Selective omission of level V nodal coverage for patients with oropharyngeal cancer: Clinical validation of intensity-modulated radiotherapy experience and dosimetric significance.

BACKGROUND: We sought to validate the consensus recommendation and assess dosimetric significance of selective omission of nodal level V from intensity-modulated radiotherapy (IMRT) clinical target volume (CTV) for oropharyngeal cancer. METHODS: IMRT plans and clinical outcomes for 112 patients with oropharyngeal cancer (nodal classification N0-N2b) were analyzed for coverage of ipsilateral and contralateral nodal level V. Additionally, new IMRT plans were generated in 6 randomly selected patients to assess its dosimetric impact. RESULTS: With median follow-up of 3.4 years, there were no failures identified in nodal level V with or without nodal level V omission. Upon dosimetric evaluation, significant reduction in integral dose, V10 Gy , V20 Gy , V30 Gy , V40 Gy , and V50 Gy was observed by excluding unilateral and bilateral level V from the CTV. CONCLUSION: We clinically validate the consensus recommendation for selective omission of level V nodal coverage in IMRT planning of patients with oropharyngeal cancer and demonstrate significant dosimetric advantages.

Impact of adjuvant pelvic radiotherapy in stage I uterine sarcoma.

BACKGROUND/AIM: The optimal adjuvant therapy for stage I uterine sarcoma remains unresolved and may consist of radiotherapy (RT), chemotherapy, hormonal therapy or observation. We analyzed the impact of adjuvant pelvic RT on overall survival (OS), cause-specific survival (CSS), disease-free survival (DFS), pelvic control (PC) and patterns of failure. PATIENTS AND METHODS: A retrospective analysis of 157 patients with International Federation of Gynecology and Obstetrics FIGO stage I uterine sarcoma was performed. RT was given postoperatively to a dose of 45-51 Gy in 28-30 fractions. RESULTS: The 5-year OS, CSS, DFS and PC was 58%, 62%, 47% and 72%, respectively. Adjuvant RT significantly improved PC (85% for RT group vs. 64% for non-RT group; p=0.02) but did not impact OS, CSS or DFS. CONCLUSION: The addition of adjuvant pelvic RT significantly improved PC for patients with stage I uterine sarcoma. As systemic therapies continue to improve, optimal locoregional control may result in improved patient outcomes.

Single institution experience treating 104 vestibular schwannomas with fractionated stereotactic radiation therapy or stereotactic radiosurgery.

UNLABELLED: The pupose of this study is to assess the long-term outcome and toxicity of fractionated stereotactic radiation therapy (FSRT) and stereotactic radiosurgery (SRS) for 100 vestibular schwannomas treated at a single institution. From 1993 to 2007, 104 patients underwent were treated with radiation therapy for vestibular schwannoma. Forty-eight patients received SRS, with a median prescription dose of 12.5 Gy for SRS (range 9.7-16 Gy). For FSRT, two different fraction schedules were employed: a conventional schedule (ConFSRT) of 1.8 Gy per fraction (Gy/F) for 25 or 28 fractions to a total dose of 45 or 50.4 Gy (n = 19); and a once weekly hypofractionated course (HypoFSRT) consisting of 4 Gy/F for 5 fractions to a total dose of 20 Gy (n = 37). Patients treated with FSRT had better baseline hearing, facial, and trigeminal nerve function, and were more likely to have a diagnosis of NF2. The 5-year progression free rate (PFR) was 97.0 after SRS, 90.5% after HypoFSRT, and 100.0% after ConFSRT (p = NS). Univariate analysis demonstrated that NF2 and larger tumor size (greater than the median) correlated with poorer local control, but prior surgical resection did not. Serviceable hearing was preserved in 60.0% of SRS patients, 63.2% of HypoFSRT patients, and 44.4% of ConFSRT patients (p = 0.6). Similarly, there were no significant differences in 5-year rates of trigeminal toxicity facial nerve toxicity, vestibular dysfunction, or tinnitus. CONCLUSIONS: Equivalent 5-year PFR and toxicity rates are shown for patients with vestibular schwanoma selected for SRS, HypoFSRT, and ConFSRT after multidisciplinary evaluation. Factors correlating with tumor progression included NF2 and larger tumor size.

Reirradiation for locoregionally recurrent lung cancer: outcomes in small cell and non-small cell lung carcinoma.

OBJECTIVES: To our knowledge this is the largest report analyzing outcomes for re-irradiation (reRT) for locoregionally recurrent lung cancer, and the first to assess thoracic reRT outcomes in patients with small cell lung cancer (SCLC). METHODS: Forty-eight patients (11 SCLC, 37 non-small cell lung cancer [NSCLC]) receiving reRT to the thorax were identified; 44 (92%) received reRT by intensity-modulated radiotherapy. Palliative responses, survival outcomes, and prognostic factors were analyzed. RESULTS: NSCLC patients received a median of 30 Gy in a median of 10 fractions, whereas SCLC patients received a median of 37.5 Gy in a median of 15 fractions. Median survival for the entire cohort from reRT was 4.2 months. Median survival for NSCLC patients was 5.1 months, versus 3.1 months for the SCLC patients (P=0.15). In NSCLC patients, multivariate analysis demonstrated that Karnofsky performance status≥80 and higher radiation dose were associated with improved survival following reRT, and 75% of patients with symptoms experienced palliative benefit. In SCLC, 4 patients treated with the intent of life prolongation for radiographic recurrence had a median survival of 11.7 months. However, acute toxicities and new disease symptoms limited the duration of palliative benefit in the 7 symptomatic SCLC patients to 0.5 months. CONCLUSIONS: ReRT to the thorax for locoregionally recurrent NSCLC can provide palliative benefit, and a small subset of patients may experience long-term survival. Select SCLC patients may experience meaningful survival prolongation after reRT, but reRT for patients with symptomatic recurrence and/or extrathoracic disease did not offer meaningful survival or durable symptom benefit.

Increased local failure risk with prolonged radiation treatment time in head and neck cancer treated with concurrent chemotherapy.

BACKGROUND: Prolonged radiation treatment time (RTT) in head and neck squamous cell carcinoma (HNSCC) is associated with inferior tumor control in patients treated with radiation therapy (RT) alone. However, the significance of prolonged RTT with concurrent chemotherapy is less clear. METHODS: We reviewed outcomes for 171 patients with primary HNSCC treated with curative intent RT and concurrent drug therapy from 2001 to 2009. The effects of RTT and other variables on local control and survival were analyzed. RESULTS: Patients with RTT >7 weeks had a significantly increased risk of local failure (hazard ratio [HR], 2.6; p = .018) and death (HR, 1.9 p = .035). These results retained significance even after adjustment for tumor stage (age was not significant). CONCLUSION: For patients treated with concurrent chemoradiotherapy (chemoRT), prolonged RTT may compromise tumor control as has been established in the setting of RT alone. Symptoms of patients with HNSCC undergoing definitive chemoRT should be managed aggressively to limit treatment interruptions.

Locoregional recurrence following accelerated partial breast irradiation for early-stage invasive breast cancer: significance of estrogen receptor status and other pathological variables.

BACKGROUND: Understanding risk factors for locoregional recurrence (LRR) after accelerated partial breast irradiation (APBI) can help to guide patient selection for treatment with APBI. Published findings to date have not been consistent. More data are needed as these risk factors continue to be defined. METHODS: A total of 277 women with early-stage invasive breast cancer underwent lumpectomy and were treated adjuvantly at our institution with APBI using high-dose rate brachytherapy. APBI was delivered using multicatheter interstitial brachytherapy (91 %) or single-entry catheter brachytherapy (9 %) to a dose of 32-34 Gy in 8-10 twice daily fractions. Failure patterns and risk factors for recurrence were analyzed. RESULTS: With a median follow-up of 61 months, the 5-year locoregional control rate was 94.4 %. Negative estrogen receptor (ER) status was strongly associated with LRR on multivariate analysis (p < 0.005). Lobular histology, the presence of an extensive intraductal component, and lymphovascular invasion also were significant but to a lesser degree than ER-negative status. Patients with multiple risk factors were at highest risk for LRR. Age was not significantly associated with increased risk for LRR. CONCLUSIONS: The presence of specific pathological features, particularly ER negative status, was associated with increased risk of LRR in this cohort of women treated with APBI. Further investigation is warranted to determine whether patients with adverse pathological risk factors are at higher risk of LRR after APBI than after conventional whole breast irradiation (WBI), as these same features also may place women at risk for LRR after WBI.

Acute hematologic and mucosal toxicities in head and neck cancer patients undergoing chemoradiotherapy: a comparison of 3D-CRT, IMRT, and helical tomotherapy.

IMRT and helical tomotherapy for head and neck cancer (HNC) treatment are associated with higher doses to certain non-target tissues than traditional static beam techniques. We hypothesized that this may lead to higher acute mucosal and hematologic toxicities. This analysis was limited to 178 patients receiving ≥60 Gy with concurrent weekly cisplatin. Radiation delivery used 3D-CRT in 41 patients (23%), conventional IMRT in 56 patients (31%), and helical tomotherapy in 81 patients (46%). Acute mucositis rates, weekly hematologic parameters, and ability to deliver planned chemotherapy cycles were examined for each patient during their course of chemoradiotherapy. Analysis showed patients were well balanced with regard to sex, age, and stage. Treatment time, as assessed by delivered monitor units, varied significantly between the 3D-CRT (median = 502), IMRT (median = 1087), and tomotherapy (median = 6757) cohorts. Acute mucositis grades did not significantly differ between the three subsets. Through six weeks of chemoradiotherapy, the median decline in hemoglobin was 15.6%, the median decline in platelets was 30.6%, and the median decline in leukocytes was 51.5%, but these drops were not significantly different between treatment cohorts. Chemotherapy was discontinued or held secondary to hematologic toxicity in 12% of 3D-CRT patients, 5% of IMRT patients and 15% of tomotherapy patients (p = 0.14). In conclusion, HNC patients undergoing high dose radiation with concurrent weekly cisplatin chemotherapy, the longer beam-on times and larger volumes of low-to-moderate radiation doses to non-target tissues associated with modern IMRT delivery techniques do not appear to result in increased acute hematologic or mucosal toxicities.

Early hypofractionated salvage radiotherapy for postprostatectomy biochemical recurrence.

BACKGROUND: Postprostatectomy adjuvant or salvage radiotherapy, when using standard fractionation, requires 6.5 to 8 weeks of treatment. The authors report on the safety and efficacy of an expedited radiotherapy course for salvage prostate radiotherapy. METHODS: A total of 108 consecutive patients were treated with salvage radiation therapy to 65 grays (Gy) in 26 fractions of 2.5 Gy. Median follow-up was 32.4 months. Median presalvage prostate-specific antigen (PSA) was 0.44 (range, 0.05-9.50). Eighteen (17%) patients received androgen deprivation after surgery or concurrently with radiation. RESULTS: The actuarial freedom from biochemical failure for the entire group at 4 years was 67% ± 5.3%. An identical 67% control rate was seen at 5 years for the first 50 enrolled patients, whose median follow-up was longer at 43 months. One acute grade 3 genitourinary toxicity occurred, with no acute grade 3 gastrointestinal and no late grade 3 toxicities observed. On univariate analysis, higher Gleason score (P = .006), PSA doubling time ≤12 months (P = .03), perineural invasion (P = .06), and negative margins (P = .06) showed association with unsuccessful salvage. On multivariate analysis, higher Gleason score (P = .057) and negative margins (P = .088) retained an association with biochemical failure. CONCLUSIONS: Hypofractionated radiotherapy (65 Gy in 2.5 Gy fractions in about 5 weeks) reduces the length of treatment by from 1-½ to 3 weeks relative to other treatment schedules commonly used, produces low rates of toxicity, and demonstrates encouraging efficacy at 4 to 5 years. Hypofractionation may provide a convenient, resource-efficient, and well-tolerated salvage approach for the estimated 20,000 to 35,000 US men per year experiencing biochemical recurrence after prostatectomy.

Outcomes after accelerated partial breast irradiation in patients with ASTRO consensus statement cautionary features.

PURPOSE: To evaluate outcomes among women with American Society for Radiation Oncology (ASTRO) consensus statement cautionary features treated with brachytherapy-based accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: Between March 2001 and June 2006, 322 consecutive patients were treated with high-dose-rate (HDR) APBI at the University of Wisconsin. A total of 136 patients were identified who met the ASTRO cautionary criteria. Thirty-eight (27.9%) patients possessed multiple cautionary factors. All patients received 32 to 34 Gy in 8 to 10 twice-daily fractions using multicatheter (93.4%) or Mammosite balloon (6.6%) brachytherapy. RESULTS: With a median follow-up of 60 months, there were 5 ipsilateral breast tumor recurrences (IBTR), three local, and two loco-regional. The 5-year actuarial rate of IBTR was 4.8%±4.1%. The 5-year disease-free survival was 89.6%, with a cause-specific survival and overall survival of 97.6% and 95.3%, respectively. There were no IBTRs among 32 patients with ductal carcinoma in situ (DCIS) vs. 6.1% for patients with invasive carcinoma (p=0.24). Among 104 patients with Stage I or II invasive carcinoma, the IBTR rate for patients considered cautionary because of age alone was 0% vs. 12.7% in those deemed cautionary due to histopathologic factors (p=0.018). CONCLUSIONS: Overall, we observed few local recurrences among patients with cautionary features. Women with DCIS and patients 50 to 59 years of age with Stage I/II disease who otherwise meet the criteria for suitability appear to be at a low risk of IBTR. Patients with tumor-related cautionary features will benefit from careful patient selection.

Infant and toddler oral- and manual-motor skills predict later speech fluency in autism.

BACKGROUND: Spoken and gestural communication proficiency varies greatly among autistic individuals. Three studies examined the role of oral- and manual-motor skill in predicting autistic children's speech development. METHODS: Study 1 investigated whether infant and toddler oral- and manual-motor skills predict middle childhood and teenage speech fluency; Study 2 verified those early infant and toddler predictions with historical home video; and Study 3 assessed the relation between autistic children's current-day oral-motor skill and their speech fluency. RESULTS: Infant and toddler oral-motor and manual-motor skills inter-correlated significantly, distinguished autistic children (N = 115) from typically developing children (N = 44), and distinguished autistic children whose current-day speech was minimally fluent (N = 33), moderately fluent (N = 39), and highly fluent (N = 39). These results were corroborated by analysis of historical home video (N = 32) and verified with current-day assessment (N = 40). CONCLUSIONS: The prominent associations among early oral- and manual-motor skills and later speech fluency bear implications for understanding communication in autism. For instance, these associations challenge the common assumption (made even in diagnostic criteria) that manual modes of communication are available to autistic individuals - if simply they choose to use them. These associations also highlight a potential confound from manual-motor skills when assessing autistic cognition, receptive language, and 'nonverbal' social communication.