"Just One More Rep!" - Ability to Predict Proximity to Task Failure in Resistance Trained Persons.

In resistance training, the use of predicting proximity to momentary task failure (MF, i.e., maximum effort), and repetitions in reserve scales specifically, is a growing approach to monitoring and controlling effort. However, its validity is reliant upon accuracy in the ability to predict MF which may be affected by congruence of the perception of effort compared with the actual effort required. The present study examined participants with at least 1 year of resistance training experience predicting their proximity to MF in two different experiments using a deception design. Within each experiment participants performed four trials of knee extensions with single sets (i.e., bouts of repetitions) to their self-determined repetition maximum (sdRM; when they predicted they could not complete the next repetition if attempted and thus would reach MF if they did) and MF (i.e., where despite attempting to do so they could not complete the current repetition). For the first experiment (n = 14) participants used loads equal to 70% of a one repetition maximum (1RM; i.e., the heaviest load that could be lifted for a single repetition) performed in a separate baseline session. Aiming to minimize participants between day variability in repetition performances, in the second separate experiment (n = 24) they used loads equal to 70% of their daily isometric maximum voluntary contraction (MVC). Results suggested that participants typically under predicted the number of repetitions they could perform to MF with a meta-analytic estimate across experiments of 2.0 [95%CIs 0.0 to 4.0]. Participants with at least 1 year of resistance training experience are likely not adequately accurate at gauging effort in submaximal conditions. This suggests that perceptions of effort during resistance training task performance may not be congruent with the actual effort required. This has implications for controlling, programming, and manipulating the actual effort in resistance training and potentially on the magnitude of desired adaptations such as improvements in muscular hypertrophy and strength.

Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6).

AIM: To compare quality of life (QOL) between standard (SFX) chemoradiotherapy (arm A) and altered fractionation radiotherapy (AFX) with panitumumab (PMab; arm B). METHODS: Patients with T any N + M0 or T3-4N0M0 squamous cell head-neck carcinoma were randomised to SFX (70 Gy/35/7 wks) plus cisplatin (100 mg/m2 IV × 3) versus AFX (70 Gy/35/6 wks) plus PMab (9 mg/kg IV × 3). QOL was collected at baseline, end of radiation therapy (RT) and 2, 4, 6, 12, 24 and 36 months post-RT using the Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N), MD Anderson Dysphagia Index (MDADI) and SWAL-QOL. We hypothesised a 6-point more favourable change in FACT-H&N score from baseline to 1 year in arm B over arm A. RESULTS: Among 320 patients, median follow-up was 46 (range: 0.1-64.3) months, median age 56, 84% male, Eastern Cooperative Oncology Group PS 0 (71%), 1 (29%). Primary site was oropharynx in 81% (p16+ 68%, p16- 16%, missing 16%). Baseline scores did not differ by arm (A/B): FACT-H&N 116.5/115, MDADI Global 83/77, SWAL-QOL General 67/68. At 1 year, no difference was seen between arms in FACT-H&N change from baseline: A -1.70, B -4.81, p = 0.194. Subscale change scores by arm were (A/B): last week RT, FACT-Physical (-11.6, -10, p = 0.049), MDADI Physical (-40.4, -33.9, p = 0.045), and SWAL-QOL Eating Duration (-61.2, -51.2, p = 0.02), Eating Desire (-53.3, -43.9, p = 0.031) and Mental Health (-42, -32.6, p = 0.009); 4 months, HN subscale (-7.7, -10, p = 0.014). No clinically important differences by arm were seen post-treatment. CONCLUSIONS: PMab with AFX did not durably improve QOL or swallowing as compared with SFX with cisplatin. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00820248.

Evaluation of unified intensity-modulated arc therapy for the radiotherapy of head-and-neck cancer.

PURPOSE: Recently our group developed a unified intensity-modulated arc therapy (UIMAT) technique which allows for the simultaneous inverse-optimization and the combined delivery of volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). The aim of this study was to evaluate the dosimetric benefits of UIMAT plans for radiation treatment of complex head-and-neck cancer cases. METHODS AND MATERIALS: A retrospective treatment planning study was performed on 30 head-and-neck cases, 15 of which were treated clinically with VMAT while the other 15 were treated with step-and-shoot IMRT. These cases were re-planned using our UIMAT technique and the results were compared with the clinically delivered plans. Plans were assessed in terms of clinically relevant metrics describing target volume coverage, dose conformity, and the sparing of organs at risk. RESULTS: When compared to stand-alone VMAT or IMRT, UIMAT plans offered slightly better tumor volume coverage (Median D95: 98.1% vs. 97.5%, p=0.01) and similar dose conformity (Median CI: 0.69 vs. 0.69, p=0.09). More significantly, UIMAT plans had substantially lower doses to all organs at risk, including the spinal cord (Median D2%: 29.9Gy vs. 35.6Gy, p<0.01), brainstem (Median D2%: 21.2Gy vs. 25.6Gy, p<0.01), left parotid (Median DMean: 26.1Gy vs. 28.0Gy, p<0.01), and right parotid (Median DMean: 23.6Gy vs. 27.2Gy, p<0.01). The reduction in OAR doses did not result from the redistribution of dose to unspecified tissue. Furthermore, UIMAT plans can be delivered with comparable delivery times to VMAT (Median time: 135s vs. 168s, p=0.394) but with fewer monitor units (Median MU: 486 vs. 635, p<0.01). CONCLUSIONS: Compared to stand-alone IMRT or VMAT, UIMAT was demonstrated to have a dosimetric advantage for the radiation treatment of head-and-neck cancer.

Detection of circulating tumor cells in advanced head and neck cancer using the CellSearch system.

BACKGROUND: Early detection of circulating tumor cells (CTCs) offers the possibility of improved outcome for patients with head and neck squamous cell cancer (HNSCC). METHODS: Patients with advanced-stage HNSCC (stage III/IV) were tested for CTCs using the CellSearch system (a registered trade name), which has been approved by the U.S. Food and Drug Administration (FDA) for monitoring CTCs in other cancers. RESULTS: CTCs were detected in 6 of 15 patients with advanced-stage HNSCC (range, 1-2 cells/7.5 mL of blood). CTCs were significantly associated with patients with lung nodules >1 cm (p = .04). There was also a suggestion of improved survival in the CTC-negative versus the CTC-positive patients (p = .11). CONCLUSIONS: CTCs can be successfully isolated in patients with advanced-stage HNSCC using the CellSearch system. CTC detection may be important for prognosis, evaluating treatment outcome, and for determining efficacy of adjuvant treatments.

Evaluation of tomotherapy MVCT image enhancement program for tumor volume delineation.

The aims of this study were to investigate the variability between physicians in delineation of head and neck tumors on original tomotherapy megavoltage CT (MVCT) studies and corresponding software enhanced MVCT images, and to establish an optimal approach for evaluation of image improvement. Five physicians contoured the gross tumor volume (GTV) for three head and neck cancer patients on 34 original and enhanced MVCT studies. Variation between original and enhanced MVCT studies was quantified by DICE coefficient and the coefficient of variance. Based on volume of agreement between physicians, higher correlation in terms of average DICE coefficients was observed in GTV delineation for enhanced MVCT for patients 1, 2, and 3 by 15%, 3%, and 7%, respectively, while delineation variance among physicians was reduced using enhanced MVCT for 12 of 17 weekly image studies. Enhanced MVCT provides advantages in reduction of variance among physicians in delineation of the GTV. Agreement on contouring by the same physician on both original and enhanced MVCT was equally high.

Pain and symptom assessment during multiple fractions of gynecologic high-dose-rate brachytherapy.

PURPOSE: A prospective assessment of tolerability of gynecologic brachytherapy was completed to determine adequacy of analgesia and symptom control for patients undergoing CT-guided brachytherapy, with multiple fractions delivered during a single applicator insertion. METHODS AND MATERIALS: Seventeen patients receiving high-dose-rate brachytherapy for gynecologic cancer (other than vaginal vault) completed ratings of pain intensity, anxiety, and nausea at five key time points before, during, and after brachytherapy. Symptoms were assessed with patient-reported scores using an 11-point numeric rating scale. The patient population included cervical (n=12), endometrial (n=3), and vulvar-vaginal (n=2) malignancies. Patients underwent general anesthesia for applicator placement. Analgesia consisted of subcutaneous route opioid, and oral opioid and/or nonopioid as needed for the duration of the treatment planning and delivery. RESULTS: The mean scores for pain were highest after patients were transferred to the CT scanner, 3.3±2.6, compared with baseline scores of 0.9±1.7. Pain scores were 2.3±2.3 during the remainder of the procedure, and 2.7±2.1 after the removal of the applicator. The highest mean anxiety scores occurred before the brachytherapy procedure, 4.3±3.4, with resolution of anxiety during the procedure to 1.3±1.6. The mode of nausea scoring during the procedure was 0. CONCLUSION: For most of the patients, the delivery of multiple fractions of image-guided high-dose-rate brachytherapy is well tolerated with maximum scores of mild-moderate pain and distress, and no significant nausea. This can be accomplished with applicator placement under general anesthesia and standard medical management.

The N3 neck: outcomes following primary chemoradiotherapy.

OBJECTIVE: To study the treatment outcomes of N3 neck disease following primary chemoradiotherapy. DESIGN: Retrospective cohort. SETTING: Tertiary care centre. METHODS: A review was conducted of 25 consecutive patients with N3 neck disease treated with primary platinum-based chemoradiotherapy. A neck dissection (ND) was offered in the event of clinical and/or radiologic evidence of residual disease on follow-up. MAIN OUTCOME MEASURES: Recurrence-free, disease-specific, and overall survival and patterns of failure. RESULTS: A regional complete response (CR) was noted in 48% of the patients. ND was performed in 36% of the cases. The median duration between the end of radiation and ND was 71 days. The recurrence-free survival rates at 1 and 2 years were 73% and 64%, respectively. The 2-, 3-, and 5-year overall survival rates were 66.7%, 52%, and 31.2%, respectively. Disease-specific survival rates were 69.6%, 63.3%, and 50.6%, respectively. Nine patients developed distant recurrence, with one having concurrent local and regional recurrence as well. Patients in the CR group remained free of regional recurrence. Among the initial partial responders, 54% eventually developed distant metastasis compared to 17% in the CR group. CONCLUSION: Patients with N3 disease may be managed with chemoradiotherapy, with ND reserved for salvage. Distant metastasis accounts for most recurrences and for the reduction in survival.

Phase I trial of simultaneous in-field boost with helical tomotherapy for patients with one to three brain metastases.

PURPOSE: Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. METHODS AND MATERIALS: The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. RESULTS: A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. CONCLUSION: The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.

An early report on outcomes from computed tomographic-based high-dose-rate brachytherapy for locally advanced cervix cancer: A single institution experience.

PURPOSE: To report our experience using high-dose-rate (HDR) brachytherapy with computed tomographic (CT) imaging for locally advanced cervix cancer, using available resources to optimize the treatment. METHODS AND MATERIALS: Fifty-seven women with cervix cancer were treated between September 2004 and March 2008. Patients received external radiotherapy, HDR brachytherapy (7 Gy x4) and concurrent chemotherapy. CT planning was done for each insertion. RESULTS: Median age was 53 years (range, 29-89 years); majority (49%) had International Federation of Gynecology and Obstetrics stage IIB. The median follow-up was 22.6 months. There were 4 patients who required laser coagulation for rectal bleeding, and one patient required hemicolectomy for sigmoid stricture. There was no grade 3 or 4 genitourinary toxicity. The Kaplan-Meier overall survival, relapse free, central pelvic and pelvic control at 3 years was 86%, 62%, 89%, and 83%, respectively. Pelvic control for tumors 2 to 5 cm was 95% and 84% for tumors greater than 5 cm. CONCLUSIONS: Our early experience confirms that CT-based HDR brachytherapy for cervix cancer achieves disease control comparable to other published series. At the same time, conformal avoidance of organs at risk allows for low rates of toxicity.

A prospective evaluation of helical tomotherapy.

PURPOSE: To report results from two clinical trials evaluating helical tomotherapy (HT). METHODS AND MATERIALS: Patients were enrolled in one of two prospective trials of HT (one for palliative and one for radical treatment). Both an HT plan and a companion three-dimensional conformal radiotherapy (3D-CRT) plan were generated. Pretreatment megavoltage computed tomography was used for daily image guidance. RESULTS: From September 2004 to January 2006, a total of 61 sites in 60 patients were treated. In all but one case, a clinically acceptable tomotherapy plan for treatment was generated. Helical tomotherapy plans were subjectively equivalent or superior to 3D-CRT in 95% of plans. Helical tomotherapy was deemed equivalent or superior in two thirds of dose-volume point comparisons. In cases of inferiority, differences were either clinically insignificant and/or reflected deliberate tradeoffs to optimize the HT plan. Overall imaging and treatment time (median) was 27 min (range, 16-91 min). According to a patient questionnaire, 78% of patients were satisfied to very satisfied with the treatment process. CONCLUSIONS: Helical tomotherapy demonstrated clear advantages over conventional 3D-CRT in this diverse patient group. The prospective trials were helpful in deploying this technology in a busy clinical setting.

Sentinel node biopsy as an adjunct to limb salvage surgery for epithelioid sarcoma of the hand.

BACKGROUND: Epithelioid sarcomas of the hand are rare, high-grade tumors with a propensity for regional lymphatic spread approaching 40%. CASE PRESENTATION: A 54-year-old male with an epithelioid sarcoma of the palm was treated with neoadjuvant radiation, wide excision, and two-stage reconstruction. Sentinel lymph node biopsy was used to stage the patient's axilla. Sentinel node biopsy results were negative. The patient has remained free of local, regional and distant disease for the follow-up time of 16 months. CONCLUSION: The rarity of this tumor makes definitive conclusions difficult but SLN biopsy appears to be a useful adjunct in the treatment of these sarcomas.

Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma.

BACKGROUND AND PURPOSE: This study compared late radiation morbidity in patients with extremity soft tissue sarcoma randomized to treatment by pre- (50 Gy) or postoperative (66 Gy) radiotherapy in combination with surgery. The morbidities evaluated included fibrosis, joint stiffness and edema at 2 years following treatment. The impact of morbidity on patient function as measured by the Musculoskeletal Tumor Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS) was also evaluated. PATIENTS AND METHODS: 129 patients were evaluated. Toxicity rates were compared by treatment arm using the Fisher's exact test. Function scores by toxicity were analyzed using the Wilcoxon rank sum test. Multivariate logistic regression was used to evaluate the joint effect of treatment arm, field size, and dose on subcutaneous tissue fibrosis, joint stiffness and edema. RESULTS: 27 of 56 patients (48.2%) in the postoperative arm compared to 23 of 73 (31.5%) in the preoperative arm had grade 2 or greater fibrosis (P = 0.07). Although not statistically significant, edema was more frequent in the postoperative arm, 13 of 56 (23.2%) versus 11 of 73 (15.5%) in the preoperative arm, as was joint stiffness, 13 of 56 (23.2%) versus 13 of 73 (17.8%). Patients with significant fibrosis, joint stiffness or edema had significantly lower function scores on both measures (all P-values < 0.01). Field size was predictive of greater rates of fibrosis (P = 0.002) and joint stiffness (P = 0.006) and marginally predictive of edema (P = 0.06). CONCLUSIONS: Patients treated with postoperative radiotherapy tended to have greater fibrosis. Fibrosis, joint stiffness and edema adversely affect patient function.