimed to evaluate long-term treatment outcomes and toxicity profile of combined radiotherapy and chemotherapy in Saudi women with locally advanced cervical cancer.DESIGN AND SETTINGSRetrospective study in a tertiary care cancer center in Riyadh, Saudi Arabia.METHODS AND MATERIALSThe medical records of patients with histopathologically proven, locally advanced cervical cancer were analyzed. These patients received three-dimensional conformal radiotherapy with concurrent chemotherapy followed by high dose rate brachytherapy in our center between July 2007 and April 2012. The data regarding the safety profile, response rates, occurrence of locoregional or distant failure, disease-free survival, and overall survival rates were recorded.RESULTSThe median follow-up period was 60 months (range, 8–66) for 74 patients. The median age of study population was 52.3 years (32–78), and the stage IIB was the predominant stage (49 patients [66.2%]). A total of 45 patients (60.9%) had radiologic-positive pelvic ± para-aortic lymphadenopathy. The 5-year locoregional and distant control rates were 84.3% and 78.5%, respectively. The 5-year disease-free and overall survival rates were 75.7% and 64.5%, respectively. Stage, nodal status, and hemoglobin levels were found to be important prognostic factors for locoregional and distant control. Acute grade 3 hematological and nonhematological toxicities were seen in 4 (5.4%) and 4 (5.4%) patients. Late toxicities were mild, and only 1 (1.4%) patient presented with subacute intestinal obstruction.CONCLUSIONConcurrent chemoradiation in Saudi women with locally advanced cervical cancer showed better locoregional and distant control and survival rates with minimal toxicity.

Toxicity After External Beam Radiotherapy for Prostate Cancer: An Analysis of Late Morbidity in Men With Diabetes Mellitus

To investigate the influence of diabetes mellitus (DM) on late genitourinary (GU) and gastrointestinal (GI) toxicity in patients treated with external beam radiotherapy (RT) for prostate cancer. A total of 626 men were treated with curative-intent RT for prostate cancer from 1988 to 2008. Using the National Comprehensive Cancer Network risk category, the patients were considered to have low-risk (30%), intermediate-risk (42%), or high-risk (28%) prostate cancer. The median radiation dose was 74 Gy; 45% received androgen deprivation therapy for a median of 4 months. Late GU and GI Radiation Therapy Oncology Group toxicity was recorded prospectively at each visit after external beam RT. The median follow-up period was 55 months. Of the 626 men, 102 (16%) had DM that was controlled by diet (8%), oral medications (52%), or insulin (39%). The patients with DM were more likely to receive intensity-modulated RT and androgen deprivation therapy and to have a shorter follow-up duration (P≤.05 for all). Univariate analyses demonstrated that greater radiation dose, baseline urinary dysfunction, intensity-modulated RT, and DM were associated with grade 2 or greater GU toxicity, and transurethral resection of the prostate and DM were associated with grade 3 or greater GU toxicity. In addition, androgen deprivation therapy use, age≥70 years, and anticoagulation were associated with grade 2 or greater GI toxicity, and age≥70 years and anticoagulation were associated with grade 3 or greater GI toxicity. The multivariate analyses for late toxicity demonstrated a greater risk of grade 2 or greater (relative risk 1.36, P= .10) and grade 3 or greater GU toxicity (relative risk 2.74, P=.04) with DM. A greater incidence of late GU toxicity was seen in patients with DM treated for prostate cancer. This relationship might be useful when considering the treatment of patients with DM, especially those receiving dose-escalated RT or with a history of transurethral resection of the prostate.

Outcomes for Patients With Cervical Cancer Treated With Extended-Field Intensity-Modulated Radiation Therapy and Concurrent Cisplatin

To evaluate disease outcomes and toxicity in patients with cervical cancer treated with extended-field intensity-modulated radiotherapy. We included all patients treated with extended-field intensity-modulated radiotherapy and concurrent weekly cisplatin from 2003 to 2010 at 2 institutions. Overall survival and disease-free survival were estimated using Kaplan-Meier method. Locoregional failure (LRF), distant failure, and competing mortality were calculated using cumulative incidence functions. Acute and late toxicity were graded using Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. The study included 21 patients, 14 and 20 of which had positive para-aortic and pelvic nodes, respectively. The median follow-up was 22 months. Eighteen-month overall survival and disease-free survival were 59.7% (95% confidence interval [CI], 41.2%-86.4%) and 42.9% (95% CI, 26.2%-70.2%). Eighteen-month cumulative incidences of LRF, distant failure, and competing mortality were 9.5% (95% CI, 1.5-26.8%), 42.9% (95% CI, 21.3-62.9%), and 4.8% (95% CI, 0.3-20.2%), respectively. Eighteen-month cumulative incidences of late grade 3 or higher-grade genitourinary and gastrointestinal toxicity were 4.8% (95% CI, 0.2%-20.3%) and 0%, respectively. Intensity-modulated extended-field radiotherapy was associated with low rates of late toxicity and LRF. High rates of distant failure indicate that this group of patients could benefit from intensified systemic therapy.

Extended-Field Intensity-Modulated Radiotherapy and Concurrent Cisplatin-Based Chemotherapy for Postoperative Cervical Cancer With Common Iliac or Para-Aortic Lymph Node Metastases: A Retrospective Review in a Single Institution

Retrospectively, to assess the toxicity of delivering postoperative extended-field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for patients with cervical cancer with a pathologically confirmed positive common iliac node and/or a para-aortic node. Each patient received postoperative EF-IMRT and concurrent cisplatin chemotherapy. The clinical target volume included regional lymph node regions (obturator; common, internal, and external iliac nodal regions; presacral region; and para-aortic regions) and the upper 2.0 cm of the vagina and paravaginal soft tissue lateral to the vagina. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events (CTCAE) and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. Fifty-eight patients were treated with postoperative EF-IMRT and concurrent cisplatin chemotherapy. The median follow-up was 34 months. Eighteen patients (31%) had recurrence. The region of recurrence was in-field in 2 patients (3.4%) and out-field in 16 patients (27.6%). Acute grade 3 or higher gastrointestinal, genitourinary, and hematologic toxicity occurred in 2, 1, and 11 patients, respectively. Three patients (5.1%) had late grade 3 toxicities. Thirteen patients experienced ovarian transposition; of these, 10 patients (77%) maintained ovarian function. Forty-one patients (71%) were alive at the last follow-up. Concurrent cisplatin chemotherapy with postoperative EF-IMRT was safe and well tolerated. The acute and late toxicities are acceptable. The locoregional control rates are hopeful, although distant metastases continue to be the primary mode of failure. Postoperative EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

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.